Podcasts about BRCA1

How CD38, PARP, and Leaky Gut Are Destroying Your NAD Levels | Dr. Andrew Salzman Your NAD is being drained by two hidden enzymes, your gut may be the starting point of every aging process in your body, and creatine does something to your mitochondria that has nothing to do with muscle. This episode rewrites what you thought you knew about longevity, anti-aging biology, and how your body actually produces and delivers energy at the cellular level. -Watch this episode on YouTube for the full video experience: https://www.youtube.com/@DaveAspreyBPR -Explore all of Wonderfeel's products at: getwonderfeel.com/dave They are gifting a complimentary 7-day Youngr™ supply (mini pouch) with every order across any of their products. The code will be DAVE, and the campaign will be active through June 6th. Host Dave Asprey sits down with Dr. Andrew Salzman, a physician, inventor, and biomedical entrepreneur with more than 30 years of experience in drug discovery and development. An alumnus of Harvard Medical School, Yale University, and Columbia University, Dr. Salzman has authored more than 170 scientific publications and holds 50 patents. He invented the original clinical-stage PARP-1 inhibitor, leading to the world's first clinical treatment for raising NAD levels and fighting cancers caused by the BRCA1 and BRCA2 genes. Genentech licensed his breakthrough technology for $600 million. His research into gastrointestinal microbiota, autoimmune disease, oxidative stress, and mitochondrial ATP production now forms the foundation of how millions of patients get treated worldwide. Dr. Salzman names the two biggest NAD drains in your body, CD38 and PARP, and explains why taking NMN or NR alone is like filling a bathtub with the drain wide open. He breaks down the formulation science behind pairing NAD precursors with CD38 blockers like hydroxytyrosol alongside PARP-reducing antioxidants like ergothioneine, and delivers a paradigm-shifting explanation of creatine as an energy distribution network inside your cells. Rather than a simple muscle supplement, creatine acts as a high-speed ATP shuttle that carries energy from your mitochondria to the precise location and moment your brain, gut, and heart need it most. You'll Learn: Why NAD declines with age and which two enzymes are primarily responsible for draining it How CD38 rises with inflammation rather than NAD levels, and what that means for your supplement strategy Why creatine is one of the most underrated anti-aging and brain optimization supplements available How creatine functions as a spatial and temporal energy delivery network for your brain, gut, and heart Why the gut may be the origin point of the entire aging process and how that cascade unfolds decade by decade How leaky gut drives systemic inflammation, crashes NAD, and accelerates biological aging throughout the body What controls tight junction integrity and how ATP, butyrate, creatine, and fasting all play a role Why most creatine supplements fail to absorb properly and what to look for in a high-quality source How to rebuild your microbiome in three to four weeks through diet alone, without antibiotics Why walking immediately after a meal may be doing more harm than good to your gut lining Thank you to our sponsors! - Screenfit | Get your at-home eye training program for 40% off using code DAVE at https://www.screenfit.com/dave. - KILLSwitch | If you're ready for the best sleep of your life, order now at https://www.switchsupplements.com/and use code DAVE for 20% off - Pique | Go to Piquelife.com/dave for 20% off. - iRestore | Reverse hair loss at www.irestore.com/DAVE and get exclusive savings on the iRestore Elite, use code DAVE Dave Asprey is a four-time New York Times bestselling author, founder of Bulletproof Coffee, and the father of biohacking. With over 1,000 interviews and 1 million monthly listeners, The Human Upgrade brings you the knowledge to take control of your biology, extend your longevity, and optimize every system in your body and mind. Each episode delivers cutting-edge insights inhealth, performance, neuroscience, supplements, nutrition, biohacking, emotional intelligence, and conscious living. New episodes are released every Tuesday, Thursday, Friday, and Sunday (BONUS). Dave asks the questions no one else will and gives you real tools to become stronger, smarter, and more resilient. Keywords: Dr. Andrew Salzman, NAD depletion, CD38 inhibition, PARP inhibition, NMN supplements, creatine ATP shuttle, leaky gut aging, tight junction integrity, inflammaging, lipopolysaccharide gut, flagellin toxin, butyrate gut healing, ergothioneine, hydroxytyrosol, peroxynitrite, superoxide mitochondria, creatine energy distribution, gut origin of aging, NAD bathtub analogy, BRCA PARP inhibitor, Wonderfeel, creatine monohydrate, intestinal permeability, microbiome butyrate, selective digestive decontamination, TMAO nitric oxide Resources: • Explore all of Wonderfeel's products at: getwonderfeel.com/dave • Order Youngr™: getwonderfeel.com/dave• Order ChocoCreatin™: getwonderfeel.com/dave• Get My 2026 Clean Nicotine Roadmap | Enroll for free at https://daveasprey.com/2026-clean-nicotine-roadmap/ • Dave Asprey's Latest News | Go to https://daveasprey.com/ to join Inside Track today. • Danger Coffee: https://dangercoffee.com/discount/dave15 • My Daily Supplements: SuppGrade Labs (15% Off) • Favorite Blue Light Blocking Glasses: TrueDark (15% Off) • Dave Asprey's BEYOND Conference: https://beyondconference.com • Dave Asprey's New Book – Heavily Meditated: https://daveasprey.com/heavily-meditated • Join My Substack (Live Access To Podcast Recordings): https://substack.daveasprey.com/ • Upgrade Labs: https://upgradelabs.com Timestamps: 00:00 – Trailer 01:12 – Introduction & BRCA Background 02:19 – DNA Damage & PARP 04:38 – Free Radicals & Oxidative Stress 11:37 – NAD & Antioxidant Defense 12:34 – CD38 & NAD Depletion 23:31 – The Gut-Aging Hypothesis 30:05 – ATP, Creatine & Energy Distribution 36:41 – Creatine as Energy Shuttle 51:09 – Microbiome & Gut Repair 59:21 – TMAO & Nitric Oxide Interference 1:03:52 – Flagellin & Gut Inflammation Research 1:09:45 – FDA & Pharmaceutical Incentives 1:16:05 – Closing See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

It's common knowledge that many diseases and conditions have some kind of genetic link. But that wasn't always the case. In 1990, long before the Human Genome Project tied so many health issues to differences in genetics, researchers identified a gene called BRCA1. It was the first gene linked to a hereditary form of any common cancer. People with certain variants of BRCA1 stood a higher risk of developing breast and ovarian cancer than those without those mutations.   Geneticist Mary-Claire King and her lab were the first to identify that gene. She joined Host Flora Lichtman in September 2025 to talk about her background, her research, and her approach to science. Guest: Dr. Mary-Claire King is an American Cancer Society Professor in the departments of Genome Sciences and Medicine at the University of Washington in Seattle. Other episodes you may enjoy: A Nagasaki Survivor And Physician Recounts His Life's Work I Was Considered A Nobody Transcripts for each episode are available within 1-3 days at sciencefriday.com. Subscribe to this podcast. Follow our show on Instagram, TikTok, Facebook, and Bluesky @scifri and sign up for our newsletters. Got a science question that's keeping you up at night? Call us: 877-4-SCIFRI Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

In dieser Folge spreche ich mit Prof. Dr. Marion Kiechle, Direktorin der Frauenklinik am Klinikum rechts der Isar der TU München, und mit Daniela Maria Grob, einer mutigen Patientin, die mit Eierstockkrebs im vierten Stadium lebt und eine BRCA1-Mutation in sich trägt. Eierstockkrebs ist einer der wenigen Krebsarten, gegen die es bis heute keine Früherkennung gibt. Selbst wer regelmäßig zur gynäkologischen Vorsorge geht, kann ihn nicht rechtzeitig entdecken. Etwa 70 Prozent aller Fälle werden erst in einem späten Stadium diagnostiziert. Bis zu 25 Prozent dieser Fälle sind erblich bedingt, oft durch eine Mutation in den BRCA1- oder BRCA2-Genen, jenen Genen, die durch Angelina Jolie weltweit bekannt geworden sind. Wir sprechen darüber, wann ein Gentest sinnvoll ist, wer ihn bezahlt, warum auch die väterliche Familienseite zählt, und welche Möglichkeiten der Prävention es gibt. Eine bewegende Folge, ein Weckruf für jede Frau mit Krebsfällen in der Familie.  In dieser Folge sprechen wir u.a. über folgende Themen: Warum etwa 70 Prozent aller Eierstockkrebsfälle erst in einem späten Stadium entdeckt werden. Warum die regelmäßige gynäkologische Vorsorge bei Eierstockkrebs nicht ausreicht. Was die BRCA1- und BRCA2-Mutation für das Krebsrisiko bedeutet. Warum auch die väterliche Familienseite für das Vererbungsrisiko zählt. Warum 30 bis 50 Prozent der Frauen mit familiärer Belastung nie einen Gentest erhalten. Wann die Krankenkasse den Gentest bezahlt und welche Kriterien gelten. Wie Tumor-Risiko-Sprechstunden und Zentren für familiären Brust- und Eierstockkrebs helfen können. Wie Danielas Weg von ersten Symptomen über mehrere Fehldiagnosen bis zur Diagnose verlief. Warum BRCA1-Trägerinnen häufig gut auf eine Chemotherapie ansprechen. Was die neue Immuntherapie mit Immuncheckpoint-Inhibitor bei Eierstockkrebs leistet. Wie die vorbeugende Entfernung der Eierstöcke das Risiko fast auf null senken kann. Warum Angelina Jolie zur Symbolfigur für Frauen mit BRCA-Mutation wurde.  Weitere Informationen zu Prof. Dr. Marion Kiechle findest du hier: https://www.professoren.tum.de/kiechle-marion  Du interessierst dich für Gesunde Langlebigkeit (Longevity) und möchtest ein Leben lang gesund und fit bleiben, dann folge mir auch auf den sozialen Kanälen bei Instagram, TikTok, Facebook oder YouTube.  https://www.instagram.com/nina.ruge.official https://www.tiktok.com/@nina.ruge.official https://www.facebook.com/NinaRugeOffiziell https://www.youtube.com/channel/UCOe2d1hLARB60z2hg039l9g  Disclaimer: Ich bin keine Ärztin und meine Inhalte ersetzen keine medizinische Beratung. Bei gesundheitlichen Fragen wende dich bitte an deinen Arzt/deine Ärztin.  STY-290 

 In this episode of Fertility Forward, Rena and Dara are joined by journalist and mother, Stephanie Butnick, for an honest conversation about IVF, genetic testing, and the emotional complexities of building a family. Stephanie shares how her journey with RMA began after learning her husband carries a BRCA1 mutation, and why they chose to pursue IVF with pre-implantation genetic testing. She reflects on her second IVF experience and how it differed from the first, while also opening up about the incredible support she received throughout her care. Together, they discuss what it was like for her husband to navigate these experiences as the BRCA1 carrier and how they plan to one day talk to her daughters about the journey that brought them into the world. Stephanie also shares how speaking openly about her experience has helped her connect with others facing similar challenges, emphasizing the importance of community, transparency, and keeping sight of the bigger picture throughout the fertility journey. 

Most people think breast cancer treatment ends when the tumor is gone. Science says that's where the real damage often begins, and the woman making that argument was diagnosed at 28, lost her mother to ovarian cancer the same year, and turned her own dismissal by the medical system into a specialization that now treats women nobody else will touch. In this episode, I sit down with Dr. Corinne Menn Board Certified OBGYN, breast cancer survivor, and one of the few specialists in the world treating menopause in cancer survivors. We break down why 80% of women diagnosed with breast cancer have no strong family history, why tamoxifen and aromatase inhibitors quietly devastate brain, bone, and sexual health, and why telling a woman with severe vaginal atrophy to use coconut oil is not evidence-based medicine. Dr. Corinne also opens up about her own diagnosis, her premature menopause at 28, the truth about hormone replacement therapy after breast cancer, and the BRCA, ApoE4, and surgical menopause snowball nobody is putting together for patients. This conversation will completely change how you think about breast cancer, menopause, and the women's health crisis hiding in plain sight. Reduce your risk of Alzheimer's with my science-backed protocol for women 30+: https://go.neuroathletics.com.au/youtube-sales-page Subscribe to The Neuro Experience for evidence-based conversations at the intersection of brain science, longevity, and performance. _____ TOPICS DISCUSSED 00:00 Intro: Why Nobody Is Coming to Save Breast Cancer Survivors 01:05 Karin's Origin Story: Diagnosed at 28, Losing Her Mom, and Premature Menopause 03:06 The 85% Cure Rate Lie: Why Survival Comes at a Brutal Cost 06:13 Breast Cancer Is Not One Disease: Why 80% Have No Family History 08:14 BRCA1, BRCA2, and the Genetic Mutations Most Women Never Get Tested For 13:14 Karin's Own Genetic Test Story and Why 23andMe Is Not Enough 15:07 BRCA1 vs BRCA2: Age of Onset and When to Remove Ovaries 17:30 The Biology of Estrogen: Why Estrogen Does Not Cause Breast Cancer 23:40 Birth Control, Breastfeeding, and the Real Risk Factors 26:17 Alcohol, Inflammation, and the Toxins Driving Cancer Rates 27:46 Tamoxifen Explained: What It Does to Your Brain, Bones, and Body 34:23 Aromatase Inhibitors: Putting Your Estrogen in the Basement 37:15 Where Women Go When No Doctor Will Help Them 41:17 Oophorectomy, Early Menopause, and the 6 to 12% of Women Affected 44:26 Why Black Women Face the Highest Risk and the Least Care 46:20 The ApoE4, BRCA, and Surgical Menopause Snowball 48:02 Coconut Oil Is Not Medicine: The Vaginal Estrogen Truth 50:35 HRT Denial and the Myths Keeping Women From Treatment 51:13 Who Owns the Breast Cancer Survivor After Treatment Ends 54:18 Why the System Fails: Reimbursement, Resources, and Survivorship Gaps 01:00:07 Can You Be on Tamoxifen and Hormone Replacement Therapy? 01:03:26 Three Neurologists, One Tau Test, and the Dementia Dismissal 01:06:26 Positive Stories: Women Who Took Back Their Health and Won 01:09:16 The One Wish: Valuing Ovarian Function Beyond Reproduction _______ Thank you to our sponsors KetoneIQ: https://ketone.com/NEURO for 30% OFF DailyBasis: https://www.dailybasislife.com/NEURO for 50% off first month IQBARS: https://www.eatiqbar.com/ Biologica: https://biologica.com/NEURO Up to 32% off first subscription order Cure Hydration: https://www.curehydration.com/ Use code NEURO gets 20% off Honey Love: https://www.honeylove.com/NEURO Save 20% Off Honeylove #honeylovepod _______ I'm Louisa Nicola - clinical neurophysiologist - Alzheimer's prevention specialist - founder of Neuro Athletics. My mission is to translate cutting-edge neuroscience into actionable strategies for cognitive longevity, peak performance, and brain disease prevention. If you're committed to optimizing your brain- reducing Alzheimer's risk - and staying mentally sharp for life, you're in the right place. Stay sharp. Stay informed. Join thousands who subscribe to the Neuro Athletics Newsletter → https://bit.ly/3ewI5P0 Instagram: https://www.instagram.com/louisanicola_/ Twitter : https://twitter.com/louisanicola_ Learn more about your ad choices. Visit megaphone.fm/adchoices

Featuring an interview with Dr Wassim Abida, including the following topics: Comparing the clinical relevance of BRCA1 and BRCA2 mutations in prostate cancer (0:00) Relevance and interpretation of LOH (loss of heterozygosity) scores (4:37) Incidence and clinical relevance of PALB2 mutations; role of genetic counseling in the care of patients with prostate cancer (9:33) Key considerations surrounding toxicities associated with PARP inhibitors (15:25) Potential role of saruparib; evolving nomenclature in prostate cancer (22:36) Approach to newly diagnosed metastatic prostate cancer (26:16) Clinical relevance of PSMA-targeted PET imaging results (29:49) Case: A man in his mid 70s with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious BRCA alteration receives olaparib/abiraterone/prednisone upon relapse (32:15) Combining PARP inhibitors with other DNA repair inhibitors; insights on the PSMAddition trial (37:14) Case: A man in his mid 60s with metastatic prostate adenocarcinoma and a BRCA germline mutation receives niraparib/abiraterone/prednisone (43:17) Case: A man in his early 60s with mCRPC and CDK12 mutations receives talazoparib/enzalutamide (45:54) CME information and select publications

Dr. Dipali Sharma and her team published two papers that found links between bacteria, including F. nucleatum, the bacterium that causes periodontal disease, and the development of breast cancer. Listen to the episode to hear Dr. Sharma explain: her work to figure out how bacteria travel from the gut or mouth to the breast the changes the bacteria cause in breast cells why breast cells with BRCA1 mutations were more likely to have higher levels of bacteria in them how research to inhibit a specific enzyme may one day lead to a new breast cancer treatment

Lisa Beck, a fitness-focused director of operations from Keller, Texas, was so healthy she wasn't even nervous about her biopsy. The call telling her she had endometrial cancer stopped her in her tracks. What followed was two years of navigating conflicting diagnoses (serous vs. endometrioid cancer), doctors eager to remove everything they could, and her own fierce determination to slow down and make informed decisions. She sought opinions at Texas Oncology, MD Anderson, and Memorial Sloan Kettering, eventually discovered a BRCA1 mutation, and pursued integrative treatments in Tijuana alongside conventional care. Three years cancer-free, Lisa now leads a HealingStrong group in Keller and is newly addicted to pickleball.HealingStrong's mission is to educate, equip and empower our group leaders and group participants through their journey with cancer or other chronic illnesses, and know there is HOPE. We bring this hope through educational materials, webinars, guest speakers, conferences, community small group support and more.Please take advantage of our FREE resources below to help you along your health and healing journey:Support Group DirectoryHolistic Curriculum - Participant GuideSupport Our Mission - DonateAdditional Health ResourcesListen to Previous EpisodesWebsite: healingstrong.org

If you finished cancer treatment and then felt completely abandoned when it came to what happened to your body next...this episode is for you. Jen sits down with Dani Binnington, founder of the global non-profit Menopause and Cancer, host of the Menopause and Cancer podcast (212+ episodes), and author of Navigating Menopause After Cancer. Dani was diagnosed with triple negative breast cancer at 33...a young mom to three children under five — and later pushed into sudden surgical menopause after her oophorectomy as a BRCA1 carrier. No one counseled her. No one warned her. So she built the resource she wished had existed. This conversation covers everything nobody tells you...and everything you deserve to know. In this episode: Dani's diagnosis at 33 with triple negative breast cancer, her BRCA1 mutation, and the decision to have a double mastectomy and oophorectomy What makes cancer-induced menopause fundamentally different from natural menopause...and why it's a harder experience The difference between chemotherapy-induced, surgical, and medically-induced menopause...and what each means for your body Why 50% of women on endocrine therapy don't complete their full 5–10 year course because of menopausal side effects...and what to do if that's you The truth about vaginal estrogen for breast cancer survivors — why over 88% struggle with genitourinary symptoms and why this treatment is safer than most oncologists let on Jen's own story: years of fear around vaginal estrogen, the nearly-didn't-make-it-to-the-bathroom moment that finally changed her mind HRT after cancer — what the guidelines actually say, and how to have an informed conversation with your doctor The "beautiful platter" framework: Dani's approach to menopause management that includes lifestyle, medical options, complementary therapies, and everything in between Phytoestrogens, Mediterranean diet, exercise, acupuncture, SSRIs for hot flashes....the full evidence-based toolkit Simple tweaks that can make a huge difference if you're struggling on hormone-blocking medication right now How Menopause and Cancer started as a Facebook group and grew into a global community with 212 podcast episodes, in-person events, and an international book written with 20 doctors Why the burden of figuring all this out should NOT fall on patients alone...and what Dani is doing to change that Links & Resources Mentioned: Navigating Menopause After Cancer by Dani Binnington — https://a.co/d/0dxiGTR5 Menopause and Cancer podcast — Listen HERE Dani Binnington on Instagram — https://www.instagram.com/menopause_and_cancer/ Not Today Cancer Inner Circle — INFO HERE BrocElite - 20% off LINK You are not stuck. Your symptoms will fluctuate. And you have more options than anyone has probably told you. Not today, cancer. Medical Disclaimer: Nothing shared in this episode constitutes medical advice. Always consult your oncologist or healthcare provider before making any changes to your treatment plan.

Send us Fan MailI did something I've never done before for this episode — I went live from the middle of a national park. This is DigiPath Digest #42, broadcasting from the Great Sand Dunes National Park in Colorado via Starlink from my family road trip. Yes, it actually worked. And so did the papers.This episode covers four papers that all ask the same uncomfortable question from different angles: how close is AI to being genuinely useful in real pathology practice — and what's still standing in the way? From LLMs interpreting cervical Pap smears, to AI guiding breast cancer treatment decisions from a simple H&E slide, to a practical roadmap for bringing generative AI into oncology workflows — this one covers a lot of ground.I also introduced something new: my AI-powered paper summary podcast subscription. For $7 a month, AI hosts summarize digital pathology literature in a journal-club style so you can stay current without spending hours reading abstracts. I walk through how it works and why I built it.What we cover:[00:00] Going live from the wilderness — Starlink, sand dunes, and a very cold morning[02:01] How I use AI-generated audio summaries to prep for each DigiPath Digest[03:19] Paper 1: Can LLMs like ChatGPT and Gemini interpret cervical cytology? Spoiler: ~47–48% exact concordance — promising, but not there yet[10:23] Bonus: My new AI-powered paper summary subscription — $7/month, journal-club style[14:05] Paper 2: AI in oral oncology — CNNs for early lesion detection, multimodal prognostics, and the real barriers still blocking clinical adoption[20:28] Paper 3: Generative AI in oncology — from chat tools to agentic EHR-integrated assistants, and why augmentation is the goal, not automation[25:35] Paper 4: Computational pathology in breast cancer — predicting BRCA1/2, HER2, Oncotype DX, and treatment response from standard H&E slides[31:39] Final thought: the floor just got raised for all of us — how I think about new technology in pathologyResources & Links:Paper 1 – LLMs & Cervical Cytology (PubMed): https://pubmed.ncbi.nlm.nih.gov/41931983/Paper 2 – AI in Oral Oncology (PubMed): https://pubmed.ncbi.nlm.nih.gov/41930554/Paper 3 – Generative AI in Oncology Practice (PubMed): https://pubmed.ncbi.nlm.nih.gov/41930309/Paper 4 – AI & Digital Pathology in Breast Cancer (PubMed): https://pubmed.ncbi.nlm.nih.gov/41930306/Watch on YouTube: https://www.youtube.com/live/O2hOU4gM0Bk?si=oH8iJ8HiBb29USG3Digital Pathology Place: https://www.digitalpathologyplace.comSupport the showGet the "Digital Pathology 101" FREE E-book and join us!

Send us Fan MailPaper Discussed in this Episode: How artificial intelligence applied to digital pathology could guide treatment personalization in breast cancer. T. Ruelle, T. Grinda, L. Del Mastro, M. Lacroix-Triki, B. Pistilli & G. Gessain. ESMO Real World Data and Digital Oncology 2026.Episode Summary: In this journal club episode, we step into the reality of computational pathology and explore how artificial intelligence is fundamentally transforming breast cancer diagnostics. We examine a comprehensive review detailing how AI not only assists overburdened healthcare systems but also unlocks invisible genomic data straight from a standard $5 hematoxylin-eosin (H&E) glass slide. What happens when a machine can predict complex DNA mutations just by evaluating the structural architecture of cells?In This Episode, We Cover:• The Diagnostic Bottleneck: Understanding the critical worldwide shortage of pathologists colliding with a projected 3.2 million global breast cancer diagnoses by 2050, and why the system is under unprecedented strain.• The Biomarker Battle: Why the human visual cortex struggles to quantify faint immunohistochemistry stains, and how AI acts as a perfect "digital colorimeter". We discuss its near-perfect concordance in assessing crucial biomarkers like Ki-67, ER, PR, PD-L1, and the newly established HER2-low status.• Seeing the Invisible (Predictive AI): How deep learning transcends visual diagnostics to predict treatment outcomes, such as a patient's response to neoadjuvant chemotherapy. We also discuss AI's ability to infer Homologous Recombination Deficiency (HRD) and BRCA1/2 mutations by identifying macroscopic footprints like laminated fibrosis.• Decoding Genomic Assays: The potential to replace expensive, tissue-consuming genomic tests like Oncotype DX with AI models (such as Orpheus) that predict recurrence risk straight from digitized slides, achieving accuracy that rivals the tests themselves.• Roadblocks to Reality: The major clinical friction preventing global rollout. We discuss the steep infrastructure costs of whole-slide scanners, the danger of AI bias across diverse hospital datasets, and the ethical "black box" problem requiring the evolution of transparent, agent-based AI.Key Takeaway: Computational pathology is moving far beyond basic diagnostic assistance. By successfully reading the structural language of biology, AI proves it can extract costly, invisible molecular data from standard biopsies, fundamentally changing the economics and accessibility of global personalized healthcareSupport the showGet the "Digital Pathology 101" FREE E-book and join us!

What if the cancer treatments you trust are built on the wrong foundation?Dr. Thomas Seyfried has spent decades building the scientific case that cancer isn't a genetic disease. It's a metabolic one. And that distinction changes everything. He breaks down exactly why cancer cells can't survive without glucose and glutamine, why conventional oncology has largely ignored this, and why managing cancer without toxic side effects isn't just possible. It's already happening.Dr. Seyfried also explains why eating meat won't raise your glutamine levels the way most people fear, how nutritional ketosis can cut chemotherapy doses in half, and why a drug called DON could be a turning point in metabolic cancer care if the FDA ever gets out of the way. If you or someone you love is navigating a cancer diagnosis, this conversation could reshape how you think about treatment options. Don't wait to hear it.Ready to try fasting but don't want to do it alone? Join Dr. Katie's 3-Day Guided Fast, for expert support, daily live calls, and a community to fast alongside: Sign-Up  Download the FREE Healing Tools Guide: https://bit.ly/drkatie-giftguideMORE FROM KATIE DEMING M.D.6 Pillars of Healing Cancer Workshop Series - Click Here to EnrollTransform your hydration with the Spring Aqua System:  https://springaqua.info/drkatieFollow Dr. Katie Deming on Instagram: https://www.instagram.com/katiedemingmd/Please Support the ShowShare this episode with friends & familyGive a Review on SpotifyGive a Review on Apple PodcastWatch on YoutubeDISCLAIMER: The Born to Heal Podcast  is intended for informational purposes only and is not a substitute for seeking professional medical advice, di...

Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago.In this episode, OncLive On Air® partnered with Two Onc Docs to spotlight the most practice-informing data to come out of the 2026 Genitourinary Cancers Symposium.In prostate cancer, the phase 3 PEACE-3 trial (NCT02194842) demonstrated a clear overall survival (OS) benefit with the combination of radium-223 and enzalutamide (Xtandi) compared with enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC). The phase 2 BRCAAway trial (NCT03012321) showed that for patients with mCRPC with BRCA1/2 or ATM mutations, combination therapy with olaparib (Lynparza) and abiraterone led to a longer median progression-free survival (PFS) than sequential treatment. Additionally, the POSEIDON meta-analysis indicated that short-term hormone therapy is adequate for most patients with prostate cancer receiving postoperative radiotherapy, as longer durations did not improve OS.In bladder cancer, the phase 3 KEYNOTE-B15 trial (NCT04700124) showed that neoadjuvant enfortumab vedotin-ejfv (Padcev) combined with pembrolizumab (Keytruda) significantly improved OS and event-free survival vs neoadjuvant chemotherapy in cisplatin-eligible patients with muscle-invasive bladder cancer, despite notable toxicities like skin and ocular adverse effects. Furthermore, the phase 2 RC48G001 trial (NCT04879329) found that disitamab vedotin (RC48) generated responses in patients with metastatic urothelial carcinoma, including those with HER2-low expression.Regarding renal cell carcinoma (RCC), the phase 3 LITESPARK-011 trial (NCT04586231) showed a PFS benefit with belzutifan plus lenvatinib vs cabozantinib in the second-line setting. In the adjuvant setting, the phase 3 LITESPARK-022 study (NCT05239728) demonstrated that adding belzutifan (Welireg) to pembrolizumab improved disease-free survival vs placebo plus pembrolizumab in patients with resected clear cell RCC.Finally, regarding testicular cancer, a phase 2 trial (NCT04876456) of cabozantinib showed meaningful activity in patients with relapsed/refractory germ cell tumors. Drs Armstrong and Tawagi noted that this marks the first nonchemotherapy agent to demonstrate such clinical benefit in this population, providing a new option for patients who have exhausted traditional treatment regimens.

"I'm so concerned about that being a fracturing of our psyche, in which we only allow empowerment... Can we just have someone to stand with us in that space? So that the process, no matter what we choose, is a process of self connection." - Sarah Champie   On this episode of Transforming Trauma, host Emily Ruth welcomes Sarah Champie (LCSW), a licensed trauma therapist and NeuroAffective Relational Model® (NARM®) practitioner who specializes in supporting individuals and families navigating hereditary cancer, genetic testing, and preventative surgery decisions. Sarah is also the creator and host of the podcast Walking the Genetic Line.   Sarah draws on her own experience as a BRCA1 carrier and the childhood loss of her mother to ovarian cancer to illuminate what she calls the "portal moment" of receiving genetic testing results. Together, Emily Ruth and Sarah explore why empowerment-only narratives fall short, how NARM® survival styles shape our responses to medical urgency, and the critical gap in emotional care for those facing life-altering body decisions. Sarah makes a compelling case that healing in this space means holding agency and grief at the same time, honoring the complexity of identity shifts, projective memory, and the deep longing for connection that surfaces when mortality enters the room.   We invite you to listen to the full episode and follow Transforming Trauma on Apple Podcasts, Spotify, YouTube, or your favorite podcast app. *** SPACE: SPACE is an Inner Development Program of Support and Self-Discovery for Therapists on the Personal, Interpersonal, and Transpersonal Levels offered by the Complex Trauma Training Center. This experiential learning program offers an immersive group experience designed to cultivate space for self-care, community support, and deepening vitality in our professional role as therapists. Learn more about how to join. *** The Complex Trauma Training Center: https://complextraumatrainingcenter.com View upcoming trainings: https://complextraumatrainingcenter.com/schedule/ *** The Complex Trauma Training Center (CTTC) is a professional organization providing clinical training, education, consultation, and mentorship for psychotherapists and mental health professionals working with individuals and communities impacted by Adverse Childhood Experiences (ACEs) and Complex Trauma (C-PTSD). CTTC provides NARM® Therapist and NARM® Master Therapist Training programs, as well as ongoing monthly groups in support of those learning NARM. CTTC also offers the SPACE Inner Development Program for Therapists, providing a depth-oriented professional community for those seeking a supportive network of therapists focused on three levels of shared human experience: personal, interpersonal & transpersonal. The Transforming Trauma podcast embodies the spirit of CTTC – best described by its three keywords: depth, connection, and heart - and offers guidance to those interested in effective, transformational trauma-informed care.   *** We want to connect with you! Facebook  Instagram  LinkedIn YouTube X ( Twitter )    

Listen to this audio podcast covering biomarker testing in patients with prostate cancer. Learn from Sara Traverso, MMS, PA-C, and Brenda Martone, MSN, ANP-BC, AOCNP, about when to conduct germline and somatic genetic testing in patients with prostate cancer, discussing testing with patients and their caregivers, recognizing actionable biomarkers, and improving APP confidence in the application of biomarker testing results to practice. Presenters: Sara Traverso, MMS, PA-C  Physician Assistant Northwestern Medicine Robert H. Lurie Comprehensive Cancer Center Genitourinary Oncology Chicago, Illinois Brenda Martone, MSN, ANP-BC, AOCNP Nurse Practitioner Northwestern Medicine Chicago, Illinois Link to full program: https://bit.ly/3PB4ZJR Get access to all our new podcasts by subscribing to the Decera Clinical Education Oncology Podcast on Apple Podcasts, YouTube Music, or Spotify. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Listen to JCO OP's Art of Oncology Practice article, "When Cancer Becomes a Headline: Reflections from the Clinic" by Dr. Carlos Stecca. The article is followed by an interview with Stecca and host Dr. Mikkael Sekeres. Dr Stecca reflects on the impact of the public illness and death of Brazilian singer and actress Preta Gil on his patients with colorectal cancer and on his own practice as a medical oncologist. TRANSCRIPT Narrator: When Cancer Becomes a Headline: Reflections from the Clinic, by Carlos Stecca, MD Dr. Mikkael Sekeres: Welcome back to JCO's Cancer Stories: The Art of Oncology. This ASCO podcast features intimate narratives and perspectives from authors exploring their experiences in oncology. I'm your host, Mikkael Sekeres. I'm Professor of Medicine and Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center, University of Miami. What a pleasure it is today to have Dr. Carlos Stecca, a medical oncologist at Evangelical Mackenzie University Hospital, to discuss his JCO Oncology Practice article, "When Cancer Becomes a Headline: Reflections From the Clinic". Dr. Stecca and I have agreed to call each other by first names. Carlos, thank you for contributing to JCO Oncology Practice and for joining us today to discuss your article. Dr. Carlos Stecca: So great to be here. Thank you so much for having me. Dr. Mikkael Sekeres: I wonder if we could start off by asking you to tell us about yourself. Where are you from and what led you to this point in your career? Dr. Carlos Stecca: So I am Brazilian. I was born in Brazil in a small town in the south of Brazil, and I did my medical training all in Brazil. So I did medical school here, internal medicine, and medical oncology. My residency period ended in early 2018. I did my residency at the AC Camargo Cancer Center, which is in Sao Paulo. And then right after that, I moved closer to my parents to start my journey as a medical oncologist. And I stayed here in the south for two more years. And then I was lucky enough to be accepted for a clinical research fellowship in genitourinary malignancies at the Princess Margaret Cancer Center. And I had the pleasure to work with Dr. Kala Sridhar for two years. So this was during the pandemic, so 2020, 2021. And then right after that, I moved back to Brazil. And I've been here for the past four years working as a medical oncologist specialized in genitourinary malignancies. But also, well, unfortunately here in Brazil most of us cannot do only one site, so we have to do a little bit more, so I'm doing gynae and GI as well. And in a few days, I'm moving back to Canada. I was lucky enough again to be accepted for a position at the University of British Columbia, so I'm moving in a few days. Dr. Mikkael Sekeres: Oh, my word. We caught you just in time then. Dr. Carlos Stecca: Yeah, yeah. I'm moving in four days now. Dr. Mikkael Sekeres: I can't imagine what it's like to be going between those extremes of weather from Canada down to Brazil. Did your teeth crack when you did that? Dr. Carlos Stecca: Something like that. Yeah, it was like, I moved in December. So in December we have summer here in Brazil, and it was like 35, 40 degrees Celsius when I left Brazil at the airport. And when I arrived, it was close to minus 20 when I went to Toronto. Yeah. Dr. Mikkael Sekeres: Oh, my word. Dr. Carlos Stecca: It was rough. Dr. Mikkael Sekeres: Well, those of us who live at or near the Southern Hemisphere, I will tell you, I've started to wear puffy jackets and snow caps when it drops into the 60s. Good luck with reacclimating to Canada. I wonder if we could talk a little bit about the story that sparked this terrific essay. It was so interesting. The Brazilian singer and actress Preta Gil died of rectal cancer in July of 2025 at the age of 50. And she went public with her diagnosis. What is it that she communicated to the public about colorectal cancer? Dr. Carlos Stecca: So she was very open about her diagnosis since the beginning. So this was very interesting. She is very famous here. She had tons of followers on Instagram and social media, and she was very outspoken about her diagnosis since the first beginning. So she was diagnosed with an early stage disease, and she did a great job raising awareness for this condition, for colorectal cancer. She had a beautiful journey discussing the specifics of her case. Dr. Mikkael Sekeres: So she talked both about her diagnosis and some of the treatments she was undergoing, but also about symptoms of cancer, right? Dr. Carlos Stecca: She really engaged in this discussion about her diagnosis and how she found out about her cancer. So rectal bleeding, this was disclosed in her stories on Instagram, and so she was very open about this. And it really helped people understand the condition, and it really increased the number of screening tests that Brazilians were doing. And of course, we saw this increasing uptake of the screening tests, which was amazing. Dr. Mikkael Sekeres: In a way, I think she did a real public service, I think, both for early detection of colorectal cancer with symptoms, also for screening, so asymptomatic people who would undergo colonoscopies, and also demystified a little bit the treatment of colorectal cancer. In the US, we saw a similar phenomenon when the actor Chad Boseman of Black Panther movie franchise fame died of colorectal cancer in 2020 at the age of 43. These deaths have also sparked an international conversation about cancer in younger adults. Are you seeing that in your clinic? Dr. Carlos Stecca: Yes, definitely. We're seeing many more cases of cancer diagnosed in the younger population, right? So yeah, this discussion was very important to have, not only because the screening tests increased in patients after the age of 50 years old without any symptoms, but also raised awareness for those symptoms that should trigger the proper investigation. Dr. Mikkael Sekeres: I wonder if you could speculate a little bit about why it is that we're seeing more cancer in younger adults. Do you think it has anything to do, for example, with diet and people eating more ultra-processed foods? Is it a phenomenon? I've even heard people talk about microplastics and whether that could be contributing. Also, recently, there was an article that came out that speculated that while we're seeing more cancers in younger adults, we're not seeing more deaths in younger adults, so we may just be picking these up earlier as more people are going to be screened or for additional testing at a younger age. Dr. Carlos Stecca: Yeah, I think so. I think this is definitely the case. I think younger adults are eating more processed foods, and we know that this is an obvious risk factor for colorectal cancer and other cancers as well. And maybe obesity as well, we are seeing this as a pandemic now in the world, right? So we are seeing this especially in developing countries. And here in Brazil, of course, we are seeing this as a phenomenon. Dr. Mikkael Sekeres: It's so fascinating. I feel like we won't really know the answer about the uptick in cancers in younger adults for years until some of the data settle out, including the data about people during the COVID pandemic not going for screening and testing as often and whether we're now starting to see the downstream effects of that. Dr. Carlos Stecca: For sure, I think this is- well, during the pandemic I was in Canada, but shortly after the pandemic was coming to an end, I came back to Brazil, and I saw that. I saw that a lot of patients came to the clinic with more advanced cancers because they missed those opportunities of being seen by a physician during the pandemic, because of course, for obvious reasons, people were not coming to the clinic. And we saw that, a huge number of patients being diagnosed with late-stage disease because of that. Dr. Mikkael Sekeres: It's fascinating. There's a named phenomenon called the Angelina Jolie effect. I don't know if you remember following the actress's 2013 opinion piece about genetic testing for hereditary cancers such as BRCA1 and following her prophylactic mastectomy. She is a carrier of a mutation. There was a wave of testing that occurred thereafter. So some good can come from celebrities going public with their cancer diagnosis. Dr. Carlos Stecca: Oh, definitely, definitely. I think that more good can come from their diagnosis and them being verbal about this than the downsides. Of course, the positive side of it is definitely outweighing the negative effect. Dr. Mikkael Sekeres: You write a really thoughtful essay. You mention downsides, and there can be some downsides. One of the things you wrote in your essay was, "Yet for others already living with colorectal cancer, the same story had the opposite effect. Instead of empowerment, it fueled anxiety, guilt, and resignation. Some patients grew silent, fearing their treatment was futile as they compared themselves to a celebrity who had access to the best hospitals, specialists, and resources, and still passed away. Others questioned why they had not caught their cancer earlier, internalizing blame." Can you talk a little bit more about some of the unintended consequences of a celebrity who goes public with his or her cancer diagnosis? Dr. Carlos Stecca: That was exactly it, right? I was witnessing this in my clinic. I work in a public hospital here, and I would see those patients coming to me and voicing their concerns about their diagnosis, colorectal cancer, that was now in the spotlight because of that famous person that battled with colorectal cancer and unfortunately passed away after two years of starting her journey. And that was something quite difficult for the patients because, as you mentioned, and as I wrote in the text, some of those patients were in the public system and they were comparing themselves, comparing their diagnosis with the diagnosis of someone who had endless resources. And in fact, she even went to the United States and took part in a clinical trial. She participated in a clinical trial. And yet she was not able to overcome this diagnosis, and sadly she passed away. So, most of our patients were coming to the clinic and voicing their fears, like, "If even she couldn't get through this, how can I? I'm a simple person and I'm here in this world of limited resources." And here in Brazil, we do have the public system and the private system, and there is a huge gap between what we can do in one system and another. That was a concern that they voiced. Dr. Mikkael Sekeres: I'm sorry she passed away. How did you deal with that? So how did you respond to patients who said, "Gee, if this famous actress with unlimited resources dies from her cancer, what hope do I have?" Dr. Carlos Stecca: Yeah, so I think this is very difficult, right? And this is something that I was learning to understand now. Because as you mentioned, Chadwick Boseman and Angelina Jolie, we heard of those stories, but I never felt that this would be impactful in my clinic, that there would be patients voicing their concerns about their diagnosis being in the spotlight. And this is something that happened to me now. I would often see those patients, and I started to think about the downsides of a cancer being on a headline for those already living with cancer, and already living with that cancer and having their cancer in the spotlight. And so that was something that I needed to hear and address their concerns more actively than before, right? So this is something that is really important. And sometimes it is as important as discussing toxicity related to chemotherapy or other things related to the treatment itself. But addressing their concerns, it would be a way to alleviate the burden that the patients are experiencing from that. Dr. Mikkael Sekeres: So what would you say to them? If somebody said to you, "How can I do well when this famous actress didn't do well?", what would you say? Dr. Carlos Stecca: The first thing is to talk to the patient that every diagnosis is different. So we do have differences in staging, we do have differences in biology of the tumor. And as we study more those diseases and every type of cancer, but here, especially colorectal cancer, we are seeing that those differences are very important in the treatment and they will be part of the prognosis as well. So no disease is the same as other disease. So your experience is unique. So your diagnosis is in a certain way unique. Your treatment might be different, right? Dr. Mikkael Sekeres: I like how you personalized that for each patient. I really love how you end this essay. You write, "In those quiet moments after a headline, when fear enters the exam room, my responsibility is clear. I must not only prescribe treatment, but also restore perspective, dignity, and courage. Sometimes that is the most difficult, yet most essential part of being an oncologist." I remember, Carlos, one of my patients once described what we do as being almost pastoral. He himself was a minister and said this. And an important part of our job is to provide that context, but also a space where people can feel forgiveness for what they perceive as their fault. I wonder if you could reflect on that a little bit. How is it that, it almost sounds like it's too extreme, but we provide a sanctuary where patients can forgive themselves for the guilt they've been carrying around. Dr. Carlos Stecca: Yeah. No, I think this is very important. As medical oncologists, we are more than just physicians. We become friends with the patients, right? So most of the time I do create this relationship, this strong bond with the patient, because I worked as a family doctor before, so I treated patients very intimately as well. But nothing compares to being an oncologist now, because I think that the emotional burden associated with the profession is extremely high. And it's very difficult for the patient, for the family. And so we become part of their families and part of their story and their journey throughout their whole journey with the cancer. So it can be very emotional. I think that it's much more than being a physician and treating patients and prescribing treatments and discussing the biology of the tumor. And it's much more than that. And I think that being an oncologist entails all that, entails being part of their story and engaging in an emotional journey that they are having with the cancer. Especially here in Brazil, I think that the diagnosis of cancer has always been challenging. And I think that a patient's experience is unique and addressing the emotional part of it is very important. Dr. Mikkael Sekeres: Well, what a beautiful way to sum up what we do. We become part of our patients' stories and journey, and they become part of ours, and I think that's why we write about it. It has been such a pleasure to have Dr. Carlos Stecca to discuss his essay, "When Cancer Becomes a Headline: Reflections From the Clinic". Carlos, thank you so much for submitting your article and for joining us today. Dr. Carlos Stecca: Thank you so much for having me. It was a pleasure. If you enjoyed this episode, consider sharing it with a friend or colleague or leave us a review. Your feedback and support helps us continue to have these important conversations. If you are looking for more episodes and context, follow our show on Apple, Spotify, or wherever you listen and explore more from ASCO at asco.org/podcasts. Until next time, this has been Mikkael Sekeres for JCO's Cancer Stories: The Art of Oncology. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Show notes:Like, share and subscribe so you never miss an episode and leave a rating or review. Guest Bio: Dr Carlos Stecca is a medical oncologist at Evangelical Mackenzie University Hospital.

Approximately 5–10% of all breast cancers are hereditary, and among those, BRCA1 and BRCA2 mutations are responsible for about 60% of cases. Yet, overall, only about 1-2% of all breast cancers in the general population are caused by BRCA mutations. Once childbearing is complete, the NCCN recommends risk-reducing BSO in patients carrying these mutations. But what about the uterus? Since childbearing is complete, and the ovaries are now removed, the sole purpose of the uterus- which is to initiate, nourish, and grow a child -is no longer applicable. Is there a call for inclusion of a hysterectomy at time of risk reducing BSO? This has vast and important implications regarding subsequent hormone therapy. In this episode, which comes from one of our podcast family members, we will dive into the latest data pushing towards the inclusion of hysterectomy at time of prophylactic BSO. It's fascinating data from just last year (2025, in the Journal of the NCI). Listen in for details.1. Kotsopoulos J, Seca M, Gronwald J, et al. Menopausal Hormone Therapy and the Risk of Breast Cancer in Women With a Pathogenic Variant in BRCA1 or BRCA2. Journal of the National Cancer Institute. 2025. 2. Kotsopoulos J, Gronwald J, Karlan BY, et al. Hormone Replacement Therapy After Oophorectomy and Breast Cancer Risk Among BRCA1 Mutation Carriers. JAMA Oncology. 2018

Dr. Monty Pal and Dr. Atul Batra discuss the PLANeT study from India, which evaluated low-dose pembrolizumab in addition to neoadjuvant chemotherapy for triple-negative breast cancer, and its place among a growing body of international research on improving efficacy while reducing costs and toxicity with lower doses of immunotherapy. TRANSCRIPT Dr. Monty Pal: Hello and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist, professor, and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center, Los Angeles. My guest today, I think, is going to be a really riveting one. It's Dr. Atul Batra, who is an additional professor of medical oncology at the All India Institute of Medical Sciences, or AIIMS, in New Delhi. And he's also the senior author of the PLANeT study. It's a very compelling study that evaluated low-dose pembrolizumab in addition to neoadjuvant chemotherapy for triple-negative breast cancer. And it's really a big part of a growing body of research that's showing balanced efficacy when we use lower doses of immunotherapy instead of standard doses to reduce cost, as well as potentially toxicity. I think this has huge implications for our global audience, and I'm so thrilled to have you on the podcast today, Dr. Atul Batra, welcome. Dr. Atul Batra: Thank you, Dr. Pal. Dr. Monty Pal: And we'll just take it with first names from here since we're both friends. I have to give the audience some context. Atul, I had the great honor of visiting AIIMS New Delhi. For those that don't know, this is really, you know, the Harvard Medical School of India. It's the most competitive institution for medical training. And on the back end of that, there's also incredible resources when it comes to clinical trials and infrastructure. I just wanted to have you give the audience sort of a scope of the types of trials that you've been able to do at AIIMS New Delhi. Dr. Atul Batra: Thank you, Monty. So, I work at the All India Institute of Medical Sciences, and we had the honor and pleasure of having Monty here this month. And people are still in awe of his lectures that he delivered there. Coming back to our institute, so it's kind of a medical college. It's one of the oldest ones, it was built in 1956. We are lucky enough that we get the best of the residents and fellows because they have to go through an exam, a competitive exam, and mostly it's them who come to us and we're able to do some good work out here. Regarding the trials that we have conducted, we do conduct some investigator-initiated studies, and we try to answer the questions where we can help our own patients. Like, for example, this PLANeT study. Every other patient in the clinic was almost not able to afford Keytruda at the full dose, pembrolizumab, and we had a lot of evidence creeping in that a lower dose might be helpful. And that's how we planned this study. Before that, there are certain cancers that are peculiar to India, like gallbladder cancer, head and neck cancers. These are much more common in India as compared to the U.S., and there are some good studies that have been conducted from our own institute by our senior colleagues which have been presented at ASCO and published in the JCO. We also did the capecitabine hand-foot syndrome study that was known as the D-ToRCH study: 1% diclofenac gel that became the standard of care to prevent hand-foot syndrome.  So, that's kind of a brief overview of investigator-initiated studies. India is slowly and steadily becoming a partner of the global registration trials. And it's more recently, the last five years or so, we have seen that the number of phase 2 and phase 3 trials are increasing and we are able to offer now these trials as well to our patients. Dr. Monty Pal: That was a terrific overview. I just want to highlight for the audience, as we go through some of your discussions today around specific trials, the speed at which this can be done. Just for context, for me to accrue a clinical trial of 30 patients – I think many people have probably come across some of the work that I've done in the microbiome space – at a single institution, 30 patients, right, takes me about a year and a half, two years. We're going to go through some trials today where Dr. Batra and his team have actually, in fact, accrued close to 200 patients over a span of just a year, which is just remarkable by, I would say, any American standard. So, I see a real need for partnership and Atul, I'll kind of get back to that at the end. But without further ado, the focus of this podcast today, I think, is really this terrific presentation you gave in an oral session at ESMO and subsequently published in Annals of Oncology related to the PLANeT study. Would you give the listeners some context around what the study entailed and population and so forth? Dr. Atul Batra: So, we know the KEYNOTE-522 became the standard of care for triple-negative breast cancer, where Keytruda, when added at 200 mg, the standard dose every three weeks with neoadjuvant, increases the pCR from around 51% to 64% by a magnitude of around 13%. However, in India and other low-middle income countries, less than 5% of the patients actually have access to this dose of pembrolizumab. So, our standard of care was actually just chemotherapy till now. And this kind of led us to design this trial. There are data that come from previous trials conducted in India, from the Tata Memorial, done in head and neck space, some other studies done in Hodgkin's lymphoma, that a much lower dose, probably around one-tenth of the dose, works well in these cancers. So, that's where we designed the PLANeT study, where we gave the standard neoadjuvant chemotherapy in the control arm, and in the experimental arm we added 50 mg of pembrolizumab. This was given every six weeks for three doses. So, that's a total of 150 mg over the neoadjuvant period as compared to 1,600 mg that was given in the KEYNOTE-522 study. So, this was almost one-tenth of the study. Dr. Monty Pal: So, a tenth of the dose, which is just remarkable. I mean, that's just such an interesting concept. Dr. Atul Batra: And the results, when we – the primary outcome, this was a phase 2 study. We just wanted to see, is there a signal of activity? And to even our surprise, when we looked at the pathological complete response rates, in the control arm this was 40.5%, and in the experimental arm this was 53.8%. So, a difference came to around 13.3%; it was numerically, I mean, so much similar to what KEYNOTE-522 had with just these many doses. So, this was around 160 patients randomized over one year. We could randomize them in one year because of the load that we see. And the primary endpoint was met, and we could see that the path complete response did show a remarkable increase. We are still following these patients to see whether there is a difference in event-free survival at a longer follow-up. Until now, it's a small follow-up, so the number of events absolute, are different: four events in the experimental arm and 11 events in the control arm. So, we are seeing some signal even in this much short follow-up period as well. But we need to see more of what happens in the longer term. Dr. Monty Pal: That's so impressive. I wonder, with this lower dose, do you attenuate toxicity at all as far as you can gather? Dr. Atul Batra: So, although we shouldn't be doing kind of cross-trial comparisons, but if you look at thyroid dysfunction, we saw that around 10% of our patients had this thyroid dysfunction. This was compared to 15% in the KEYNOTE-522, that was a larger sample size though. But we're seeing that all the toxicities are somewhat less as compared to those in the standard dose. So, the exposure is less, but I mean, I can't really commit definitely on this. For this we would need much more data to say this with more confidence. Dr. Monty Pal: Yeah. I'm going to ask you a really tough question to follow up, and this is probably something that's on everyone's mind after reading a study like this. Is this something that is disease-specific that needs to be replicated across other histologies? The reason I ask this is, you know, you think about paradigms like, for instance, in the States we're toying between intravenous versus subcutaneous delivery of checkpoint inhibitors, and we have studies focused in specific histologies that might justify use across all histologies. With this particular phenomenon, do you think we need to do dedicated studies in renal cell or in colon cancer and other places where, you know, in selected settings we might use checkpoint inhibitors and then decide whether or not there's this dose equivalence, if you will? Dr. Atul Batra: That's a real tough one, though. But I'm happy to share that there are several ongoing studies within India currently. At our institute, my colleagues are leading studies in lung cancer space, cervical cancer. There was already a publication from Tata Memorial Hospital in head and neck cancers and we see that the signal has been consistent throughout. Regarding renal cancer, there was one study that was presented for sure at ASCO from CMC Vellore, that's again a center in South India. That was in RCC at a much lower dose. And for patients who cannot take the full dose, we actually are offering lower dose nivolumab in such patients and we are seeing responses. I mean, we haven't done those randomized trials again because the numbers are much lower in kidney cancers, we know. We could do this trial in triple-negative ones because we had support and we had numbers to conduct this trial. But I'm sure this should be a class effect. I mean, when we can get tumor-agnostic approvals, then some real-world data has come up in almost all tumors, we have seen that consistent effect across tumors. And as we speak of today, I'm also delighted to share that in India, yesterday, we had the first biosimilar of nivolumab and that's now available at a much, much lower price than the original patent product. There was a long ongoing lawsuit that was there, that's over now, and from yesterday onwards, I'm so happy to share here that we would have the first biosimilar of nivolumab that's available. That's going to bring the cost to almost like one-tenth already. Dr. Monty Pal: Wow. That's huge.  I'm going to be very selfish here for a second and focus on a study that is in the renal cell space that your group has done. You know, when it came out, I was really sort of intrigued by this study as well and it reflects sort of a different capability, I think, of AIIMS New Delhi, and that's in the, what I'm going to call, biomarker space. This, for the audience, was a prospective effort to characterize germline variants in patients with advanced kidney cancer. And it's something that we talk about a lot in the kidney cancer literature, whether or not we're missing a lot of these so-called hereditary patterns of RCC. Can you tell us a little bit about that study too? Dr. Atul Batra: Yeah, so that was led by one of our fellows, Chitrakshi Nagpal, and she's just completed her fellowship. And two years back we published that. So, that was done in almost 160 consecutive patients that we recruited over the span of just one year and we saw, apart from the common known mutations in RCC, that was around 5% or so, but a lot of other mutations were also seen that we don't generally see in kidney cancers and we see in other cancers like BRCA1, BRCA2 and others. We are still, I mean, doing those analyses to see whether we get more things out of there in the somatic: is there a loss of heterozygosity or was it just present and in there? Dr. Monty Pal: I thought it was a terrific study and again, I was just so blown away at the pace. I mean, as I look at 140 patients accrued over a span of one year, this is something that would take us perhaps three times as long at City of Hope, and that's with a very sort of, what I consider to be large and dedicated kidney cancer program. So, it really underscores, I think, the need for collaboration. And ever since I came back from my visit to you at AIIMS Delhi, I think I've just been sort of transformed in the sense of trying to think of better ways for us to collaborate. One tangible thing that I'm going to get cracking on is seeing whether or not perhaps we can form some partnerships through SWOG or what we call the NCTN, the National Clinical Trials Network here within the U.S. Talk to me about collaboration. I mean, you've been really terrific at this. How do you sort of envision collaboration enhancing the global landscape of oncology? Dr. Atul Batra: That's really amazing, Monty. That's what we need. We have the infrastructure, we have the manpower, we have patients. I mean, these are all high-volume centers. Unfortunately, we are a little less in numbers, so we are more clinically occupied as well. So, sometimes it's kind of tougher, but again, when it comes to helping out the patients, global collaboration, we need to kind of take you guys along with us and have our patients finish trials earlier. This is a win-win situation for patients, one, because they also get exposure or an option to participate in the clinical trials, and second, we can answer all these scientific questions that we have at a much faster pace. All those things can be done within a much shorter span of time for sure. We are so happy to hear that, and with open hands we are ready to collaborate for all these efforts. Dr. Monty Pal: That's awesome. You know, I came back thinking, gosh, this would be so ideal for some of these rare subtypes of kidney cancer. Prospective clinical trials that I'm running in that space where really we're threatened with closure all the time. And if we just sort of extended a hand to, you know, our partners in India and other countries, you know, I'm sure we could get this research done in a meaningful way and that's got to be a win for patients. Atul, I had such a terrific time chatting with you today. I'm looking forward to seeing lots more productivity from your group there. By the way, for our viewership here, take a look and see what AIIMS New Delhi is doing under the leadership of Dr. Batra and others. It is just a real powerhouse and I think that after doing so, you'll be enticed to collaborate as well.  I'm hoping this is the first of many times that we have you on the podcast. Thank you so much for joining. Dr. Atul Batra: Thank you so much for having me here, Monty. It was a pleasure as always speaking to you. And thank you again. Dr. Monty Pal: You got it.  Well, and thanks to our listeners. I encourage you to check out Dr. Batra's paper. We'll actually have a link to the study in the transcript of this episode.  Finally, if you value the insights that you heard today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:     Dr. Monty Pal   @montypal Dr. Atul Batra @batraatulonc Follow ASCO on social media:          ASCO on X    ASCO on Bluesky         ASCO on Facebook          ASCO on LinkedIn          Disclosures:       Dr. Monty Pal:      Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview     Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical     Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis     Dr. Atul Batra: Stock and Other Ownership Interests: Zydus Pharmaceuticals, Glenmark, Caplin Point Laboratories, Laurus Research Funding: AstraZeneca, Astellas Pharma, Alkem Laboratories

Have you ever felt like you were "waiting for the inevitable" because of your family history? In today's episode, Dr. Jen dives deep into the complex world of preventative mastectomies and elective hysterectomies. While conventional medicine often views these procedures as the only solution for high-risk genetic markers like BRCA1 and BRCA2, Dr. Jen explores the vital "middle ground." We discusses the limitations of standard screenings, the energetic significance of our feminine centers, and how epigenetics—the way we live, eat, and supplement—can influence how our genes actually express themselves. This isn't just about surgery; it's about understanding the "Root Cause" of why our bodies create dense tissue or fibroids in the first place. Themes: Understanding that while we may carry certain genes, our environment and hormonal balance (especially the role of progesterone) act as the "software" that runs the system. Why traditional mammography isn't a one-size-fits-all solution for dense tissue and the benefits of radiation-free options like thermography. Honoring the energetic "portals" of the breasts and womb, and how to maintain that feminine vitality even if physical organs are removed. Why hormonal replacement is a non-negotiable for long-term bone, brain, and heart health following a hysterectomy. Utilizing peptides and targeted lifestyle shifts to address inflammation and tissue health before a crisis occurs. Connect with Jen: 

This week we meet Maggie who shares her inspiring journey of resilience and personal growth, discussing her experiences with health challenges as a BRCA1 carrier and her career in special education. Maggie shares how her lack of knowledge and moments of isolation she felt during her double mastectomy revealed a major gap in society, leading her to create an online community dedicated to supporting other women experiencing something similar. Check out Maggie's tik tok here :) @mjwicki

Dr. Hope Rugo and Dr. Vivek Subbiah discuss innovative trial designs to enable robust studies for smaller patient populations, as well as the promise of precision medicine, novel therapeutic approaches, and global partnerships to advance rare cancer research and improve patient outcomes. TRANSCRIPT  Dr. Hope Rugo: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center [in Los Angeles]. The field of rare cancer research is rapidly transforming thanks to progress in clinical trials and treatment strategies, as well as improvements in precision medicine and next-generation sequencing that enable biomarker identification. According to the National Cancer Institute, rare cancers occur in fewer than 150 cases per million each year, but collectively, they represent a significant portion of all cancer diagnoses. And we struggle with the appropriate treatment for these rare cancers in clinical practice. Today, I am delighted to be joined by Dr. Vivek Subbiah, a medical oncologist and the chief of early-phase drug development at the Sarah Cannon Research Institute in Nashville, Tennessee. Dr. Subbiah is the lead author of a paper in the ASCO Educational Book titled "Designing Clinical Trials for Patients with Rare Cancers: Connecting the Zebras," a great title for this topic. He will be telling us about innovative trial designs to enable robust studies for small patient populations, the promise of precision medicine, and novel therapeutic approaches to improve outcomes, and how we can leverage AI now to enroll more patients with rare cancers in clinical trials. Our full disclosures are available in the transcript of this episode.  Dr. Subbiah, it is great to have you on the podcast today. Thanks so much for being here. Dr. Vivek Subbiah: Thank you so much, Dr. Rugo, and it is an honor and pleasure being here. And thank you for doing this podcast for rare cancers. Dr. Hope Rugo: Absolutely. We are excited to talk to you. And congratulations on this fantastic paper. It is such a great resource for our community to better understand what is new in the field of rare cancer research. Of course, rare cancers are complex and multifaceted diseases. And this is a huge challenge for clinical oncologists. You know, our clinics, of course, cannot be designed as we are being very uni-cancer focused to just be for one cancer that is very rare. So, oncologists have to be a jack of all trades in this area. Your paper notes that there are approximately 200 distinct types of rare and ultra-rare cancers. And, by definition, all pediatric cancers are rare cancers. Of course, clinical trials are essential for developing new treatment strategies and improving patient outcomes, and in your paper, you highlight some unique challenges in conducting trials in this rare cancer space. Can you tell us about the challenges and how really innovative trial designs, I think a key issue, are being tailored to the specific needs of patients with rare cancer and, importantly, for these trials? Dr. Vivek Subbiah: Rare cancers present a perfect storm of challenges. First, the patient populations are very small, which makes it really hard to recruit enough participants for traditional type trials. Second, these patients are often geographically dispersed across multiple cities, across multiple states, across multiple countries, across multiple zip codes. So, logistics become complicated. Third, there is often limited awareness among clinicians, which delays referrals and diagnosis. Add to that regulatory hurdles, funding constraints, and you can see why rare cancer trials are so tough to execute. To overcome these barriers, we are seeing some really creative novel trial designs. And there are four different types of trial designs that are helping with enrolling patients with rare cancers. The first one is the basket trial. So let us talk about what basket studies are. Basket studies group patients based on shared genetic biomarkers or shared genetic mutations rather than tumor type. So instead of running separate 20 to 30 to 40 trials, you can study one therapy across multiple cancers. The second type of trial is the umbrella trial. The umbrella trials flip that concept of basket studies. They focus on one cancer type but test multiple targeted therapies within it. The third category of innovative trials are the platform studies. Platform trials are another exciting innovation. They allow new treatment arms to be added or removed as the data matures and as the data evolves, making trials more adaptive and efficient. The final category are decentralized tools in traditional trials, which are helping patients participate closer to where they are so that they can sleep in their own bed, which is, I think, a game changer for accessibility.  These designs maximize efficiency and feasibility for rare cancer research and rare cancer clinical trials. Dr. Hope Rugo: I love the idea of the platform trials that are decentralized. And I know that there is a trial being worked on with ARPA-H (Advanced Research Projects Agency for Health) funding in triple-negative breast cancer as well as in lung cancer, I think, and others with this idea of a platform trial. But it is challenged, I think, by precision medicine and next-generation sequencing where some patients do not have targetable markers, or there isn't a drug to target the marker. I think those are almost the same thing. We have really seen that these precision medicine ideas and NGS have moved the needle in helping to identify genetic alterations. This helps us to be more personalized. It actually helps with platform studies to customize trial enrollment. And we hope that this will result in better outcomes. It also allows us, I think, to study drugs even in the early stage setting more effectively. How can these advances be best applied to the future of rare cancers, as well as the challenges of not finding a marker or not having a drug? Dr. Vivek Subbiah: Thank you so much for that question. I think precision medicine and next-gen sequencing, or NGS, are truly the backbone of modern precision oncology. They have transformed how we think about cancer treatment. Instead of treating based on where the tumor originated or where the tumor started, we now look at the genetic blueprint of cancer. The NGS or next-gen sequencing allows us to sequence millions of DNA fragments quickly. Twenty, 30 years ago, they said we cannot sequence a human genome. Then it took almost a decade to sequence the first human genome. Right now, we have academic centers and commercial sequencing companies that are really democratizing NGS across all sites, not just in academic centers, across all the community sites, so that NGS is now accessible. This means that we can identify these actionable alterations like picking needles in haystacks, like NTRK fusions, RET fusions, or BRAF V600E alterations, high tumor mutational burden. This might occur across not one tumor type, across several different tumor types. So for rare cancers, this is critical because some of these mutations often define the best treatment option. Here is why this matters. Personalized therapy, right? Instead of a one-size-fits-all approach, we can tailor treatment to the patient's unique molecular profile. For trial enrollment, this can definitely help because patients can join biomarker-driven trials even if their cancer type is rare or ultra-rare. NGS technology has also helped us in designing rational studies. Many times monotherapy does not work in these cancers. So we are thinking about rational combination strategies. So NGS technology is helping us. Looking ahead, I see NGS becoming routine in clinical practice, not just at major niche academic centers, but everywhere. We will see more tumor-agnostic approvals, more molecular tumor boards guiding treatment decisions in real time. And I think we are seeing an expanded biomarker setup. Previously, we used to have only a few drugs and a handful of mutations. Now with homologous recombination defects, BRCA1/2 mutation, and expanding the HRD and also immunohistochemistry, we are expanding the biomarker portfolio. So again, I personally believe that the future is precision. What I mean by precision is delivering the right drug to the right patient at the right time. And for rare cancers, this isn't just progress. It is survival. And it is maybe the only way that they can have access to these cutting-edge precision medicines. Dr. Hope Rugo: That is so important. You mentioned an important area we will get to in a moment, the tumor-agnostic therapies. But as part of talking about that, do you think that the trials should also include just standard therapies? You know, who do you give an ADC to and when with these rare cancers? Because some of them do not have biomarkers to target and it is so disappointing for patients and providers where you are trying to screen a patient for a trial or a platform trial where you have one arm with this mutation, one arm with that, and they do not qualify because they only have a p53 loss, you know? They just do not have the marker that helps them. But we see this in breast cancer all the time. And it is tough because we don't have good information on the sequencing. So I wonder, you know, just because for some of these rare cancers it is not even clear what to use when with standard treatments. And then that kind of gets into this idea of the tumor-agnostic therapies that you mentioned. There are a lot of new treatments that are being evaluated. We have seen approval of some treatments in the last few years that are tumor-agnostic and based on a biomarker. Is that the best approach as we go forward for rare cancers? And what new treatment options are most exciting to you right now? Dr. Vivek Subbiah: Tumor-agnostic therapies, really close to my heart, are real breakthrough therapies and represent a major paradigm shift in oncology. Traditionally, for the broad listeners here, we are used to thinking about designing clinical trials and therapy like where the cancer originated, breast cancer, kidney cancer, prostate cancer, lung cancer. A tumor-agnostic therapy flips that model. Instead of focusing on the organ, they target the specific genetic alteration or biomarker that drives cancer growth regardless of where the tumor started, regardless of the location of the tumor, regardless of the zip code of the tumor. So why is this so important for rare cancers? Because many rare cancers share molecular features with more common cancers. For instance, NTRK fusion might occur in pediatric sarcoma, a salivary gland tumor, or a thyroid cancer. Historically, each of these would require separate trials, which is nearly impossible, unfeasible to conduct in these ultra-rare cancers like salivary gland cancer or pediatric sarcomas. Tumor-agnostic therapies allow us to treat all those cancers with the same targeted drug if they share that biomarker. Again, we are in 2025. The first tissue-agnostic approval, the historic precedent, was in fact an immunotherapy. Pembrolizumab was approved in 2017, May 2017, as the first immunotherapy to be approved in a tumor-agnostic way for a genomic biomarker, for MSI-High and dMMR cancers. Then came the NTRK inhibitors. So today we have not one, not two, but three different NTRK inhibitors: larotrectinib, entrectinib, and repotrectinib, which show response rates of nearly more than 60 to 75% across a handful of dozens and dozens of cancer types. Then, of course, we have RET inhibitors like selpercatinib, which is approved tissue-agnostic, and pralsetinib, which also shows tissue-agnostic activity across multiple cancers. And more recently, combination therapy with a BRAF and MEK combination, dabrafenib and trametinib, received tumor-agnostic approval for all BRAF V600E tumors with the exception of colorectal cancer. And even recently, you mentioned about antibody drug conjugates. Again, I think we live in an era of antibody drug conjugates. And Enhertu, trastuzumab deruxtecan, which was used first in breast cancer, now it is approved in a histology-agnostic manner for all HER2-positive tumors defined by immunohistochemistry 3+. So again, beyond NGS, now immunohistochemistry for HER2 is also becoming a biomarker. So again, for the broad listeners here, in addition to comprehensive NGS that may allow patients to find treatment options for these rare cancers for NTRK, RET, and BRAF, immunohistochemistry for HER2 positivity is also emerging as a biomarker given that we have a new FDA approval for this. So I would say personally that these therapies are game changers because they open doors for patients who previously had no options. Instead of waiting for years for a trial in their specific cancer type, they can access a treatment based on their molecular profile. I think it is precision medicine at its finest and best. Looking ahead, the third question you asked me is what is exciting going on? I think we will see more of these approvals. My hope is that today, I think we have nine to ten approvals. My hope is that within the next 25 to 50 years, we will have at least 50 to 100 drugs approved in this space based on a biomarker, not based on a location of the tumor type. Drug targeting rare alterations like FGFR2 fusions, FGFR amplifications, ALK fusions, and even complex signatures like high tumor mutational burden. I think we will be seeing hopefully more and more drugs approved. And as sequencing becomes routine, we will identify more patients for these therapies. I think for rare cancers, this is not just innovative approach. This is essential for them to access these novel precision medicines. Dr. Hope Rugo: Yeah, that is such a good point. I do think it is critical. Interestingly in breast cancer, it hasn't been, you know, there is always like two patients in these tumor-agnostic trials, or if that. You know, I think I have seen one NTRK fusion ever. I think that highlights the importance for rare cancers. And you know, I am hoping that that will translate into some new directions for some of our rarer and impossible-to-treat subtypes of breast cancer. It is this kind of research that is really going to make a difference. But what about those people who do not have biomarkers? What if you do not fit into that? Do you think there is a possibility of trying to do treatments for rare cancers in some prospective way that would help with that? You know, it is really a huge challenge. Dr. Vivek Subbiah: Absolutely. I think, you know, you're right, usually many of these rare cancers are driven by specific biomarkers. And again, some of the pediatric salivary gland tumors or pediatric sarcomas like fibrosarcomas, they are pathognomonic with NTRK fusions. And again, given that we have a tumor-agnostic approval, now these patients have access to these therapies. And I do not think that we would have had a trial just for pediatric fibrosarcomas with NTRK fusions. So that is one way. Another way is SWOG, right? The SWOG DART [1609] had this combination dual checkpoint, it was called the DART study dual combination chemotherapy with ipi/nivo. Now here the rare cancer subtype itself becomes a biomarker and they showed activity across multiple rare cancer subtypes. They didn't require a biomarker. As long as it was a rare or ultra-rare cancer, these patients were enrolled into the SWOG DART trial and multiple arms have read out. Angiosarcoma, Kaposi sarcoma, even gestational trophoblastic disease. Again, they have shown responses in these ultra-rare, rare cancers. Sometimes they might be seeing one or two cases a whole year. And I think this SWOG effort, this cooperative group effort, really highlighted the need for such studies without biomarkers as well. Dr. Hope Rugo: That is such a fantastic example of how to try and treat patients in a collaborative way. And in the paper, you also emphasize the need for collaborative research efforts, you know, uniting resource expertise across different ways of doing research. So cooperative groups, advocacy organizations that can really help advance rare cancer research, improve access to new therapies, and I think importantly influence policy changes. I think this already happened with the agnostic approvals. Could you tell us more about that? How can we move forward with this most effectively? Dr. Vivek Subbiah: Personally, I believe that collaboration is absolutely critical and essential for rare cancer research. No single institution, no single individual, or no single state or entity can tackle these challenges alone. The patient populations are small and dispersed. So pooling resources is the only way to run these meaningful trials. Again, it is not like singing, it is like putting a huge, huge, I would say, an opera piece together. It is not a solo, vocal therapy, but rather putting a huge opera piece like Turandot. You know, you mentioned cooperative groups. Cooperative groups, as I mentioned earlier, the SWOG DART program, the ASCO [TAPUR study]. ASCO is doing a phenomenal work of the TAPUR study. Again, this ASCO TAPUR program has enrolled so many patients with rare cancers who otherwise would not have treatment options. NCI-MATCH, the global effort, right? NCI-MATCH and the ComboMATCH are great examples. They bring together hundreds of sites, thousands of clinicians to run large-scale trials that would be impossible for any individual center or institution. These trials have already changed practice. For instance, the DART demonstrated the power of immunotherapy in rare cancers and influenced NCCN guidelines. One of the arms of the NCI-MATCH study from the BRAF V600E arm contributed towards the BRAF V600E tissue-agnostic approval. So, the BRAF V600E tissue-agnostic approval was by a pooled analysis of several studies. The ROAR study, the Rare Oncology Agnostic Research study, the NCI-MATCH dataset of tumor-agnostic cohort, and another pediatric trial, and also evidence from literature and evidence of case reports. And all this pooled analysis contributed to the tissue-agnostic approval of BRAF V600E across multiple rare cancers. There are several patient advocacy organizations which are the real unsung heroes here. Groups like, for instance, we mentioned in the paper, Target Cancer Foundation, don't just raise awareness for rare cancer research, they actively connect patients to trials providing financial, emotional support, and even run their own studies like the TRACK trial. They also influence policy to make access easier. On a global scale, initiatives like DRUP in the Netherlands, the ROME study in Italy, the PCM4EU in Europe are expanding precision medicine across these borders. These collaborations accelerate research, improve trial enrollment, and ensure patients everywhere can have access to these cutting-edge therapies. Again, it is truly a team effort, right? It is a multi-stakeholder approach. Researchers, clinicians, investigators, industry, regulators, academia, patients, patient advocates, and their caregivers all working together. And it takes a village. Dr. Hope Rugo: Absolutely. I mean, what a nice response to that. And I think really exciting and it is great to see your passion about this as well. But it helps all of us, I think, getting discouraged in treating these cancers to understand what is happening moving forward. And I think it is also a fabulous opportunity for our junior colleagues as they rise up in academics to be involved in these international collaborative efforts which are further expanding. One of the things that comes up for clinical trials for patients, and I think it is highlighted with rare cancers because, as you mentioned, people are all over the place, you know, they are so rare. They are all far away. Our patients are always saying to us, "Should I go here for a phase 1 trial?" Can you talk a little bit about how we can overcome these financial and geographic burdens for the patients? You talked about having trials locally, but it is a big financial and just social burden for patients. Dr. Vivek Subbiah: Great point. Financial cost is a major barrier in rare cancer clinical trials. It is a major barrier not just in rare cancer clinical trials, but in clinical trials in general. The economics of rare cancer research are one of the toughest challenges we face. Developing a new drug is already expensive, often billions of dollars. On an average, it takes 2 billion dollars or 2.8 billion dollars according to some data from drug discovery to approval. For rare cancers, the market is tiny, which means the pharmaceutical companies have really little financial incentive to invest. That is why initiatives like the Orphan Drug Act were created to provide tax credits, grants, and market exclusivity to encourage development for rare diseases. Clinical trials themselves are expensive because the small patient populations mean longer recruitment times and higher per-patient costs. Geographic dispersion, as you mentioned, for the patients adds travel, coordination. That is why we need to think out of the box about decentralized trial infrastructure so that we can mitigate some of these expenses. Complex trial designs like basket or platform trials sometimes require sophisticated data systems and regulatory oversight. That is a challenge. And I think some of the pragmatic studies like ASCO TAPUR have overcome those challenges. Advanced technologies like next-gen sequencing and molecular profiling also add significant upfront cost to this. Funding is also limited because rare cancers receive less attention compared to common cancers. Public funding and cooperative group trials help a lot, but I think they cannot cover everything. Patient advocacy organizations sometimes step in to bridge these gaps, but sustainable financing remains a huge challenge. So, the bottom line is without financial incentives and collaborating funding models, many promising therapies for rare cancers would never make it to patients. That is why we need system-wide policy changes, global partnerships, and innovative, effective, seamless trial designs which are so critical so that they can help reduce the cost and make research feasible so that we can deliver the right drug to the right patient at the right time. Dr. Hope Rugo: There is a lot of excitement about the future integration of AI in screening. Just at the San Antonio Breast Cancer meetings, we have a number of different presentations about AI to find markers, even like HER2, and using AI where you would screen and then match patients to clinical trials. Do you have any guidance for the rare cancer community on how to leverage this technology in order to optimize patient enrollment and, I think, identification of the best treatment matches? Dr. Vivek Subbiah: I think artificial intelligence, AI, is a game-changer in the making. Right now, clinical trial is clunky. Matching patients to trial is often manual, time consuming, laborious. You need a lot of personnel to do that. AI can automate this process by analyzing genomic data, medical records, and trial eligibility criteria to find the best matches quickly, accurately, and effectively. For the community, the key is to invest in data standardization and interoperability because AI needs clean, structured data to work effectively. Dr. Hope Rugo: Thank you so much, Dr. Subbiah, for sharing these fantastic insights with us on the podcast today and for your excellent article. Dr. Vivek Subbiah: Thank you so much. Dr. Hope Rugo: We thank you, our listeners, for joining us today. You will find a link to Dr. Subbiah's Educational Book article in the transcript of this episode. And please join us again next month on By the Book for more insightful views on key issues and innovations that are shaping modern oncology.  Thank you. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:        Dr. Hope Rugo   @hoperugo   Dr. Vivek Subbiah @VivekSubbiah Follow ASCO on social media:        ASCO on X  ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:       Dr. Hope Rugo:    Honoraria: Mylan/Viatris, Chugai Pharma   Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer   Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx   Dr. Vivek Subbiah: Consulting/Advisory Role: Loxo/Lilly, Illumina, AADI, Foundation Medicine, Relay Therapeutics, Pfizer, Roche, Bayer, Incyte, Novartis, Pheon Therapeutics, Abbvie Research Funding (Inst.): Novartis, GlaxoSmithKline, NanoCarrier, Northwest Biotherapeutics, Genentech/Roche, Berg Pharma, Bayer, Incyte, Fujifilm, PharmaMar, D3 Oncology Solutions, Pfizer, Amgen, Abbvie, Mutlivir, Blueprint Medicines, Loxo, Vegenics, Takeda, Alfasigma, Agensys, Idera, Boston Biomedical, Inhibrx, Exelixis, Amgen, Turningpoint Therapeutics, Relay Therapeutics Other Relationship: Medscape, Clinical Care Options

In this episode of The Fertility Podcast, I'm joined by Hayley King, donor-conceived adult, mum of donor-conceived twins, and Operations Manager at Path to Parenthub. We're talking about the story that made headlines last December, a sperm donor with a genetic mutation linked to cancer being used in nearly 200 conceptions across 14 countries.This episode unpacks how this could happen, the gaps in donor regulation that allow it, and what this means for families. We also talk about the emotional, ethical, and logistical challenges of donor conception in a globalised industry, where the same donor can be used across borders with no international limits in place.Hayley brings both personal and professional insight into how families can make informed choices, why early disclosure matters, and what changes are urgently needed to protect the next generation.If you're on a donor conception path or supporting someone who is, this conversation is essential listening.What we discuss in this episode:Hayley's experience growing up as a donor-conceived person, and what shifted when she became a parent herselfWhy early disclosure matters and how secrecy shaped the mental health of donor-conceived people in the pastThe UK's 10-family donor limit and why it does not apply outside the UKHow one donor can be used in multiple countries with no tracking or shared systemThe story of one donor linked to a BRCA1 cancer gene being used in nearly 200 conceptionsWhat “family limits” really mean and why they are difficult to enforce globallyThe emotional weight of discovering you have 50 or even 100 donor siblingsHow sperm banks and clinics are often driven by profit rather than transparencyWhat questions prospective parents can ask their clinic or sperm bankWhy Path to Parent Hub was created as a safe space for donor conception familiesHayley's advice for parents, donors, and donor-conceived adults navigating identity and connectionA note on regulation and emotional safety:While advances in genetic screening are helpful, they are not foolproof. The issue is not just medical, it is ethical. Donors should not be used to create hundreds of families across continents.Without international family limits or shared tracking systems, donor-conceived people may unknowingly share genetics with a vast number of people worldwide. This impacts their sense of self, their safety in relationships, and their ability to connect the dots in their identity.As Hayley says, transparency matters. Families deserve accurate information and regulated systems that put people over profit.Let's keep the conversation going:Follow me on Instagram: @fertilitypoddy

JCO PO author Dr. Shilpa Gupta at Cleveland Clinic Children's Hospital shares insights into her article, "Fibroblast Growth Factor Receptor 3 (FGFR3) Alteration Status and Outcomes on Immune Checkpoint Inhibitors (ICPI) in Patients with Metastatic Urothelial Carcinoma". Host Dr. Rafeh Naqash and Dr. Gupta discuss how FGFR3 combined with TMB emerged as a biomarker that may be predictive for response to ICPI in mUC. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and Associate Professor at the OU Health Stephenson Cancer Center. Today I am excited to be joined by Dr. Shilpa Gupta, Director of Genitourinary Medical Oncology at the Cancer Institute and co-leader of the GU Oncology Program at the Cleveland Clinic, and also lead author of the JCO PO article titled "Fibroblast Growth Factor Receptor 3 Alteration Status and Outcomes on Immune Checkpoint Inhibitors in Patients With Metastatic Urothelial Carcinoma." At the time of this recording, our guest's disclosures will be linked in the transcript. Shilpa, welcome again to the podcast. Thank you for joining us today. Dr. Shilpa Gupta: Thank you, Rafeh. Honor to be here with you again. Dr. Rafeh Naqash: It is nice to connect with you again after two years, approximately. I think we were in our infancy of our JCO PO podcast when we had you first time, and it has been an interesting journey since then. Dr. Shilpa Gupta: Absolutely. Dr. Rafeh Naqash: Well, excited to talk to you about this article that you published. Wanted to first understand what is the genomic landscape of urothelial cancer in general, and why should we be interested in FGFR3 alterations specifically? Dr. Shilpa Gupta: Bladder cancer or urothelial cancer is a very heterogeneous cancer. And while we find there is a lot of mutations can be there, you know, like BRCA1, 2, in HER2, in FGFR, we never really understood what is driving the cancer. Like a lot of old studies with targeted therapies did not really work. For example, we think VEGF can be upregulated, but VEGF inhibitors have not really shown definite promise so far. Now, FGFR3 receptor is the only therapeutic target so far that has an FDA approved therapy for treating metastatic urothelial cancer patients, and erdafitinib was approved in 2019 for patients whose tumors overexpressed FGFR3 mutations, alterations, or fusions. And in the landscape of bladder cancer, it is important because in patients with non-muscle invasive bladder cancer, about 70 to 80% patients can have this FGFR3. But as patients become metastatic, the alterations are seen in, you know, only about 10% of patients. So the clinical trials that got the erdafitinib approved actually used archival tumor from local cancer. So when in the real world, we don't see a lot of patients if we are trying to do metastatic lesion biopsies. And why it is important to know this is because that is the only targeted therapy available for our patients right now. Dr. Rafeh Naqash: Thank you for giving us that overview. Now, on the clinical side, there is obviously some interesting data for FGFR3 on the mutation side and the fusion side. In your clinical practice, do you tend to approach these patients differently when you have a mutation versus when you have a fusion? Dr. Shilpa Gupta: We can use the treatment regardless of that. Dr. Rafeh Naqash: I recently remember I had a patient with lung cancer, squamous lung cancer, who also had a synchronous bladder mass. And the first thought from multiple colleagues was that this is metastatic lung. And interestingly, the liquid biopsy ended up showing an FGFR3-TACC fusion, which we generally don't see in squamous lung cancers. And then eventually, I was able to convince our GU colleagues, urologists, to get a biopsy. They did a transurethral resection of this tumor, ended up being primary urothelial and synchronous lung, which again, going back to the FGFR3 story, I saw in your paper there is a mention of FGFR3-TACC fusions. Anything interesting that you find with these fusions as far as biology or tumor behavior is concerned? Dr. Shilpa Gupta: We found in our paper of all the patients that were sequenced that 20% had the pathognomonic FGFR3 alteration, and the most common were the S249C, and the FGFR3-TACC3 fusion was in 45 patients. And basically I will say that we didn't want to generate too much as to fusion or the differences in that. The key aspect of this paper was that historically there were these anecdotal reports saying that patients who have FGFR alterations or mutations, they may not respond well to checkpoint inhibitors because they have the luminal subtype. And these were backed by some preclinical data and small anecdotal reports. But since then, we have seen that, and that's why a lot of people would say that if somebody's tumor has FGFR3, don't give them immunotherapy, give them erdafitinib first, right? So then we had this Phase 3 trial called the THOR trial, which actually showed that giving erdafitinib before pembrolizumab was not better. That debunked that myth, and we are actually reiterating that because in our work we found that patients who had FGFR3 alterations or fusions, and if they also have TMB-high, they actually respond very well to single agent immunotherapy. And that is, I think, very important because it tells us that we are not really seeing that so-called potential of resistance to immunotherapy in these patients. So to answer your question, yeah, we did see those differences, but I wouldn't say that any one marker is more prominent. Dr. Rafeh Naqash: The analogy is kind of similar to what we see in lung cancer with these mutations called STK11/KEAP1, which are also present in some other tumors. And one of the questions that I don't think has been answered is when you have in lung cancer, if you extrapolate this, where doublet or single agent immunotherapy doesn't do as well in tumors that are STK11 mutated. But then if you have a high TMB, question is does that TMB supersede or trump the actual mutation? Could that be one reason why you see the TMB-high but FGFR3 altered tumors in your dataset responding or having better outcomes to immunotherapy where potentially there is just more neoantigens and that results in a more durable or perhaps better response to checkpoint therapy? Dr. Shilpa Gupta: It could be. But you know, the patients who have FGFR alterations are not that many, right? So we have already seen that just patients with TMB-high respond very well to immunotherapy. Our last podcast was actually on that, regardless of PD-L1 that was a better predictor of response to immunotherapy. So I think it's not clear if this is adding more chances of response or not, because either way they would respond. But what we didn't see, which was good, that if they had FGFR3, it's not really downplaying the fact that they have TMB-high and that patients are not responding to immunotherapy. So we saw that regardless, and that was very reassuring. Dr. Rafeh Naqash: So if tomorrow in your clinic you had an individual with an FGFR3 alteration but TMB-high, I guess one could be comfortable just going ahead with immunotherapy, which is what the THOR trial as you mentioned. Dr. Shilpa Gupta: Yes, absolutely. And you know, when you look at the toxicity profiles of pembrolizumab and erdafitinib, really patients really struggle with using the FGFR3 inhibitors. And of course, if they have to use it, we have to, and we reserve it for patients. But it's not an easy drug to tolerate. Currently the landscape is such that, you know, frontline therapy has now evolved with an ADC and immunotherapy combinations. So really if patients progress and have FGFR3 alterations, we are using erdafitinib. But let's say if there were a situation where a patient has had chemotherapy, no immunotherapy, and they have FGFR3 upregulation and TMB-high, yes, I would be comfortable with using only pembrolizumab. And that really ties well together what we saw in the THOR trial as well. Dr. Rafeh Naqash: Going to the clinical applications, you mentioned a little bit of this in the manuscript, is combination therapies. You alluded to it a second back. Everything tends to get combined with checkpoint therapy these days, as you've seen with the frontline urothelial, pembrolizumab with an ADC. What is the landscape like as far as some of these FGFR alterations are concerned? Is it reasonable to combine some of those drugs with immune checkpoint therapy? And what are some of the toxicity patterns that you've potentially seen in your experience? Dr. Shilpa Gupta: So there was indeed a trial called the NORSE trial. It was a randomized trial but not a comparative cohort, where they looked at FGFR altered patients. And when they combined erdafitinib plus cetrelimab, that did numerically the response rates were much higher than those who got just erdafitinib. So yeah, the combination is definitely doable. There is no overlapping toxicities. But unfortunately that combination has not really moved forward to a Phase 3 trial because it's so challenging to enroll patients with such kind of rare mutations on large trials, especially to do registration trials. And since then the frontline therapy has evolved to enfortumab vedotin and pembrolizumab. I know there is an early phase trial looking at a next generation FGFR inhibitor. There is a triplet combination looking in Phase 1 setting with a next generation FGFR inhibitor with EV-pembro. However, it's not a randomized trial. So you know, I worry about such kinds of combinations where we don't have a path for registration. And in the four patients that have been treated, four or five patients in the early phase as a part of basket trial, the toxicities were a lot, you know, when you combine the EV-pembro and an FGFR3 inhibitor, we see more and more toxicity. So the big question is do we really need the "kitchen sink" approach when we have a very good doublet, or unless the bar is so high with the doublet, like what are we trying to add at the expense of patient toxicity and quality of life is the big question in my mind. Dr. Rafeh Naqash: Going back to your manuscript specifically, there could be a composite biomarker. You point out like FGFR in addition to FGFR TMB ends up being predictive prognostic there. So that could potentially be used as an approach to stratify patients as far as treatment, whether it's a single agent versus combination. Maybe the TMB-low/FGFR3 mutated require a combination, but the TMB-high/FGFR mutated don't require a combination, right? Dr. Shilpa Gupta: No, that's a great point, yeah. Dr. Rafeh Naqash: But again, very interesting, intriguing concepts that you've alluded to and described in this manuscript. Now, a quick take on how things have changed in the bladder cancer space in the last two years. We did a podcast with you regarding some biomarkers as you mentioned two years back. So I really would like to spend the next minute to two to understand how have things changed in the bladder cancer space? What are some of the exciting things that were not there two years back that are in practice now? And how do you anticipate the next two years to be like? Maybe we'll have another podcast with you in another two years when the space will have changed even more. Dr. Shilpa Gupta: Certainly a lot has happened in the two years, you know. EV-pembro became the universal frontline standard, right? We have really moved away from cisplatin eligibility in metastatic setting because anybody would benefit from EV-pembro regardless of whether they are candidates for cisplatin or not, which historically was relevant. And just two days ago, we saw that EV-pembro has now been approved for localized bladder cancer for patients who are cisplatin ineligible or refusing. So, you know, this very effective regimen moving into earlier setting, we now have to really think of good treatment options in the metastatic setting, right? So I think that's where a lot of these novel combinations may come up. And what else we've seen is in a tumor agnostic trial called the DESTINY-PanTumor trial, patients who had HER2 3+ on immunohistochemistry, we saw the drug approval for T-DXd, and I think that has kind of reinvigorated the interest in HER2 in bladder cancer, because in the past targeting HER2 really didn't work. And we still don't know if HER2 is a driver or not. And at ESMO this year, we saw an excellent study coming out of China with DV which is targeting HER2, and toripalimab, which is a Chinese checkpoint inhibitor, showing pretty much similar results to what we saw with EV-pembro. Now, you know, not to do cross-trial comparisons, but that was really an amazing, amazing study. It was in the presidential session. And I think the big question is: does that really tell us that HER2-low patients will not benefit? Because that included 1+, 2+, 3+. So that part we really don't know, and I think we want to study from the EV-302 how the HER2 positive patients did with EV and pembro. So that's an additional option, at least in China, and hopefully if it gets approved here, there is a trial going on with DV and pembro. And lastly, we've seen a very promising biomarker, like ctDNA, for the first time in bladder cancer in the adjuvant setting guiding treatment with adjuvant atezolizumab. So patients who were ctDNA positive derived overall survival and recurrence-free survival benefit. So that could help us select moving forward with more studies. We can spare unnecessary checkpoint inhibitors in patients who are not going to benefit. So I think there is a lot happening in our field, and this will help do more studies because we already have the next generation FGFR inhibitors which don't have the toxicities that erdafitinib comes with. And combining those with these novel ADCs and checkpoint inhibitors, you know, using maybe TMB as a biomarker, because we really need to move away from PD-L1 in bladder cancer. It's shown no utility whatsoever, but TMB has. Dr. Rafeh Naqash: Well, thank you so much, Shilpa, for that tour de force of how things have changed in bladder cancer. There used to be a time when lung and melanoma used to lead this space in terms of the number of approvals, the biomarker development. It looks like bladder cancer is shifting the trend at this stage. So definitely exciting to see all the new changes that are coming up. I'd like to spend another minute and a half on your career. You've obviously been a leader and example for many people in the GU space and beyond. Could you, for the sake of our early career especially, the trainees and other listeners, describe how you focused on things that you're currently leading as a leader, and how you shaped your career trajectory over the last 10 years? Dr. Shilpa Gupta: That's a really important question, Rafeh, and you and I have had these discussions before, you know, being an IMG on visas like you, and being in different places. I think I try to make the most of it, you know, instead of focusing on the setbacks or the negative things. Like tried to grab the opportunities that came along. When I was at Moffitt, got to get involved with the Phase 1 trial of pembrolizumab in different tumor types. And just keeping my options open, you know, getting into the bladder cancer at that time when I wanted to really do only prostate, but it was a good idea for me to keep my options open and got all these opportunities that I made use of. I think an important thing is to, like you said, you know, have a focus. So I am trying to focus more on biomarkers that, you know, we know that 70% patients will respond to EV-pembro, right? But what about the remaining 30%? Like, so I'm really trying to understand what determines hyperprogressors with such effective regimens who we really struggle with in the clinic. They really don't do well with anything we give them after that. So we are doing some work with that and also trying to focus on PROs and kind of patient-reported outcomes. And a special interest that I've now developed and working on it is young-onset bladder cancer. You know, the colorectal cancer world has made a lot of progress and we are really far behind. And bladder cancer has historically been a disease of the elderly, which is not the case anymore. We are seeing patients in their 30s and 40s. So we launched this young-onset bladder cancer initiative at a Bladder Cancer Advocacy Network meeting and now looking at more deep dive and creating a working group around that. But yeah, you know, I would say that my philosophy has been to just take the best out of the situation I'm in, no matter where I am. And it has just helped shape my career where I am, despite everything. Dr. Rafeh Naqash: Well, thank you again. It is always a pleasure to learn from your experiences and things that you have helped lead. Appreciate all your insights, and thank you for publishing with JCO PO. Hopefully we will see more of your biomarker work being published and perhaps bring you for another podcast in a couple of years. Dr. Shilpa Gupta: Yeah, thank you, Rafeh, for the opportunity. And thanks to JCO PO for making these podcasts for our readers. So thanks a lot. Dr. Rafeh Naqash: Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcast. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. DISCLOSURES Dr. Shilpa Gupta Stock and Other Ownership Interests: Company: BioNTech SE,  Nektar Consulting or Advisory Role: Company: Gilead Sciences, Pfizer, Merck, Foundation Medicine, Bristol-Myers Squibb/Medarex, Natera, Astellas Pharma, AstraZeneca, Novartis, Johnson & Johnson/Janssen Research Funding: Recipient: Your Institution Company: Bristol Myers Squibb Foundation, Merck, Roche/Genentech, EMD Serono, Exelixis, Novartis, Tyra Biosciences, Pfizer, Convergent Therapeutics, Acrivon Therapeutics, Flare Therapeutics, Amgen Travel, Accommodations, Expenses: Company: Pfizer, Astellas Pharma, Merck    

"I had this sense of nostalgia, of we're going to look back on this as something special. We all felt a little bit of something magical going on." She's come a long way, baby! Jenny Grimshaw returns to the Ali on the Run Show, this time as a 2:32 marathoner. Jenny just ran four-minute personal best at the California International Marathon, qualifying for the 2028 Olympic Marathon Trials with room to spare. This is the same Jenny who spent years trying to break three hours. The Jenny with a long history of race anxiety. The Jenny who dropped out of CIM in 2022. In this episode, Jenny, a mom to two young kids who lives in San Francisco and works full-time, talks about how she made that 2:32:50 happen, and how she has kept chipping away at her marathon time and enjoying herself along the way. Jenny also has the BRCA1 gene: She had a preventative prophylactic double mastectomy a few years ago, and will have her ovaries removed next year.  FOLLOW JENNY @jenny_gshaw SPONSOR:  New Balance: Click here to get your hands on the fan favorite Rebel v5! Lagoon: Click here to take Lagoon's 2-minute sleep quiz to see which pillow is right for you, and take advantage of Lagoon's holiday sale, happening now! In this episode: Jenny's snapshot moment from CIM 2025 (2:50) All about Peninsula Distance Club, and the power of female friendships (5:20) How Jenny fits running and training into her days, and on learning to get over mom guilt (10:00) How being a mom has made Jenny a better runner (15:15) What it felt like to run a 2:32 marathon (17:40) How Jenny reacted when, at six weeks postpartum, she learned that the Trials standards had changed from 2:45 to 2:37 (21:10) On running 2:36 at the London Marathon this year — before the OTQ window opened for 2028 (25:50) How Jenny has navigated big running dreams and family planning (27:40) The decision not to run this year's Chicago Marathon, and why Jenny chose to do CIM instead (30:20) How Jenny knew it was going to be a special day at CIM (34:20) What it felt like standing on the CIM start line, and Jenny's goals for the day (38:30) What happens when the CIM finish line clock hits 2:37 (50:00) What's next for Jenny on the run (51:10) How Jenny is feeling about needing to have her ovaries removed as a result of having the BRCA1 gene (55:15) Jenny's advice for people who have big goals and dreams and are feeling stuck (58:20) All about Jenny's job at Equip, which provides virtual eating disorder treatment (1:00:15) Follow Ali: Instagram @aliontherun1 Join the Facebook group Support on Patreon Subscribe to the newsletter SUPPORT the Ali on the Run Show! If you're enjoying the show, please subscribe and leave a rating and review on Apple Podcasts. Spread the run love. And if you liked this episode, share it with your friends!

This episode brings together the science, the medicine, and the lived experience behind BRCA mutations.  Emily Goldberg, JScreen's Director of Genetic Counseling Services, breaks down what these mutations are, how they're inherited, and what the actual cancer risks look like. Dr. Melissa Frey, a GYN oncologist at Cornell who works closely with high-risk families, walks us through what happens after someone tests positive — from screening to risk-reducing surgeries to the big conversations around fertility and timing. We also hear from Heather Boussi, who shares her powerful story of living with both BRCA1 and BRCA2 mutations. She talks about diagnosis, surveillance, surgeries, and how this all shaped her family-building decisions. Lastly, we look at what BRCA means for men, how that journey differs, and why PGT can still be an option. If you or someone you love is navigating this, we close with places to turn for support: JScreen, Sharsheret, I Was Supposed To Have A Baby, and Stardust (links below). It's a mix of expertise, honesty, and heart — the kind of conversation so many people wish they had heard earlier, especially when faced with such difficult decisions.  Note: This episode is the 4th of a series of 5 that we are collaborating on with Jscreen in 2025.  Take a look at our previous three episodes here : Episode 157: Introduction to Genetics and Infertility Episode 166: Fragile X Syndrome: A Silent Factor in Infertility Episode 185: It's Not Just Her: Male Factor Fertility and Genetics Uncovered Resources: Genetics and Personalized Cancer Prevention Program Facing Our Risk Empowered (FORCE) Jewish Fertility Foundation Stardust Foundation Sharsheret JScreen More about Emily Goldberg: Emily Goldberg serves as the Director of Genetic Counseling Services at jscreen, where she is dedicated to helping individuals understand and manage their genetic health. With dual bachelor's degrees in biology and psychology from Brandeis University and a master's degree in Human Genetics from Sarah Lawrence College, Ms. Goldberg has been a certified genetic counselor since 2011. Prior to joining jscreen, she worked at Montefiore Medical Center in the Bronx, specializing in prenatal and cancer genetics. In addition to her role at jscreen, Ms. Goldberg is committed to education, serving as an Instructor at the Albert Einstein College of Medicine and adjunct faculty at Sarah Lawrence College, where she teaches and mentors future genetic counselors. Her expertise and dedication make her a key member of the jscreen team. Connect with JScreen: - visit their website here - check out their Instagram   More about Melissa Frey, MD: Dr. Melissa Frey is an Associate Professor of Obstetrics and Gynecology in the division of Gynecologic Oncology and the Director of the Genetics and Personalized Cancer Prevention Program at Weill Cornell Medicine / NewYork Presbyterian Hospital. Dr. Frey's clinical care and research focus on the management of individuals with hereditary cancer syndromes (e.g. BRCA1, BRCA2, Lynch syndrome) and strong family history of breast and gynecologic cancers. She performs gynecologic cancer risk-reducing surgeries and is the principal investigator on several large trials aimed at cancer prevention among high-risk individuals. Dr. Frey has presented her research at national and international meetings and has more than 130 publications in peer-reviewed scientific journals. Connect with Dr. Melissa Frey: - check out her Instagram - view the Genetics and Personalized Cancer Prevention Program website   More about Heather Boussi :  Heather grew up in Westchester, NY and now lives in Englewood, NJ with her husband and three children. Her personal experience with hereditary cancer risk and genetic testing has made her a passionate advocate for awareness, education, and empowerment in women's health. Grounded in faith and family, Heather shares her story to help others approach life's challenges with strength, perspective, and gratitude. Connect with Heather: - check out Heather's Instagram   Connect with us: -Check out our Website -Follow us on Instagram and send us a message -Watch our TikToks -Follow us on Facebook -Watch us on YouTube -Connect with us on LinkedIn

Peter Van Valkenburgh is the Executive Director of Coin Center, a leading nonprofit research and advocacy group focused on cryptocurrency policy. In this episode, Peter joins The Bitcoin Frontier to explore why defending the right to self-custody is about much more than bitcoin — it's about the future of individual freedom, open-source innovation, and financial privacy. We dig into the parallels between the 1990s “crypto wars” and today's digital sovereignty battles, the threats facing developers of privacy tools, and the constitutional foundations for privacy and property in the digital age.SUPPORT THE PODCAST: → Subscribe → Leave a review → Share the show with your friends and family → Send us an email: podcast@unchained.com → Learn more about Unchained: https://unchained.com/?utm_source=you... → Book a free call with a bitcoin expert: https://unchained.com/consultation?ut...TIMESTAMPS:0:00 – Intro and Peter's journey from acting to bitcoin policy2:00 – Discovering the cypherpunks and the roots of internet freedom4:00 – Entering bitcoin through law school and meeting Jerry Brito6:00 – Founding Coin Center and defining “permissionless innovation”9:00 – The mission: protecting the freedom to build and use open blockchains11:00 – Bitcoin's privacy problem and the legal risks of building privacy tech13:00 – Educating DC: explaining bitcoin to Congress in the early days16:00 – Navigating the SEC, ICOs, and defining what counts as a security18:30 – The evolution from education to constitutional litigation22:00 – Bitcoin as the revival of a “bearer instrument” economy26:00 – The “secret right to cash” and the Fourth Amendment's blind spot30:00 – Privacy, property, and what bitcoin reveals about constitutional limits35:00 – The Keep Your Coins Act and why it matters for financial sovereignty43:00 – The DOJ's shift toward prosecuting developers — and why it's dangerous46:00 – Inside the Tornado Cash and Samurai Wallet prosecutions50:00 – How Coin Center is fighting for software publishing rights54:00 – Legislative progress: Clarity, Keep Your Coins, and BRCA1:00:00 – Lessons from the 1990s encryption wars1:03:00 – How liability protections shaped (and centralized) the internet1:08:00 – The convenience dilemma: why self-custody must become easier1:12:00 – The Bank Secrecy Act, mass surveillance, and new legal challenges1:19:00 – Coin Center's constitutional lawsuits for privacy and association rights1:23:00 – Why the BSA is ripe for reform — and bitcoin's role in that debate1:27:00 – Zero-knowledge proofs, AML, and a future of privacy-preserving compliance1:29:00 – How self-custody wallets enable digital identity and personal sovereignty1:31:00 – Closing thoughts: bitcoin as the foundation for a freer digital futureWHERE TO FOLLOW US: → Unchained X: https://x.com/unchained → Unchained LinkedIn:   / unchainedcom  → Unchained Newsletter: https://unchained.com/newsletter → Joe Kelly's Twitter: https://x.com/josephkelly → Peter Van Valkenburgh's Twitter: https://x.com/valkenburgh 

On this episode of the Healthful Woman Podcast, Dr. Fox continues his discussion with Jordanna Nadritch, President of Sharsheret's Board of Directors. She shares her journey as a BRCA1 previvor, navigating multiple surgeries, raising young children, and finding healing through volunteering and connecting with others. She reflects on the power of sharing her story, giving back, and honoring her mother's legacy while discovering her own resilience.

Dr Matt Burgess talks with Mary-Anne Young about the real-world impact of genomics on healthcare and genetic counselling. They cover BRCA1/2 history, rapid testing, integration with oncology, and using polygenic risk to personalise care. The episode explores family systems and counselling techniques, ethical issues around returning research findings, workforce diversity, and practical steps to implement genomic advances in clinics. Listeners will get a concise look at how genomics is changing patient care, communication with families, and the direction of the genetic counselling profession.

On this episode of the Healthful Woman Podcast, Dr. Fox speaks with Jordanna Nadritch, President of Sharsheret's Board of Directors. Jordanna shares her mother's battle with aggressive breast cancer, her own BRCA1 diagnosis, and the difficult choice to undergo a double mastectomy at just 34. With honesty and strength, she reflects on how her mother's story ultimately saved her life and inspired her path to advocacy and leadership within Sharsheret.

Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago. In this episode, OncLive On Air® partnered with Two Onc Docs to feature a comprehensive review of the current management of metastatic breast cancer, emphasizing evidence-based treatment strategies across molecular subtypes, toxicity management, and patient-centered care. Drs Armstrong and Tawagi discussed that the primary goals of metastatic breast cancer therapy include prolonging survival, controlling symptoms, minimizing toxicity, improving quality of life, and incorporating patients' goals and preferences into care decisions. Their discussion also highlighted the importance of recognizing when transitioning to best supportive care is most appropriate. For estrogen receptor–positive metastatic breast cancer, they noted that first-line therapy includes an aromatase inhibitor or fulvestrant (Faslodex) combined with a CDK4/6 inhibitor, with ovarian function suppression for premenopausal patients. PARP inhibitors are recommended for patients with BRCA1/2-positive disease. In visceral crisis, chemotherapy remains the category 1 recommendation. Second-line treatment options include therapies guided by repeat molecular testing. fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) is approved for patients with HER2-low disease. For HER2-positive metastatic breast cancer, first-line treatment consists of a taxane plus pertuzumab (Perjeta) and trastuzumab (Herceptin), followed by T-DXd in the second-line setting. For triple-negative metastatic breast cancer, therapy depends on PD-L1 status. The episode concluded by underscoring the role of bone-protective agents such as zoledronic acid, pamidronate, or denosumab (with dental clearance to prevent osteonecrosis). Key takeaways emphasize tailoring therapy to molecular subtype, recognizing drug-specific toxicities, and prioritizing patient-centered decision-making in the management of metastatic breast cancer.

Send us a textA stomach that feels “off” can be easy to brush aside—until it shouldn't be. In this episode, Cara and Missi dig into the quiet warning signs of ovarian disease, separating the everyday from the rare but dangerous ovarian pathology. You'll learn how to read the body's cues using the BEAT mnemonic (Bloating, Early satiety, Abdominal/pelvic pain, Trouble with urination or bowels), what ultrasound reports actually mean, and why most ovarian cysts are benign even as we stay alert to red flags.We walk through the physiology of the menstrual cycle—why ovulation naturally creates a cyst each month—and how that helps explain functional cysts that disappear on their own. Then we shift to the features that raise concern: septations, solid components, irregular borders, and blood flow on Doppler. We talk openly about the limits of CA125, the absence of a reliable screening test, and why surgical biopsy still anchors a definitive diagnosis.  We unpack how opportunistic salpingectomy at the time of hysterectomy or permanent sterilization can cut risk, and how combined oral contraceptives lower lifetime risk by suppressing ovulation. We also cover who needs genetic counseling—BRCA1/2, Lynch syndrome, and other familial cancer clues—and how to build smart follow-up plans that balance reassurance with action. Most ovarian findings are benign; the key is knowing when to watch and when to act. If this conversation helps you or a patient put a name to a nagging symptom, it's done its job. 

You've probably heard of cancer survivors, but have you heard of previvors? These are women with genetic mutations like BRCA1, BRCA2, or CHECK2 who are at higher risk for cancer but don't have it yet. October is both Breast Cancer Awareness Month and Menopause Awareness Month, making it the perfect time to discuss genetic testing, cancer risk assessment, and what previvors need to know about their options.Using a 28-year-old patient with CHECK2 mutation as an example, I walk through when genetic testing makes sense, how to calculate your lifetime risk, and what screening protocols change when your risk is elevated. I cover modifiable lifestyle factors that account for 30% of breast cancer cases, including alcohol intake, diet, exercise, and optimal body weight. The key message: genetic testing is about empowerment and prevention, not fear.I also address surgical menopause after risk-reducing procedures. When you remove ovaries in your 30s or 40s to prevent cancer, you fall off a hormonal cliff with immediate consequences. The critical issue: estrogen therapy is NOT contraindicated for previvors without personal cancer history, yet surgical patients are rarely given a menopause plan before going under anesthesia. Early estrogen loss increases cardiovascular disease, dementia, osteoporosis, and all-cause mortality risks.Highlights:What CHECK2, BRCA1/2, and other mutations mean for lifetime cancer risk.How removing ovaries before age 45 without HRT increases all-cause mortality risk.Why previvors without cancer CAN and SHOULD take estrogen after preventative surgery.Why you should demand a menopause plan BEFORE risk-reducing surgery, not after.If this episode empowered you to have conversations about family history and genetic testing, or helped you understand why hormone replacement matters after preventative surgery, please share it with women who need this information. Subscribe and leave a review to help more people discover these critical discussions about cancer prevention and quality of life.Get in Touch with me: WebsiteInstagramYoutubeSubstackMentioned in this episode:GSM CollectiveThe GSM Collective - Chicago Boutique concierge gynecology practice Led by Dr. Sameena Rahman, specialist in sexual medicine & menopause Unrushed appointments in a beautiful, private setting Personalized care for women's health, hormones, and pelvic floor issues Multiple membership options available Ready for personalized women's healthcare? Visit our Chicago office today. GSM CollectiveGSM CollectiveThe GSM Collective - Chicago Boutique concierge gynecology practice Led by Dr. Sameena Rahman, specialist in sexual medicine & menopause Unrushed appointments in a beautiful, private setting Personalized care for women's health, hormones, and pelvic floor issues Multiple membership options available Ready for personalized women's healthcare? Visit our Chicago office today. GSM Collective

JCO PO author Dr. Bryson Katona at the University of Pennsylvania Perelman School of Medicine shares insights into his article, “Areas of Uncertainty in Pancreatic Cancer Surveillance: A Survey Across the International Pancreatic Cancer Early Detection (PRECEDE) Consortium” Host Dr. Rafeh Naqash and Dr. Katona discuss how, given differing guidelines as well as lack of detail about how PC surveillance should be performed, approaches to PC surveillance across centers often differs. TRANSCRIPT Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I am your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and Associate Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today, I am thrilled to be joined by Dr. Bryson Katona, Director of the Gastrointestinal Cancer Genetics Program and Director of the Lynch Syndrome Program at the Penn Medicine's Abramson Cancer Center, and also lead author of the JCO PO article entitled "Areas of Uncertainty in Pancreatic Cancer Surveillance: A Survey Across the International Pancreatic Cancer Early Detection or PRECEDE Consortium." Bryson, thanks for joining us again. Dr. Bryson Katona: Well, thank you so much for having me. I appreciate the opportunity. Dr. Rafeh Naqash: It is exciting to see that this work will be presented concurrently with the upcoming CGA meeting. Dr. Bryson Katona: Yes, it has been a fantastic partnership between JCO PO and the CGA-IGC and their annual meeting. And for those who may not be familiar, the CGA-IGC is the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer. It is basically a professional organization dedicated to individuals who have hereditary GI cancer risk and focusing on providing education, promoting research, and really bringing together providers in this space from not just throughout the US but from across the globe as well. Dr. Rafeh Naqash: That is exciting to hear the kind of work you guys are doing. These are definitely interesting, exciting things. Now, going to what you have published, it is an area that is very evolving in the space of cancer screening, cancer surveillance, especially for a very aggressive cancer such as pancreatic cancer. Could you tell us currently, what are the general consensus? I know there are a lot of differences between different guidelines or societies, but what are the some of the commonalities if we were to start there first for pancreas cancer screening? If you are not a GI oncologist, you may not be aware that there is something with regards to pancreas cancer screening. Could you give us an overview and a background on that? Dr. Bryson Katona: Yeah, I think that pancreatic cancer screening really is one of the most controversial areas of all cancer screening. Part of that controversy is just because all the guidelines, the many different guidelines that are out there, do not always match up with one another, which I think leads to a lot of confusion, not just for providers but for patients who are trying to go through this, and then also the insurance companies in trying to get these screening tests covered. You know, when we think about who is eligible for pancreatic cancer screening, you know, it is important that these are not average-risk individuals. So really, we are only offering screening to high-risk individuals. And those can include people that have a strong family history of pancreatic cancer without a germline genetic susceptibility that has been identified. And those individuals we refer to as having familial pancreatic cancer. And the other big cohort is those individuals that carry hereditary pancreatic cancer predisposition. These are due to cancer risk mutations in many different genes, including many of the breast cancer risk genes like BRCA1 and BRCA2, as well as ATM and PALB2, but then other genes such as the Lynch syndrome genes, and then some of the higher risk genes such as those leading to Peutz-Jeghers syndrome as well as FAM, which is due to CDKN2A mutations. Dr. Rafeh Naqash: Thank you for that. Again, another practical question, and this may or may not be exactly related to your specific topic here, but perhaps to some extent there might be an overlap. If I get a patient from a colleague, and I see people in the early-phase clinical trial setting, so many different tumors for novel drugs, and I find an individual with, let us say, lung cancer who has a pathogenic BRCA2, which is somatic, should I be worried about pancreas cancer screening in that individual? Or have we not met that threshold yet in that circumstance? Dr. Bryson Katona: A lot of times these variants or these genes that are associated with pancreatic cancer risk get picked up on the somatic tumor profiles. Now, you know, whether or not those are truly germline variants typically requires the next step of referring the patient for germline genetic testing. So you know, I would not screen or make any kind of screening choices based on a somatic variant alone, but nowadays germline testing is so easy, so efficient, and relatively cheap that it is easy enough to confirm whether or not these somatic hits are in fact just somatic or may confer some germline risk in addition. Dr. Rafeh Naqash: So from what I understand from what you have said, there is debate about it, but it is something that should be done or is important enough that you need to figure out a path moving forward. Was that one of the reasons why you performed this project through this very interesting consortium called the PRECEDE Consortium? Dr. Bryson Katona: Yeah, that was one of our main reasons for doing this. And for those who do not know about the PRECEDE Consortium, this is a very large international, multi-institutional organization really focused on reducing death and improving survival from pancreatic cancer, primarily through increased and more effective use of screening and early detection strategies. This is an international consortium. There are over 50 sites now with nearly 10,000 patients who are enrolled in the consortium. So it really is at this point the largest prospective study of individuals who are at high risk for pancreatic cancer who are undergoing screening. And you know, I think amongst all of us in the consortium, just amongst discussions between colleagues and then, you know, often times when I see patients that are transferring their care to Penn who maybe had their screening done in another center before, what we were realizing is that, you know, although we all do a lot of screening, it seems that people are doing it slightly differently. And it does not seem that there is a real consensus approach across all centers about how pancreatic cancer screening should really be done. And it is one thing if you are thinking comparing, okay, well, maybe in the US we do it differently than, you know, in Europe or in other locations, but even among centers within the United States, we were still seeing very large differences in how pancreatic cancer screening in high-risk individuals were done. And so that led us to really pursue this survey of pancreatic cancer screening practices across the PRECEDE Consortium. So for this survey, we actually have 57 centers who the survey was sent out to. As you know, surveys are oftentimes very difficult to get good response rates back on, but we were fortunate to have 54 of the 57, or 95% of the centers, actually get back to us about their screening practices for this particular project. Dr. Rafeh Naqash: That is good to know. I hope you did not have to use any kind of gift cards for people to respond to the survey. But nevertheless, you got the information that you needed. Could you tell us what are some of the common denominators that you did identify and some of the differences that you identified? From your perspective, it sounds like there is no established consensus guidelines. There are different societies that have different perspectives on it. So I am sure some of what you found will probably have implications in maybe creating some guidelines. Is that a fair statement? Dr. Bryson Katona: Definitely a fair statement, and we found some very interesting results. I think one important result is really just the heterogeneity in the consortium. And so even before we got into pancreatic cancer screening practices, we also, we were asking consortium sites, “At your particular site, who is the individual that is leading these in-depth discussions about pancreatic cancer screening?” And while about 50% of the sites had a gastroenterologist leading it, about a quarter of the sites had a medical oncologist, a quarter had a surgeon leading these discussions as well. And we also found heterogeneity in who is the physician or the provider actually ordering these screening tests, again, with multiple different specialties across the different sites. But really one of the main areas that we wanted to hone in and focus on was how the different pancreatic cancer screening guidelines were actually utilized in each of the particular centers. The biggest controversial area in the field is for the gene mutation carriers, whether or not we should be requiring that a family history of pancreatic cancer be present in order for those individuals to qualify for pancreatic cancer screening. And the reason that is so controversial, let us take an example of BRCA1 and BRCA2 carriers. Currently, if you look through the guidelines, NCCN and the ASGE guidelines recommend that really all BRCA2 carriers undergo pancreatic cancer screening regardless of whether or not there is a family history, starting at age 50. However, other guidelines such as the AGA guidelines, or the AGA Clinical Practice Statement, as well as guidelines from the CAPS consortium, do recommend that a family history of pancreatic cancer be present in order to qualify for screening. But then we have different things for other genes. So for BRCA1 carriers, in fact, it is the ASGE guidelines that recommend all BRCA1 and 2 carriers undergo screening, whereas NCCN and the other guidelines that are out there do not recommend those individuals undergo screening. Again, this huge heterogeneity in guidelines is quite striking. And so when we assessed all the sites in the PRECEDE Consortium, we found some really interesting results with respect to these particular genes. For BRCA2 carriers specifically, we found that about half of the sites required a family history for recommending pancreatic cancer screening, but about half of the sites would offer it to all BRCA2 carriers regardless of if there was a family history of pancreatic cancer screening. Rates for BRCA1, PALB2, and ATM carriers were a little bit lower, where about a third of sites would offer screening really regardless of whether or not there is a family history of pancreatic cancer. And for Lynch syndrome, those rates were very, very low, with only about 13% of sites offering screening to Lynch patients in the absence of a family history. But I think, you know, we are all in the same consortium, but there is still just a lot of heterogeneity in how our own individual practices are run. Dr. Rafeh Naqash: Definitely different thoughts, different practices. But from what you saw, did it matter as far as outcomes are concerned whether it was a gastroenterologist doing the screening, or it was a medical oncologist, or a geneticist? Or is it a combination of all of these that actually makes the most difference? Dr. Bryson Katona: So I think we do need to get some more information about specialty-specific screening preferences. We just had one response per site in this particular survey, and so I think we are going to need a larger sample size in order to get that data. But I think that is certainly possible that, you know, certain subspecialties may prefer, you know, screening more aggressively or not including family history. That is definitely a question that we will be asking in future studies. Dr. Rafeh Naqash: Definitely more gift cards that will be needed as well. Moving on to another aspect of the implications for early detection, from a breast cancer, colon cancer standpoint, there is health economics research that shows it saves cost in the bigger picture. Has there been anything for pancreas cancer where early detection, early identification, early treatment actually ends up saving a lot more versus detecting metastatic pancreas cancer later? Dr. Bryson Katona: It is a great question. And of course, for any screening modality, you know, we would ultimately want it to be a cost-effective measure. In pancreas cancer screening, the jury is still a little bit out about whether or not pancreas cancer screening is truly cost-effective or not. There have been several different studies that have assessed this. And I think in general, the thought is that it is a cost-effective endeavor. But I think most of these cost-effectiveness estimates are actually related to what is the risk of pancreatic cancer in the population you are studying. And so when you have very, very high-risk individuals that have over a 10% lifetime risk of pancreatic cancer, it is almost a certainty that pancreatic cancer screening is going to be cost-effective. However, you know, if you have, say for example, BRCA1 carriers where lifetime risk of pancreatic cancer may be less than 5%, likely around like 3%, those individuals, I think it is going to be a tougher sell to say that it is cost-effective. But as we get more data on pancreatic cancer screening, that will be a very important question to ask. And you know, when you mentioned how does it save money, our goal at least in pancreatic cancer screening is to really downstage pancreatic cancer at the time of diagnosis and allow someone to undergo, you know, ideally a curative-intent surgery. There is data out there showing that we can downstage the cancers, that survival after the time of diagnosis is substantially increased after detection in a pancreatic cancer screening program. But again, these are studies that are based on fairly small numbers of converters. And so I think we need more data in that space as well, which is one of the main questions that the PRECEDE Consortium is trying to answer with all of our prospective data. Dr. Rafeh Naqash: Excellent. Well, I hope we see more interesting, exciting work from the PRECEDE Consortium at meetings as well as as a publication in JCO PO. I would like to shift gears briefly for a minute or two, Bryson, to you as an individual, your career. How have you evolved over the last 5, 7 years? How did you end up doing cancer genetics? What were some of the lessons that you learned along the way and some of those that you would want to share with our listeners, especially trainees and early-career faculty? Dr. Bryson Katona: Just to give you and others listening a little bit of background, but I am a physician-scientist, gastroenterologist, but a physician-scientist. And so my clinical practice is exclusively focused on individuals with hereditary GI cancer risk. I run a basic science lab where we do a lot of studies in organoids and mouse models of these hereditary GI cancer risk syndromes. And then I also have a clinical research group where we do early-phase clinical trials and screening and early detection trials, again in these same individuals with hereditary GI cancer risk. I think probably the most important thing that kind of allowed me to get to this stage in my career where I am trying to, you know, essentially try to juggle all three of these balls at the same time is that I absolutely love what I do. And I am so incredibly interested in what I do. And I think for young individuals that are coming through the pipeline and going through training, you know, I mean, finding a specialty and a clinical niche where you truly just enjoy the work and you enjoy the patients and you enjoy your colleagues is by far the most important thing. I ended up getting into the hereditary GI cancer space because a lot of my work earlier on in my career during my PhD and then in my postdoc work in the lab really focused on colorectal cancer. And I thought that focusing on cancer genetics could allow me to really continue to think from the molecular side of things while simultaneously being a gastroenterologist and taking care of patients with hereditary cancer risk. Dr. Rafeh Naqash: Well, thank you so much for giving us a sneak peek of your journey and insights on what perhaps works best, especially when you love what you do. I think that is one of the most important reasons a work tries to keep you going and keep you interested, keep you passionate. So thank you again. Thank you for listening to JCO Precision Oncology Conversations. Do not forget to give us a rating or a review, and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Send us a textSeason 3 Episode 6New Episode: Amy Carroll – Strength, Resilience, and Life Beyond BRCA1In this episode, we sit down with Amy Carroll, a model and actor also known by her stage name Darcie Diamond. Amy shares her powerful journey of living with the BRCA1 gene mutation, which significantly increases the risk of breast and ovarian cancer.After making the life-changing decision to undergo a double mastectomy, Amy talks openly about resilience, identity, and how she continues to thrive in the worlds of modelling and acting. We explore the science behind BRCA1, what it means to inherit the mutation, and why genetic testing and early screening are vital tools for prevention and informed decision-making.This conversation is not only about genetics and medicine, but also about courage, self-discovery, and the strength it takes to embrace life after such a profound challenge.#HeartTransplant#eatingdisorder#RareCondition#HealthJourney#LifeChangingDiagnosis#MentalHealth#Vulnerability#SelfCompassion#PostTraumaticGrowth#MedicalMiracle#BBCSports#Inspiration#Cardiology#Surgery#Podcast#Healthcare#HeartHealth#MedicalBreakthrough#EmotionalJourney#SupportSystem#HealthcareHeroes#PatientStories#CardiologyCare#MedicalJourney#LifeLessons#MentalWellness#HealthAwareness#InspirationalTalk#LivingWithIllness#RareDiseaseAwareness#SharingIsCaring#MedicalSupport#BBCReporter#HeartDisease#PodcastInterview#HealthTalk#Empowerment#Wellbeing#HealthPodcast#Harryhill#weightloss#MounjaroCheck out our website at www.whostomanddick.com

Dr. Monty Pal and Dr. Matteo Lambertini discuss a compelling global study on the clinical behavior of breast cancer in young BRCA1 and BRCA2 carriers, the association of pre-diagnostic awareness of BRCA status with prognosis, and the importance of identifying healthy people who are at risk of carrying the BRCA1/2 pathogenic variants. TRANSCRIPT Dr. Monty Pal: Well, hello everyone, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist, professor, and vice chair of medical oncology at the City of Hope Comprehensive Cancer Center in Los Angeles. Now, when we think about genetic testing, whether for patients diagnosed with breast cancer or for other family members of them, it seems to be widely underutilized. Today, we're going to be discussing a recently published study in the Journal of Clinical Oncology that reported on the clinical behavior of breast cancer and specifically young BRCA1 and BRCA2 carriers, and the association of pre-diagnostic awareness of BRCA status with prognosis. I thought this was just a fascinating piece, and I honestly couldn't wait to have this conversation. It's a really compelling paper that highlights the importance of identifying healthy people who are at risk of carrying the BRCA1/2 pathogenic variants, and really the need for genetic counseling and testing to inform people about early detection that could lead to a better prognosis. I'm really delighted to welcome the study's lead author, Dr. Matteo Lambertini. He really needs no introduction. He's very well known in the breast cancer world for his amazing contributions to fertility in the context of breast cancer, to pregnancy in the context of breast cancer, and genetic testing. He's an associate professor at the University of Genova, and a breast cancer medical oncologist at the San Martino Polyclinic Hospital in Genova, Italy.  Dr. Lambertini, thank you so much for joining us today. Dr. Matteo Lambertini: Thank you very much, Dr. Pal. It's a great pleasure. Dr. Monty Pal: Oh, thanks. And just FYI, if you're listening in and you want to hear our disclosures, they're all listed at the transcript of this podcast.  So, I poured through this paper [Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status] yesterday, Dr. Lambertini, and first of all, congratulations on this study. This was a huge international multicenter effort, 4,752 patients. How did you pool all these patients with young breast cancer? Dr. Matteo Lambertini: Thanks a lot for the question. Yes, this was an effort made by several centers all over the world. The main idea behind the creation of this network that we have named as BRCA BCY Collaboration, was to get as many data as possible in a sort of niche patient population in the breast cancer field, meaning women diagnosed with breast cancer at the age of 40 years or younger, and all of them being BRCA carriers. We know that around, in the Western world, around 5% of breast cancer cases are being diagnosed under the age of 40 years, and among them around 10-15% are BRCA carriers. So, I would say it's a relatively rare patient population where we did not have a lot of evidence to support our choices in terms of counseling on treatment, prevention, and oncofertility as well. That was the idea behind the creation of this network that includes many centers. Dr. Monty Pal: Yeah. You know, what's so interesting about this is that you sort of draw this line between patients who have BRCA testing at the time of diagnosis and then BRCA testing earlier in their course and then leading to a diagnosis perhaps. And I think that's where really sort of the dichotomy in outcome sits. Can you maybe elaborate on this and tell us about timing of genetic testing in this study and what that meant ultimately in terms of prognosis? Dr. Matteo Lambertini: In this specific analysis from this large network, including almost 5,000 women with breast cancer diagnosed at the age of 40 years or younger and being a BRCA carrier, we looked specifically into the timing of genetic testing because this is a retrospective study and the criteria for inclusion are those that I have just mentioned, so diagnosis at a young age plus carrying germline BRCA pathogenic or likely pathogenic variant. In this analysis, we have looked into the time the patient has got the genetic testing and particular we focused on two populations: those that were diagnosed, knowing already to be a BRCA carrier, and those that got tested after being diagnosed with breast cancer. And the main findings from this analysis have been that knowing to be a BRCA carrier was associated with a lower stage at the time of diagnosis, meaning more T1 tumors, so a tumor less than 2 cm, more node-negative disease, and this translated into less aggressive treatment, so less often axillary dissection, less often use of chemotherapy and anthracycline-based chemotherapy. And even more importantly, we have seen a better overall survival for those patients that were diagnosed already knowing to be BRCA carriers as compared to those tested after breast cancer diagnosis. These results after adjusting for all the confounding, stage, treatment and so on, there was not significant anymore, meaning that it's not the timing of test per se that is probably leading to a better survival, but it is the fact that knowing to be a BRCA carrier would likely translate into having access to all the preventive measures that we have in this setting and this will translate into an overall survival benefit, so in terms of saving more lives in young BRCA carriers. Dr. Monty Pal: I think it's such an important point, and it's one that I think might sound implicit, right, but it needs to be proven, I think, through a study like this. You know, the fact that finding this early, identifying the mutation, doing enhanced screening, and so forth, is really going to lead to superior clinical outcomes. One of the things that I think many people puzzle over, including myself, is what to do? I personally occasionally will see BRCA altered patients in the context of prostate cancer. But that's a very different population of individuals, right? Typically older men. In young females with BRCA mutation, I guess there's a specific set of considerations around reproductive health. You'd already highlighted preventive strategies, but what sorts of things should we be talking about in the clinics once a patient's diagnosed and once perhaps their breast cancer diagnosis is established? Dr. Matteo Lambertini: Yes, exactly. Knowing to be a BRCA carrier has a lot of implications from prevention to treatment to survivorship issues including reproductive counseling. And this is important not only for the patient that has been diagnosed with breast cancer but also for all the family members that will get tested and maybe identify with this sort of genetic alteration before diagnosis of cancer. Why this is important is because we have access to very effective preventive measures, a few examples: MRI screening, which starts at a very young age and normally young women don't have an effective screening strategy outside the BRCA field. Also, primary preventive measures, for example, risk-reducing surgery. These women are known to have a high risk of breast cancer and high risk of ovarian cancer. So the guidelines are suggesting to undergo risk-reducing salpingo-oophorectomy at a young age, so 35 to 40 years in BRCA1 carrier, 40 to 45 years in BRCA2 carrier. And also risk-reducing mastectomy should be discussed because it is a very effective way to prevent the occurrence of breast cancer. And in some situations, including the setting that we are talking about, so young women with breast cancer, BRCA carrier, also risk-reducing mastectomy has shown to improve overall survival.  On the other side, once diagnosed with breast cancer, nowadays knowing to be or not a BRCA carrier can make a difference in terms of treatment. We have PARP inhibitors in the early setting, in the adjuvant setting as well as in the metastatic setting. And in terms of survivorship implication, one of the critical aspects for young women is the oncofertility care which is even more complicated when we talk about BRCA carriers that are women candidates for gynecological surgery at a very young age. So this sort of counseling is even more complicated. Dr. Monty Pal: One of the other things, and this is subtle in your paper and I hope you don't mind me bringing it up, is the difference between BRCA1 and BRCA2. It really got me thinking about that because there are differences in phenotype and manifestation. Do you mind just expanding on that a little bit for the audience because I think that's a really important reminder that you brought up in the discussion? Dr. Matteo Lambertini: The difference between BRCA1 and BRCA2 carriers has been known that there are different phenotypes of breast cancer that are more often diagnosed in these two different populations. Normally BRCA1 carriers have a higher likelihood to develop a triple negative breast cancer as compared to BRCA2 carriers, more likely to develop a hormone receptor-positive HER2-negative disease. In this study, again, a specific population of young women with breast cancer, we have seen the same findings, mostly triple negative disease in BRCA1 carrier, mostly luminal-like disease in BRCA2 carrier. But what's novel or interesting from this study is to look also at the age at the time of diagnosis of this disease. And particularly in BRCA1 carriers, we should be sort of more careful about diagnosis of breast cancer and also other primary tumors including ovarian cancer because the risk of developing these malignancies is higher even at a younger age as compared to BRCA2 carriers. And this has implications also in the primary and secondary prevention that we were talking about earlier. Dr. Monty Pal: Oh, interesting. I guess the fundamental question then from your paper becomes, how do we get at the right patients for screening for BRCA1 and BRCA2? And I realize our audience here is largely oncologists who are going to be listening to this podcast, oncology providers, MDs, nurses, etc. But maybe speak for a moment to the general practitioner. Are there things that, for instance, a general practitioner should be looking for to say, “Wait a minute, this patient's high risk, we should consider BRCA1, BRCA2 testing or germline screening”? Dr. Matteo Lambertini: Yes, it's a very important question for the breast cancer community. After the updated ASCO guideline, the counseling is way easier because right now the age cutoff goes up to 65 years, meaning that all the patients diagnosed with breast cancer below the age of 65 years should be tested these days. And then above the age of 65, there are different criteria like triple-negative disease or family history. From a general practitioner standpoint, it's of course a bit more difficult, but knowing particularly the family history of the person that they have in front will be crucial to know if there are cases of breast cancer diagnosed at a young age, maybe triple-negative cases, knowing cases of ovarian cancer in first-degree relatives or pancreatic cancer in first-degree relatives, and of course cases of prostate cancer as well. So, I would say probably mostly the family side will be important from a general practitioner perspective.  From an oncology one, the other point that I think is important to stress also based on the data that we have shown in this publication is that having a case of breast cancer known to carry a BRCA pathogenic or likely pathogenic variant. It means that all the people around this case should get tested and if found to be BRCA carrier and healthy carrier, these people should also undergo the primary and secondary prevention strategies because this is very critical also to improve their outcomes and try to avoid the developing of breast or ovarian cancer, but also in the case of diagnosis of this disease, a diagnosis at an earlier stage, as we have seen in this paper. Dr. Monty Pal: Brilliant. I'm going to diverge from our list of questions here and close by asking a question that I have at the top of my mind. You're very young. I know our podcast listeners can't see you, but you're very, very young. Dr. Matteo Lambertini: Thank you. Thank you for that. Not so young but yeah. Dr. Monty Pal: You have nearly 300 papers. Your H-index is 67. You've already made these seminal contributions, as I outlined it from the outset, regarding fertility, regarding use of GnRH analogs, regarding pregnancy and breast cancer. What are you studying now? What are you really excited about right now that you're doing that you think might potentially be practice changing? Give us a little teaser. Dr. Matteo Lambertini: Yeah. Thanks a lot, Dr. Pal. Receiving this compliment from you is fantastic. So, thanks a lot for that. From my side, in terms of my research, I've been interested in the field of breast cancer in young women since the start of my training. I've had very good mentors from Italy, from Europe, from the U.S. I'm still interested in this field, so I think we still have a lot to learn to try to improve the care of young women with breast cancer. For example, the oncofertility care, which is something I worked a lot over the past years. Now with all the new treatment options, there's a sort of new chapter of oncofertility counseling. So, what's the impact of immunotherapy? What's the impact of the new targeted agents?  More on the genetic aspects, now we know that there's not only BRCA1 or BRCA2. There are a lot of other different genes that may increase the risk of breast cancer and other malignancies. And also for these genes, we really don't have a lot of evidence to counsel women on prognosis, treatment, prevention strategy. So we need to learn way more for this special patient population that are quite rare, and so we really need a multicenter academic effort to try to give some evidence in this field. Dr. Monty Pal: Yeah. It's tough because these are rare circumstances, but, you know, I think that you've done really well to sort of define some collective experiences that I think really define therapy. I mean, I just remember when I was in training 25 years ago, just reading through textbooks where all the experience around breast cancer and pregnancy was really just very sort of anecdotal almost, you know? And so it's great to see that the state of the science has moved forward.  Well, gosh, I really enjoyed our conversation today. I think your study really reminds us how powerful genetic information is in terms of improving outcomes. And, you know, hopefully this will lead some individuals to perhaps test more broadly in appropriate settings. So, thank you so much, Matteo, for joining us today with your fantastic insights on the ASCO Daily News Podcast. Dr. Matteo Lambertini: Thank you very much, Dr. Pal. It's a real pleasure. Dr. Monty Pal: And thanks to our listeners too. You'll find a link to Dr. Lambertini's study in the transcript of this episode. Finally, if you value the insights that you heard today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks a ton. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:    Dr. Sumanta (Monty) Pal  @montypal  Dr. Matteo Lambertini @matteolambe   Follow ASCO on social media:     @ASCO on Twitter    ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Monty Pal:   Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview  Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical  Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis  Dr. Matteo Lambertini: Consulting or Advisory Role: Roche, Novartis, Lilly, AstraZeneca, Pfizer, MSD, Exact Sciences, Gilead Sciences, Seagen, Menarini, Nordic Pharma Speakers' Bureau: Takeda, Roche, Lilly, Novartis, Pfizer, Sandoz, Ipsen, Knight Therapeutics, Libbs, Daiichi Sankyo, Gilead Sciences, AstraZeneca, Menarini, AstraZeneca, Menarini Research Funding (Inst.): Gilead Sciences Travel, Accommodations, Expenses: Gilead Sciences, Daiichi Sankyo Europe GmbH, Roche

What if fear could become the framework for your strength?Chiropractor, business owner, and TEDx speaker Dr. Rubina Tahir joins Melissa Joy, CFP® for an inspiring and deeply personal conversation on navigating fear, health, and money with courage and clarity.Rubina shares her journey as a BRCA1 carrier, her shocking breast cancer diagnosis just weeks before delivering her TEDx talk, and how she built a practical framework—Honesty, Options, Decisions—to move from paralysis to empowerment. Along the way, she reveals why self-talk can be life-saving, how body autonomy shaped her medical choices, and what financial lessons she learned from facing the unexpected costs of cancer treatment.Together, Rubina and Melissa unpack the intersections of health and money: why knowing your deductible is essential, the role of disability insurance, and how emergency reserves protect you from both everyday curveballs and life-altering diagnoses.This episode is a reminder that while fear is inevitable, you do have power over your plan.

It's common knowledge that many diseases and conditions have some kind of genetic link. But that wasn't always the case. In 1990, long before the Human Genome Project tied so many health issues to differences in genetics, researchers identified a gene called BRCA1. It was the first gene linked to a hereditary form of any common cancer. People with certain variants of BRCA1 stood a higher risk of developing breast and ovarian cancer than those without those mutations.  Geneticist Mary-Claire King and her lab were the first to identify that gene. She joins Host Flora Lichtman to talk about her background, her research, and her approach to science.Guest: Dr. Mary-Claire King is an American Cancer Society Professor in the departments of Genome Sciences and Medicine at the University of Washington in Seattle.Transcripts for each episode are available within 1-3 days at sciencefriday.com. Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

Love the episode? Send us a text!In this special episode of Breast Cancer Conversations, host Laura Carfang speaks with Dr. Troso  about the evolving role of DNA testing in breast cancer care. Together, they break down the three main types of testing:Hereditary genetic testing: Identifying inherited mutations such as BRCA1, BRCA2, and PALB2 (among others) that increase cancer risk and influence prevention and treatment decisions.Somatic (tumor) testing: Analyzing mutations within the tumor itself—such as PIK3CA or ESR1 mutations—to guide targeted therapies and manage resistance in advanced disease.Circulating tumor DNA (ctDNA) testing: Also known as a liquid biopsy, this emerging tool uses blood tests to detect cancer DNA fragments. It holds promise for monitoring recurrence, guiding treatment earlier, and advancing clinical trials.Tune into this Special! 

Coraz więcej kobiet, które wykrywają u siebie szkodliwe geny BRCA1 i BRCA2 - decyduje się na tzw. operacje profilaktyczne. Chodzi o usuwanie piersi czy jajników. - To bardzo dobry rezultat tzw. efektu Angeliny Jolie - mówią nam lekarze z Lublina.

Send us a textOvarian cancer, the second most common gynecologic malignancy, can be cured 90-95% of the time when caught early. Speaking of Women's Health Podcast Host talks through the risk factors like family history, BRCA gene mutations, obesity, and personal reproductive factors that are essential for early detection and prevention.• Risk increases with age (over 50), family history, and BRCA gene mutations• BRCA1 carriers face 35-70% lifetime risk compared to less than 2% in general population• Pregnancy, breastfeeding, and hormonal contraceptives reduce risk by decreasing ovulation• Tubal ligation, especially salpingectomy, dramatically lowers ovarian cancer risk• Common symptoms include abdominal swelling, urinary changes, bloating, early satiety• Regular pelvic exams and prompt reporting of symptoms are crucial for early detection• Ashkenazi Jewish women have ten times higher rate of BRCA mutations• Avoid using talcum powder near genital area as it's been linked to increased risk• Consider genetic counseling if strong family history exists• Prophylactic removal of tubes/ovaries after age 40 may be recommended for high-risk womenPlease follow the Speaking of Women's Health podcast wherever you listen to podcasts. Remember Be Strong, Be Healthy, and Be in Charge!Support the show

Access the FREE Water Fasting Masterclass Now: https://www.katiedeming.com/the-healing-power-of-fasting/What lifestyle choices can reduce your risk before cancer develops? (Video ReRelease)Dr. Katie Deming sat down with Dr. Thomas Seyfried, professor of biology at Boston College and author of Cancer as a Metabolic Disease. Together, they explore how cancer cells depend on sugar and glutamine for fuel, why the mitochondria, not DNA mutations, may be at the heart of the disease, and what this understanding means for prevention and treatment.Key Highlights:Can dietary changes, fasting, and exercise support treatment once cancer is diagnosed? Why should patients and doctors pay attention to the Glucose Ketone Index (GKI) to measure how the body is fueling itself?What can you do today to reduce your risk of chronic illness?Dr. Seyfried explains the Warburg Effect, the role of dysfunctional mitochondria in cancer growth, and why standard treatments may sometimes work against us by feeding cancer's energy needs.Listen, learn the surprising story of how weight loss, not a new drug, led to dramatic tumor reduction in lab studies. Dr. Thomas Seyfried: https://www.bc.edu/bc-web/schools/morrissey/departments/biology/people/faculty-directory/thomas-seyfried.htmlAccess the FREE Water Fasting Masterclass Now: https://www.katiedeming.com/the-healing-power-of-fasting/ Transform your hydration with the system that delivers filtered, mineralized, and structured water all in one. Spring Aqua System: https://springaqua.info/drkatieMORE FROM KATIE DEMING M.D. Save your spot for the next LIVE fasting call here: https://www.katiedeming.com/the-healing-power-of-fasting/ Work with Dr. Katie: www.katiedeming.comEmail: INFO@KATIEDEMING.COM 6 Pillars of Healing Cancer Workshop Series - Click Here to Enroll Follow Dr. Katie Deming on Instagram: https://www.instagram.com/katiedemingmd/ Please Support the Show Share this episode with a friend or family member Give a Review on Spotify Give a Review on Apple Podcast DISCLAIMER: The Born to Heal Podcast is intended for informational purposes only and is not a substitute for seeking professional medical advice, diagnosis, or treatment. Individual medical histories are unique; therefore, this episode should not be used to diagnose, treat, cure, or prevent any disease without consulting your healthcare provider.

In this raw and real conversation, we sit down with a therapist and mom of three who opens up about what it was like to fall apart just when everything looked “fine.” She shares the unexpected crash of antenatal depression during her third pregnancy, the challenge of diagnosing herself when she's supposed to be the expert, and how she finally got the help she needed. We talk about receiving a BRCA+ diagnosis after her mother's cancer, deciding to undergo a preventive mastectomy (with a hysterectomy still to come), and grieving the loss of future fertility.  Julia also reflects on how her view of G-d has shifted from religious anxiety and bargaining to a more grounded kind of faith, and why posting honestly on social media became her lifeline. If you've ever felt pressure to “hold it together,” questioned your faith, or wondered how anyone survives the chaos of being human—this episode is for you.   Topics include: - What antenatal depression can actually look like (even when you're a therapist) - Getting a BRCA+ diagnosis and making hard decisions - Letting go of the fantasy of more children - Religious anxiety, fear, and finding balance - How humor and public storytelling became part of her healing - Control, or lack thereof—and learning to live with it Mentions: Sharsheret and Chai Lifeline More about Julia Makowsky:  Grew up in Los Angeles moved to New York for school where I was set up with my husband. I have a masters degree in social work and have been working in the field for over 13 years. I am a mom of 4 children and reside in the five towns. Recently I was diagnosed with BRCA1 where I have been navigating what is the best course of action for myself and my family. Connect with Julia:  - Follow her on Instagram   Connect with us: -Check out our Website -Follow us on Instagram and send us a message -Watch our TikToks -Follow us on Facebook -Watch us on YouTube -Connect with us on LinkedIn  

“Next-generation sequencing, or NGS, can be used to help us determine if the patient has specific biomarkers we can identify and use to target for treatment. Certain findings can tell us if a particular treatment might work for that patient, and we can see if there are any genetic variants we might have a biomarker targeted agent to use to treat them with,” ONS member Jackie Peterson, MSN, RN, OCN®, NE-BC, MBA, ambulatory nurse manager at the University of Chicago Medical Center in Illinois, told Lenise Taylor, MN, RN, AOCNS®, BMTCN®, oncology clinical specialist at ONS, during a conversation about prostate cancer and biomarker testing.  This podcast is sponsored by AstraZeneca and is not eligible for NCPD contact hours. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications.   Music Credit: “Fireflies and Stardust” by Kevin MacLeod    Licensed under Creative Commons by Attribution 3.0   Episode Notes This episode is not eligible for NCPD. ONS Podcast™ episodes: Episode 324: Pharmacology 101: LHRH Antagonists and Agonists Episode 321: Pharmacology 101: CYP17 Inhibitors Episode 180: Learn How Nurse Practitioners Use Biomarker Testing in Cancer Care ONS Voice articles: An Oncology Nurse's Guide to Cascade Testing Genetic Disorder Reference Sheet: BRCA1 and BRCA2 Hereditary Disorders Genetic Disorder Reference Sheet: Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) Germline and Somatic Variants: What Is the Difference? Help Patients Understand Genomic Variants of Unknown Significance Prostate Cancer Clinical Trials Don't Reflect Racial Diversity—And It's Getting Worse Over Time Prostate Cancer Disparities Disappear With Equal Access to Care Prostate Cancer Prevention, Screening, Treatment, and Survivorship Recommendations The Case of the Genomics-Guided Care for Prostate Cancer ONS book: Understanding Genomic and Hereditary Cancer Risk: A Handbook for Oncology Nurses ONS course: Genomic Foundations for Precision Oncology Clinical Journal of Oncology Nursing articles: Metastatic Prostate Cancer: An Update on Treatments and a Review of Patient Symptom Management Prostate Cancer: How Nurse Practicioners Can Aid in Disease Diagnosis and Management Oncology Nursing Forum article: Identification of Symptom Profiles in Prostate Cancer Survivors Other ONS Resources: Biomarker Database (refine by prostate cancer or specific biomarkers) Clinical tool/case study: Biomarker Testing in Prostate Cancer: The Role of the Oncology Nurse Genomics and Precision Oncology Learning Library Huddle Card: Genomic Biomarkers Infographic: Talking to Your Patient About a Germline Variant of Uncertain Significance (VUS) American Cancer Society - Genetic Testing and Counseling for Prostate Cancer Risk American Cancer Society - Prostate Cancer Clinicaltrials.gov National Cancer Institute - Prostate Cancer National Comprehensive Cancer Network ZERO Prostate Cancer To discuss the information in this episode with other oncology nurses, visit the ONS Communities.   To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library.  To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org.  Highlights From This Episode “Some of the risk factors for developing prostate cancer include age, race, family history, and certain genetic changes or variants. Prostate cancer has some hereditary components, but most prostate cancer occurs in men without any significant family history of it.” TS 1:31 “Key biomarkers include PSA and prostate cancer gene 3, which is PCA3, and prostate-specific membrane antigen, or PSMA. Other biomarkers that are important for us to test include BRCA1, BRCA2, and Lynch syndrome–associated genes, which are MLH1, MSH2, MSH6, PMS2, and EPCAM. Biomarkers can be collected via your blood, urine, saliva, or tissue samples, so these are different ways that we can test and look for biomarkers in our patients.” TS 3:24 “It does matter how advanced the disease is. Usually, for our castrate-sensitive patients, they respond better to androgen deprivation therapy because that really is slowing down the growth of the cancer by reducing the available testosterone that the cancer needs to grow. Whereas our patients that are more advanced and have castrate-resistant prostate cancer, that cancer will continue to grow despite having the lowered testosterone levels, so they might need additional layers of treatment to really get their cancer under control.” TS 7:50 “When I talk to [patients] about biomarker testing, I tell them it's another tool in our toolbox that we can use to help us determine if they might benefit from other therapy options now or in the future. I tell them that sometimes we'll get a report back with a variant of unknown significance, and basically that means that we don't really know whether or not this has an impact on their health or risk factors for the disease. That can sometimes be a little bit of a concern for these patients, so we just have to reassure them that we're continually doing research around biomarker testing. The science is always advancing, so if there's something that [researchers] find in the future, we'll make them aware of that.” TS 9:08 “One of the biggest topics I think about is the inequity that exists in biomarker testing and research, especially surrounding the African American population. When these tests were developed, that population really wasn't studied as much, so there's not a lot of good data yet to make a decision or impact on those patients and that population.” TS: 12:30

This episode discusses the Food and Drug Administration and National Institutes of Health Biomarker Working Group updates to the original 2018 BEST Resource in 2021, including the understanding and classification of biomarkers like BRCA1 and BRCA 2. This presentation highlights how these changes affect cancer risk diagnostics and provides a resource for evidence-based application of specific genetic testing in the pharmacist's clinical practice. CE for this episode expires two years after its original publication date.  The information presented during the podcast reflects solely the opinions of the presenter. The information and materials are not, and are not intended as, a comprehensive source of drug information on this topic. The contents of the podcast have not been reviewed by ASHP, and should neither be interpreted as the official policies of ASHP, nor an endorsement of any product(s), nor should they be considered as a substitute for the professional judgment of the pharmacist or physician.

Episode 2672 - BEST OF: Vinnie Tortorich welcomes Dr. Thomas Seyfried and they discuss metabolic dysfunction, glucose, glutamine, and cancer therapies. https://vinnietortorich.com/2025/07/glucose-glutamine-cancer-dr-thomas-seyfried-episode-2672 PLEASE SUPPORT OUR SPONSORS   YOU CAN WATCH THIS EPISODE ON YOUTUBE - Glucose, Glutamine, and Cancer Vinnie explains why he recommends listening to Dr. Thomas Seyfried. (2:00) Vinnie has been in remission and avoided chemo for 17 years by leading a ketogenic lifestyle. There are all kinds of side effects from chemotherapy, even though it can save people. There have been several theories of disease. (8:00) NCI states that cancer is a genetic disease of dysregulated cell growth, called the somatic mutation theory. Another theory suggests that damage to organelles can cause mutations in cells, or that mutations may have a mitochondrial metabolic origin. The treatment of cancer as a metabolic disease also allows people to participate in the management of their disorder. He explains the importance of oxygen and energy and how they affect the cells. (11:00) This is known as the mitochondrial metabolic theory of cancer. Dr. Seyfried explains some fascinating experiments and theories. (14:00) Once there is an agreement on the mitochondrial metabolic theory, treatment for cancers could be much less toxic and more manageable. (17:00) Metabolically treating cancer can help because even if there is recurrence, it can often be treated with fewer chemicals. (20:00) The idea is to reduce or eliminate the cancer through diet and medication that target the fermentation metabolism. Glutamine is an amino acid and has many uses in the body. (22:30) Dr. Seyfried explains the press-pulse therapeutic strategy. The Glucose Ketone Index What kind of diet and supplementation can help those who may have cancer? (27:30) The Glucose Ketone Index (GKI) calculator and its function are explained. How the GKI happens varies per person, but if you can keep the GKI measurement at 2.0 mmol or below, you can put pressure on the tumor cells. (29:00) Each person is their own experiment, but low-carb is beneficial as it keeps your ketones active. Vinnie asks Dr. Seyfried to explain ketone measurements and monitors. (32:30) They discuss genetics, such as the BRCA1 mutation. (36:00) They discuss the frustration of some doctors' approaches to other diseases. (40:00) Type 2 diabetes has replaced smoking as the number one risk factor for cancer! (43:15) They discuss the challenges of today's diet and lifestyle. (46:00) Low-cost and convenience foods are taking their toll on society's health. Type 2 diabetes is a diet and lifestyle issue. Give people the opportunity to make their own choices. Many doctors need to be re-educated, and people need to know all their options. (50:30) Processed food and glucose are a highly addictive force on the brain. (51:00) Dr. Seyfried is a professor who shares information about and is developing a protocol, which he hopes will be available soon. His website is: More News If you are interested in the NSNG® VIP group is currently closed for registration, but you can get on the wait list - Don't forget to check out Serena Scott Thomas on Days of Our Lives on the Peacock channel.  “Dirty Keto” is available on Amazon! You can purchase or rent it . Make sure you watch, rate, and review it! Eat Happy Italian, Anna's next cookbook, is available!  You can go to  You can order it from .  Anna's recipes are in her cookbooks, website, and Substack–they will spice up your day!  Don't forget you can invest in Anna's Eat Happy Kitchen through StartEngine.  Details are at Eat Happy Kitchen.    PURCHASE  DIRTY KETO (2024) The documentary launched in August 2024! Order it TODAY! This is Vinnie's fourth documentary in just over five years. Visit my new Documentaries HQ to find my films everywhere:  Then, please share my fact-based, health-focused documentary series with your friends and family. Additionally, the more views, the better it ranks, so please watch it again with a new friend! REVIEWS: Please submit your REVIEW after you watch my films. Your positive REVIEW does matter! PURCHASE BEYOND IMPOSSIBLE (2022) Visit my new Documentaries HQ to find my films everywhere:  REVIEWS: Please submit your REVIEW after you watch my films. Your positive REVIEW does matter! FAT: A DOCUMENTARY 2 (2021) Visit my new Documentaries HQ to find my films everywhere:  FAT: A DOCUMENTARY (2019) Visit my new Documentaries HQ to find my films everywhere: 

Featuring an interview with Ms Jennifer Filipi, including the following topics: Responsibilities of an oncology nurse and perspectives on the career (0:00) Case: A woman in her late 70s with BRCA1-mutated ovarian cancer (OC) (3:50) Case: A woman in her mid 40s, a mother of 3, with advanced OC (27:23) Case: A woman in her early 70s, a social worker, with platinum-refractory OC (40:02) NCPD information and select publications

Susan Wadia-Ells empowers women by revealing clear paths to prevent and reverse breast cancer naturally.New episodes of Welcome to Wellness released every Friday!Not listening on Spotify? Show notes at: https://www.ashleydeeley.com/w2w/bustingbreastcancerBuy Susan's book hereEpisode brought to you by: ⁠⁠⁠⁠⁠⁠ApolloNeuro⁠⁠⁠⁠⁠⁠Episode brought to you by:⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ VieLight⁠⁠⁠ - ⁠⁠⁠⁠⁠⁠⁠⁠⁠Code: DEELEY10Episode brought to you by:⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Dry Farm Wines⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Sneak Peek on top 5 steps to stop and prevent breast cancer:Avoid mammogramsStop taking hormonal birth control (but copper IUDs are great!)Lose excess fatStop holding onto highly stressful jobs/relationshipsFocus on mitochondrial health (Vitamin D3, reducing carbs, meditation)3:01: Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer by Dr. Thomas Seyfried13:13: Don't get tumors biopsied (seed & soil)... Episode with Dr. Katrina Lewis who had breast cancer twice (Episode 21)14:02: Mammogram controversy (be more like Switzerland!)18:29 Opt for Thermogram instead!23:00: Manage cancer metabolically (The Metabolic Approach to Cancer - Nasha Winters)23:39: Don't fear dense and lumpy breasts 29:23: Otto Warburg - Cancer can be starved - Cancer cells thrive on glucose30:37: Glutamine and DON (6-diazo-5-oxo-L-norleucine aka DON) - DON article 32:14: Anti-parasitic medicine32:45: Press-Pulse Theory35:49: It's time to manage your stress36:35: Should you cut off your breasts? BRCA1 and a BRCA2 and a P5340:44: Potatoes and corn vs. cabbage and Brussels sprouts44:30: Get off synthetic progestins (hormonal birth control)50:55: Use copper IUDs (as needed for birth control)Where to find Dr. Susan Wadia-Ells:WebsiteInstagramLinkedInWhere to find Ashley Deeley:⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Website⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Instagram⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Facebook⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠YouTube⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠hello@ashleydeeley.com

Episode 367: Pharmacology 101: PARP Inhibitors “We know that in cells that are proliferating very quickly, including cancer cells, single-strand DNA breaks are very common. When that happens, these breaks are often repaired by the PARP enzyme, and the cells can continue their replication process. If we block PARP, that repair cannot happen. So in blocking that, these single-strand breaks then lead to double-strand breaks, which ultimately is leading to cell apoptosis,” Danielle Roman, PharmD, BCOP, manager of clinical pharmacy services at the Allegheny Health Network Cancer Institute in Pittsburgh, PA, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about the PARP inhibitor drug class. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by June 13, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: Learners will report an increase in knowledge related to the use of PARP inhibitors in cancer care. Episode Notes  Complete this evaluation for free NCPD.  ONS Podcast™ episodes: Pharmacology 101 series Episode 330: Stay Up to Date on Safe Handling of Hazardous Drugs Episode 232: Managing Fatigue During PARP Inhibitor Maintenance Therapy Episode 227: Biomarker Testing, PARP Inhibitors, and Oral Adherence During Ovarian Cancer Maintenance Therapy ONS Voice articles: PARP Inhibitors and Ovarian Cancer Genomics May Trick PARP Inhibitors to Treat More Cancers Oncology Drug Reference Sheet: Niraparib ONS books: Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (second edition) Clinical Guide to Antineoplastic Therapy: A Chemotherapy Handbook (fourth edition) Safe Handling of Hazardous Drugs (fourth edition) ONS courses: Safe Handling Basics Clinical Journal of Oncology Nursing articles: PARP Inhibition: Genomics-Informed Care for Patients With Malignancies Driven by BRCA1/BRCA2 Pathogenic Variants Talazoparib Plus Enzalutamide in Patients With HRR-Deficient mCRPC: Practical Implementation Steps for Oncology Nurses and Advanced Practice Providers Oncology Nursing Forum article: Familiarity and Perceptions of Ovarian Cancer Biomarker Testing and Targeted Therapy: A Survey of Oncology Nurses in the United States Oral Anticancer Medication Care Compass: Resources for Interprofessional Navigation ONS Biomarker Database ONS Oral Anticancer Medication Learning Library ONS Oral Anticancer Medication Toolkit Oral Chemotherapy Education Sheets To discuss the information in this episode with other oncology nurses, visit the ONS Communities. To find resources for creating an ONS Podcast Club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode “The big toxicities here to watch for are primarily hematologic toxicities. It is one of those targeted therapies that does affect blood cell counts. So I'd say the blood cell count that is most commonly affected here is the hemoglobin. So, anemia very frequent complication that we see, probably a little bit more with olaparib compared with other drugs, but we see it as a class side effect. And we can also see neutropenia and thrombocytopenia with these agents, probably a little bit more with niraparib versus the others, but again, you can see it across all of these drugs.” TS 8:16 “We mentioned that rare risk of MDS and AML. This isn't a particularly scary thing if you talk to patients about it. Because of the rarity that we see this, it isn't something that we need to overemphasize, but I think careful monitoring of blood counts in is stressing the importance of that and early intervention here is very important.” TS 16:55 “This is a collaborative effort. And because of the home administration here, these patients do need to be followed very closely. So we are not laying eyes on them usually with the frequency that we do when we have patients actually coming into our infusion centers for treatments—so making sure that there is a plan for regular follow-up with these patients to ensure that they're getting that lab work done, that that's being looked at closely, that we're adjusting the dose if we need to based on that lab work, that we are managing the patient's fatigue. Again, that potentially dose reductions may be needed if patients are having that extreme fatigue.” TS 19:34 “I think one of those [misconceptions] could be that they're only effective in patients that have that BRCA1/2 mutation. And again, remember here that there is some data in particular disease states that we can use them and that they work in the absence of those mutations.” TS 25:12