Podcasts about BRCA2

Ashley Dedmon is a women's health advocate. This week, she shares her compelling story to ensuring she never experiences breast cancer. As a BRCA2 positive patient and having lost her mother to breast cancer, Ashley made the difficult decision to have a double mastectomy. She also speaks about the impact of her father's cancer diagnosis and how it strengthened her resolve. During this episode, you'll hear her story of survival and how her decision helped her to take control of her life. And you'll learn how Ashley's helping women make informed choices. Support The Rose HERE. Subscribe to Let’s Talk About Your Breasts on Apple Podcasts, Spotify, iHeart, and wherever you get your podcasts.See omnystudio.com/listener for privacy information.

Broadcast from KSQD, Santa Cruz on 8-20-2026: An emailer asks about amlexanox for mast cell activation syndrome (MCAS). Dr. Dawn first walks through MCAS diagnostic criteria—requiring symptoms across at least two of four categories (skin, low blood pressure, abdominal, respiratory), with serum tryptase testing performed both during and after a flare. She grades amlexanox as a C: originally FDA-approved only as a topical paste for canker sores, later approved in Japan as an asthma treatment, but never validated for MCAS and pushed largely by a single compounding pharmacy and its influencer clones. She recommends conventional agents first—antihistamines, montelukast, cromolyn, quercetin, aspirin for flushing, and Xolair anti-IgE antibodies for severe cases—plus microcrystalline cellulose as the safest capsule filler if compounding of amellanox is pursued. Most ovarian cancers—including nearly all fatal cases—actually originate in the fimbriae of the fallopian tubes rather than the ovaries themselves. Opportunistic salpingectomy tacks a five-minute fallopian tube removal onto any abdominal surgery (tubal ligation, hernia repair, gallbladder, appendectomy), potentially reducing lifetime ovarian cancer risk by 65% -80% based on epidemiological data from Swedish, Canadian, and Danish registry studies. Dr. Dawn recommends particular consideration for non-childbearing women with BRCA1/2 or family history of breast or ovarian cancer. Deep brain stimulator devices manufactured after 2020 (about 40,000 U.S. patients) contain adaptive-DBS capability that can be activated via firmware upgrade without additional surgery. Rather than delivering constant stimulation like older devices, adaptive DBS reads beta oscillations (13-30 Hz motor-control brainwaves) in the basal ganglia and modulates output in real time—reducing stimulation as L-DOPA peaks from drugs and increasing it as medication wears off, smoothing the swings between agitation and freezing. Sleep improvement has emerged as a notable secondary benefit, potentially slowing disease progression. The technology is also being investigated for dystonia, essential tremor, OCD, and Tourette's syndrome. Chinese company StarMed is developing brain-computer interfaces closely resembling Neuralink designs, benefiting from aggressive government funding, large patient populations, and reduced tort liability. One trial uses an eight-probe device placed atop the dura mater (avoiding brain penetration) connected to a pneumatic glove that has restored eating and drinking function in about twenty paralyzed patients over twenty months. A more invasive Shanghai trial implanted 256 probes on the neural cortex of a woman with epilepsy who could operate social media and control a wheelchair within two weeks; a related U.S. system using 65 hair-thin sensors enabled speech with just ten-millisecond delay. An emailer describes recurring two-week viral illnesses (sore throat, swollen glands, congestion, cough, body aches) recurring every 4-6 weeks. Dr. Dawn frames the question as either impaired immunity or changed exposure. She recommends starting with a CBC to rule out blood dyscrasias like leukemia, checking urine mycotoxins for mold exposure, then examining behavioral changes—new job, handling cash before eating, and the well-documented protective effect of masking in public that dramatically reduced cold rates during COVID. Dr. Dawn covers three health policy items. The good: new USDA dietary guidelines flip the food pyramid, putting protein, dairy, healthy fats, vegetables, and fruits at the top, with whole grains reduced to a small band, and it's recommendation 1.2 g/kg protein daily. The bad: an executive order attempting to reduce childhood vaccines from 18 to 11 and separate MMR into individual components—impossible since no U.S. manufacturer makes the individual antigens, and misguided since infant hepatitis B vaccination prevents mother-to-child liver cancer transmission. The ugly: a 26-year-old heart transplant recipient whose insurer initially dropped coverage of her generic anti-rejection drug, then "ghost approved" it at $1,000 for 90 days versus the previous $180. Mark Cuban's Cost Plus Pharmacy now supplies her the same medication for $300 (cost plus 15% profit plus 5% handling), highlighting the massive markups embedded in the standard pharmacy chain. For a time before that, the mother of the heart donor stepped up and paid for the recipients anti-rejection drugs to keep her son's heart beating.

Singer and TV presenter Michelle Heaton's story is about more than addiction. It's about identity, loss, and finding your way back to yourself.In this episode, Michelle shares how a BRCA2 diagnosis, surgical menopause, and addiction became deeply intertwined, and how recovery helped her reconnect with the person she thought she'd lost.Together, we explore shame, healing, and why recovery is never just about one person.This episode covers the following themes: Surgical Menopause & Identity, Active Addiction, Shame & Isolation, Recovery, and Supporting Loved Ones.Need Support?Samaritans: Call 116 123 or visit samaritans.orgNarcotics Anonymous: na.orgAlcoholics Anonymous: alcoholics-anonymous.org.ukMental Health Mates: mentalhealthmates.co.ukShout: https: giveusashout.orgIAPT: https://www.england.nhs.uk/mental-health/adults/nhs-talking-therapies/Catch Michelle Heaton as Snow White in Snow White & The Seven Dwarfs at Whitley Bay Pantomime this Christmas. Tickets available here: https://www.axs.com/uk/series/30228/snow-white-the-seven-dwarves-whitley-bay-playhouse-tickets?skin=playhouseRandox

Send us Fan MailA colonoscopy that comes back normal can feel like relief, until your body keeps proving something is wrong. We sit down with Dr. Matthew J. Simpson, a family medicine physician in North Carolina, to unpack how he lived with Crohn's disease symptoms for years without a clear diagnosis, and why a perianal fistula finally forced the medical system to see the full picture. If you've ever been told your labs look fine while you're dealing with bleeding, urgency, fatigue, or weight loss, you'll hear your reality reflected back with empathy and precision. We talk about what it's like to chase answers while living outside a major medical hub: limited local gastroenterology options, slow referral pipelines, insurance approvals, and fragmented care between GI, colorectal surgery, and imaging. Matthew walks us through the flex sig, MRI findings, and the moment he realized he needed an IBD specialty clinic and an academic medical center approach. His story is a clear reminder that “not unreasonable” care can still be the wrong pace when your health is sliding. Then we get practical. Matthew explains perianal fistulas in plain language, what a fistulotomy does (and does not do), and why healing often requires treating the underlying Crohn's inflammation. We also dig into shared decision making for Crohn's medications, including how he weighed biologic options, risk communication, and the added complexity of carrying a BRCA2 gene mutation. Along the way, we challenge overreliance on single tests like fecal calprotectin and zoom out to the bigger point: algorithms are helpful, but they are not your lived experience. If this conversation helps you feel less alone, please subscribe, share it with someone navigating IBD, and leave a review so more people can find the show.Links: What is anorectal manometry?- Cleveland ClinicFistulotomy- Cleveland ClinicLet's get social!!Follow us on Instagram!Follow us on Facebook!Follow us on Twitter!

O episódio 45 do EVA CAST, o podcast do Grupo Brasileiro de Tumores Ginecológicos, discute o papel cada vez mais estratégico da patologia e dos biomarcadores na tomada de decisão no câncer de ovário. Muito além da confirmação do diagnóstico, a patologia passou a integrar informações histológicas, imunohistoquímicas e moleculares que ajudam a definir prognóstico, selecionar terapias-alvo e orientar uma abordagem cada vez mais personalizada para as pacientes. Participam da conversa Karla Kabach, médica patologista do Hospital Israelita Albert Einstein, com foco em tumores ginecológicos, e professora adjunta do Departamento de Patologia da Escola Paulista de Medicina (Unifesp); Louise De Brot, médica patologista e head de Patologia do A.C.Camargo Cancer Center e membro do Comitê de Ética do Grupo EVA; e Márcia Graudenz, professora titular do Departamento de Patologia da Universidade Federal do Rio Grande do Sul e chefe do Laboratório de Patologia e Biologia Molecular do Hospital Moinhos de Vento, em Porto Alegre. Ao longo do episódio, as especialistas explicam como a caracterização molecular do câncer de ovário vem transformando a prática clínica e ampliando as possibilidades da medicina de precisão. Entre os temas abordados estão os diferentes subtipos histológicos do câncer de ovário, a importância da imunohistoquímica e do sequenciamento genético na classificação tumoral, o papel da deficiência de recombinação homóloga (HRD) e das mutações em BRCA1 e BRCA2, além de outros biomarcadores que já influenciam ou poderão influenciar a escolha das terapias nos próximos anos. As convidadas também discutem como patologistas e oncologistas trabalham de forma integrada para individualizar o tratamento e aumentar as chances de benefício para cada paciente. O episódio aborda ainda os desafios para ampliar o acesso aos testes moleculares no Brasil, a necessidade de padronização dos exames, a importância do aconselhamento genético e o impacto que essas informações têm não apenas na escolha do tratamento, mas também na identificação de síndromes hereditárias e no cuidado dos familiares. Na reta final da conversa, as especialistas apresentam as principais perspectivas para o futuro da patologia em ginecologia oncológica. Entre os temas estão a biópsia líquida, o monitoramento molecular longitudinal, a inteligência artificial, a patologia digital, além de novas linhas de pesquisa envolvendo microbioma, metaboloma e outros biomarcadores capazes de aprimorar ainda mais a medicina de precisão no câncer de ovário. Como mensagem final, as convidadas reforçam que a patologia deixou de ser apenas uma especialidade diagnóstica para assumir um papel central na oncologia contemporânea. Integrar conhecimentos morfológicos, moleculares e genômicos, ampliar o acesso às tecnologias e fortalecer a formação de novos especialistas são passos fundamentais para oferecer tratamentos cada vez mais precisos e melhorar o prognóstico das mulheres com câncer de ovário.

In this episode of the Breast Cancer Now podcast, we speak to Tamara about her diagnosis of triple negative breast cancer, cancer in Black communities, and the impact of discovering she carries the BRCA2 gene mutation.Tamara opens up about the emotional weight of having to explain her cancer and her behaviour to the people around her. She also explores the stigma and mistrust that surrounds cancer in Black communities, and why culturally sensitive education is the key to improving outcomes.The conversation explores the feeling of dismissal Black women face in healthcare settings, and the incredible support Tamara experienced when she found Black Women Rising.Find support at Breast Cancer NowMore info about Younger Women Together coursesFind support at Black Women RisingFind support at UK Charity for Triple Negative Breast CancerFrom Me To You - Supporting Black Cancer Communities.You can also watch this episode on YouTube.Key Topics:2:50 Life before diagnosis5:36 Mara's breast cancer diagnosis11:08 Conversations about the BRCA gene mutation13:52 Understanding triple negative breast cancer20:37 Black women experiencing dismissal in healthcare22:48 What needs to be done to help improve healthcare for Black women?24:13 How Mara's diagnosis was received by her family and her community25:32 Mental health support at the point of cancer diagnosis28:58 Christian beliefs and breast cancer32:02 Difficulty talking with other people about your cancer diagnosis39:46 The power of the breast cancer community41:20 Body image after surgery for breast cancer44:01 Improving education in black Caribbean and black African communities51:18 Mara's work with Black Women Rising

For many families, cancer doesn't affect just one person. It can shape generations.⁣ When a parent is diagnosed with cancer, children often carry more than memories. They may inherit questions, uncertainty, increased risk, and life-changing decisions of their own.⁣ ⁣ In this conversation, Ashley Dedmon shares her experience of losing her mother to metastatic breast cancer, learning she carried the BRCA2 gene mutation, and ultimately making the decision to undergo a preventive mastectomy.⁣ ⁣ Together, we discuss hereditary cancer risk, genetic testing, prevention, family planning, and how understanding your family history can empower you to make informed decisions for yourself and future generations.⁣ Ashley also shares how her personal experience inspired her work as a national public health leader, patient advocate, and children's book author helping families navigate conversations about cancer and family health history.⁣ ⁣ Most importantly, this episode is a reminder that while we cannot change our family history, we can make informed decisions that help shape what comes next.⁣ ⁣ Resources Mentioned in This Episode:⁣ ⁣ To learn more about Ashley Dedmon's work, follow her on Instagram at @PinkLegacy5050 and explore her children's books, The Big Discovery and The Big Family Trip, which help families navigate conversations about cancer and family health history.⁣ ⁣ For additional education and support, visit Living Beyond Breast Cancer (LBBC) or follow @LivingBeyondBC on Instagram.⁣ ⁣ The information shared on Dear Cancer, I'm Beautiful is for educational and informational purposes only and is not intended as medical advice. Always consult your physician or qualified healthcare provider regarding your individual medical care and treatment decisions. The views and opinions expressed by guests are their own and do not necessarily reflect those of Cancer Fashionista.

Welcome to the Hot Topics podcast from NB Medical with Dr Neal Tucker. In this episode, we have three new pieces of research and a special interview later on discussing the recommendations of the National Screening Committee on prostate cancer screening in the UK.First up for research: nasal sprays versus the common cold. The BJGP reports on longer-term findings through this simple intervention. Can it help this age-old problem?Second, new kid on the block, orforglipron - could it replace SGLT2 inhibitors for management of type 2 diabetes?Third, home-based hypnotherapy. Can it help children struggling with functional abdominal pain or IBS? We have a RCT to tell us. Finally, our interview with Dr Liz Bancroft, consultant nurse in oncogentics research, and Natalia Norori, interim Head of Data and Evidence at Prostate Cancer UK join us to discuss the new recommendations from the National Screening Programme with targeted screening of men with BRCA2, why they made this recommendation and how this affects us in general practice, plus what we need to know for our patients about the government-backed trial, TRANSFORM.ReferencesProstate Cancer UK Information on NSC decisionProstate Cancer UK Health Professional NSC FAQsNational Screening Committee report on prostate cancer screeningBJGP Nasal sprays for the common coldLancet Nasal Sprays original paperLancet Orforglipron vs dapagliflozin and T2DMBJGP Hypnotherapy in children for abdo painNational Screening Committee report on prostate cancer screeningwww.nbmedical.com/podcast

With multiple clinical trials evaluating PARP inhibitor combinations, how do clinicians determine the best approach for advanced prostate cancer? In this episode of BackTable Urology, Dr. Alan Tan is joined by Dr. Rana McKay and Dr. Emmanuel Antonarakis to discuss how evolving evidence, patient selection, timing, toxicity, and genetic testing are shaping the use of PARP inhibitor combinations in clinical practice. --- Get the BackTable apphttps://www.backtable.com/app --- This podcast is supported by an educational grant from Pfizer. --- Timestamps 00:00 - Introduction02:51 - PARPi Basics14:12 - Major Study Differences19:00 - Timing and Selection of PARPi Combinations26:39 - Case: Somatic BRCA2 loss and mHSPC35:51 - Case Continued: BRCA2 Reversion39:57 - BRCAAway Study42:59 - Takeaways from the 2026 APCCC --- More about this episode The conversation reviews lessons learned from major clinical trials, including PROpel, MAGNITUDE, TALAPRO-2, and AMPLITUDE, and addresses how these studies inform real-world treatment choices. The doctors dig into case examples, such as BRCA2 loss and reversion, and highlight practical strategies for using germline and somatic testing to personalize care. Key insights from the 2026 Advanced Prostate Cancer Consensus Conference are also shared, emphasizing the importance of precision medicine in this rapidly evolving field. --- Resources Study on Olaparib Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer (PROpel) https://clinicaltrials.gov/study/NCT03732820 A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer (MAGNITUDE) https://clinicaltrials.gov/study/NCT03748641?tab=study Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC (TALAPRO-2) https://clinicaltrials.gov/study/NCT03395197 A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) (AMPLITUDE) https://clinicaltrials.gov/study/NCT04497844 BRCAAway: A randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) bearing homologous recombination-repair mutations (HRRm) https://pubmed.ncbi.nlm.nih.gov/39115414/ --- BackTable Urology is the go-to podcast for urologists, urologic oncologists, and urogynecologists. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

In this episode of the Breast Cancer Now podcast, we explore the role of genetics in cancer risk, including BRCA1 and BRCA2 gene mutations, specifically in Jewish populations.Naomi shares her powerful story after discovering she carries the BRCA2 gene mutation following the loss of her mum to ovarian cancer. With an 80% lifetime risk of breast cancer, She faced life-changing decisions, and opted for risk-reducing surgery.Naomi speaks about what it's like to live with that knowledge, how it shaped her choices, and why taking preventative action gave her a sense of control. She also shares the impact of her gene mutation on her children, and how they've dealt with it as a family.We're also joined by Josh from Jnetics, a Jewish genetic disorders charity, who explains the science behind BRCA gene mutations, why they increase cancer risk, and why they are more common in people with Jewish ancestry. He also outlines how testing works, who may be eligible, and what support is available.Breast Cancer NowWebsite: https://breastcancernow.orgFree helpline: 0808 800 6000Jewish BRCA Testing Programme (NHS England)Register interest: https://www.jewishbrca.orgHelpline: 020 3437 6001Jneticshttps://www.jnetics.orgChai Cancer Carehttps://www.chaicancercare.orgYou can also watch this episode on YouTube.Key topics:1:29 Getting to know Naomi and Josh4:00 A history of cancer in Naomi's family7:50 Naomi is tested for the BRCA gene mutation9:35 What is a genetic mutation or gault?12:20 Why is the BRCA gene mutation more common in Jewish populations?17:24 What is BRCA, how does it work, and why does it break?20:38 Naomi's increased risk of cancer23:32 Naomi makes the choice to have risk-reducing surgery27:01 The psychological impact of risk-reducing surgery28:34 Support for carriers of gene mutations31:53 How to get tested for BRCA gene mutations35:52 Coping with the fear of having genetic testing37:52 Naomi decides how to deal with her daughters potentially being BRCA carriers39:47 Dealing with feelings of guilt passing on a genetic mutation to a child41:15 Preventing gene mutations with IVF42:20 Research into fixing faulty genes44:06 Cultural barriers to genetic testing within Jewish populations46:51 Hope for the future of genetic mutations50:08 More information for people with Jewish heritageBRCA gene, BRCA2, breast cancer risk, genetic testing UK, hereditary cancer, ovarian cancer risk, mastectomy prevention, cancer genetics, Jewish BRCA, NHS genetic testing, breast cancer awareness UK

Can you really treat prostate cancer effectively without knowing the genetics? In this episode of BackTable Urology, Dr. Evan Yu and Dr. Tanya Dorff join host Dr. Alan Tan to discuss why genetic testing is essential in personalized prostate cancer care. They discuss when and how to perform germline and somatic testing, address common barriers, and share best practices for counseling patients. --- Get the BackTable apphttps://www.backtable.com/app --- This podcast is supported by an educational grant from Pfizer. --- Timestamps 00:00 - Introduction02:18 - Who Gets Somatic Testing?06:43 - Patient Barriers to Testing09:00 - Genetic Testing Workflow12:28 - Treating BRCA2 Alterations24:18 - Monitoring Progression: ctDNA vs. PSA vs. Imaging29:32 - Treating mCRPC with ATM Mutations34:39 - CDK12 Classification 37:43 - Closing Takeaways --- More about this episode The doctors explore how BRCA2 and other DNA repair alterations can directly shape treatment decisions, focusing on the roles of PARP inhibitors and platinum therapy in advanced cases. The discussion highlights why both germline and somatic testing are critical for identifying actionable mutations and discuss the nuances of interpreting test results, including current limitations and emerging biomarkers. They also examine challenges such as insurance coverage, patient misconceptions, and workflow integration, as well as the movement toward truly personalized, biology-driven approaches in prostate cancer care. --- Resources Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial:https://pmc.ncbi.nlm.nih.gov/articles/PMC12705445/ Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study:https://www.annalsofoncology.org/article/S0923-7534(25)04936-1/fulltext Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer:https://www.nejm.org/doi/full/10.1056/NEJMoa1903307 ARCHES 5-year Survival with Enzalutamide Plus Androgen-deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer Patientshttps://www.sciencedirect.com/science/article/pii/S0302283825048766 First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer:https://www.nejm.org/doi/abs/10.1056/NEJMoa2502929 PROMISE Registry:https://www.prostatecancerpromise.org/ Talazoparib plus enzalutamide in men with HRR-deficient metastatic castration-resistant prostate cancer: final overall survival results from the randomised, placebo-controlled, phase 3 TALAPRO-2 trial:https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00683-X/abstract --- BackTable Urology is the go-to podcast for urologists, urologic oncologists, and urogynecologists. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

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.

O episódio 43 do EVA CAST, o podcast do Grupo Brasileiro de Tumores Ginecológicos, aborda como a oncologia de precisão vem transformando, na prática, o tratamento do câncer de ovário. Em um cenário marcado pelo avanço da biologia molecular, o episódio discute como testes genéticos, biomarcadores, inibidores de PARP, imunoterapia e novas terapias-alvo passaram a redefinir estratégias terapêuticas e ampliar as possibilidades de cuidado personalizado para as pacientes. Participam da conversa Mariana Scaranti, oncologista clínica da Rede Américas e diretora de pesquisa do EVA; Noele Gomes, oncologista clínica do Hospital São Domingos, no Maranhão; e Andreia Cristina de Melo, oncologista clínica da Oncologia Américas e chefe da Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico do INCA. Ao longo do episódio, as especialistas discutem como a caracterização molecular dos tumores ovarianos mudou a prática clínica nos últimos anos e passou a orientar desde a escolha da manutenção até o sequenciamento terapêutico em doença recorrente. Entre os principais pontos abordados estão os biomarcadores que atualmente impactam a tomada de decisão terapêutica, como BRCA1 e BRCA2, deficiência de recombinação homóloga (HRD), PD-L1, HER2, receptor de folato alfa e deficiência de mismatch repair. O episódio também detalha o momento ideal para realização de testes genéticos e moleculares e explica como essas informações passaram a influenciar diretamente a seleção de terapias-alvo e o manejo individualizado das pacientes. A conversa explora ainda os avanços recentes em diferentes subtipos da doença, incluindo o carcinoma seroso de baixo grau, com destaque para estudos envolvendo hormonioterapia, inibidores de CDK4/6 e drogas direcionadas à via MAP-quinase. Também são discutidos os resultados mais recentes apresentados em congressos internacionais, como estudos com anticorpos droga-conjugados, imunoterapia e novas estratégias para pacientes com doença resistente à platina. Outro eixo importante do episódio é o impacto dos inibidores de PARP na história natural do câncer de ovário, especialmente em pacientes com mutação em BRCA ou HRD positivo, além da discussão sobre como a doença começa a caminhar para um modelo de cuidado mais próximo ao de uma condição crônica, com múltiplas linhas de tratamento personalizadas ao longo do tempo. As especialistas também analisam os desafios de acesso no Brasil e em outros países de baixa e média renda, incluindo desigualdades entre sistemas público e privado e dificuldades na incorporação de testes e terapias inovadoras. Como mensagem final, as convidadas reforçam que a oncologia de precisão já deixou de ser uma perspectiva futura e passou a fazer parte do presente do tratamento do câncer de ovário, embora ainda existam barreiras importantes para garantir acesso amplo e equitativo às pacientes.

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

Menopause – it may be the most unwanted time in a woman's life. It arrives with a vengeance, forcing all kinds of emotional, hormonal and bodily changes onto women as they approach their 50s. But for women going through breast cancer treatment, it can arrive even earlier and be even more unwanted. The good news is no one has to suffer in silence. Today's guests are Dr. Makeba Williams, the incoming president of The Menopause Society, and Claudia McConnell, a breast cancer survivor who was forced into menopause during breast cancer treatment at age 37. Key takeaways Breast cancer treatment can trigger sudden and emotionally overwhelming early menopause Menopause symptoms after cancer treatment are real, serious, and treatable. Mental health support is a critical part of breast cancer survivorship care. Open conversations help reduce stigma and empower women to seek support. Chapters 00:00 Introduction to breast cancer and menopause realities 04:29 Claudia's breast cancer diagnosis and sudden menopause at 37 15:42 Why survivors shouldn't suffer through menopause symptoms alone 19:20 New menopause treatments and advances for breast cancer survivors 21:07 Sleep disruption, insomnia, and menopause management strategies 24:07 Estrogen creams, vaginal health, and treatment decision-making 30:19 BRCA2, talking to children about cancer risk, and family support 39:05 Final advice for women navigating menopause after breast cancer Learn more at realpink.komen.org and komen.org breastcancer #menopause #survivorship #womenshealth #cancersupport #realpink Real Pink, by Susan G. Komen, shares real stories and expert insights to support people navigating breast cancer, from diagnosis through survivorship.

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

Welcome to the Oncology Brothers podcast! In this episode, we discussed the current treatment landscape for prostate cancer, featuring special guest Dr. Scott Tagawa, a GU Medical Oncologist from Weill Cornell Medicine. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Follow us on social media: X/Twitter: https://twitter.com/oncbrothers Instagram: https://www.instagram.com/oncbrothers Website: https://oncbrothers.com/ Join us as we explored: The current standard of care for localized prostate cancer, including active surveillance, surgery, and radiation. The significance of ADT and abiraterone in high-risk disease, supported by the STAMPEDE trial. The role of PSMA PET/CT in staging and how it impacts treatment decisions. Treatment options for castration-sensitive and castration-resistant prostate cancer, including the use of ARPi and chemotherapy. The importance of germline and somatic testing, especially with the recent approval of Niraparib for BRCA2-positive disease. Insights on managing side effects and the nuances of patient-centered care in oncology. Whether you're a healthcare professional or someone interested in the latest advancements in cancer treatment, this episode is packed with valuable information to help you stay informed. Don't forget to like, subscribe, and hit the notification bell for more episodes from the Oncology Brothers! #ProstateCancer, #ADT, #PSMA, #PARPinhibitor, #OncologyBrothers

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

Elizabeth Klug is a mother, wife, and realtor whose story is shaped by the unimaginable—and the love that remains. She and her husband are both BRCA2 gene carriers, and they lost two of their four children to Fanconi anemia, a rare and fatal genetic condition. In this raw and powerful conversation, Elizabeth shares what it's like to parent through grief, how she and her husband survived the strain of repeated loss, and why she still proudly says she's a mom of four.Heather and Elizabeth talk about marriage, advocacy, and the pressure to stay strong when your world has been shattered. They explore the complex emotions of guilt and anger, the burden of genetic knowledge, and how Elizabeth's living children continue to bring meaning, connection, and light into her life. This conversation is deeply honest, heartbreaking, and full of hard-earned wisdom from a woman learning to live alongside grief.Resources & Ways to ConnectLearn more about Fanconi anemia:https://www.fanconi.org/Jake's Help from Heaven Website: http://jakeshelpfromheaven.org/Jake's Help from Heaven Instagram: https://www.instagram.com/jakeshelpJake's Help from Heaven Facebook: https://www.facebook.com/jakeshelpAPOY Instagram: https://www.instagram.com/aplaceofyespodcastHeather's Instagram: https://www.instagram.com/heathersstraughterOur YouTube Channel: https://www.youtube.com/@aplaceofyespodcast

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: 

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving deep into the latest breakthroughs, regulatory updates, and industry trends shaping the future of healthcare.Let's start with Johnson & Johnson's recent achievement in precision oncology. They've secured a second FDA approval for Akeega, a combination therapy that merges J&J's Zytiga with GSK's Zejula. This innovative approach targets BRCA2-mutated metastatic castration-sensitive prostate cancer, marking a significant advancement in personalized medicine. This approval not only highlights the progress in tailored treatment strategies but also sets a new benchmark for therapeutic innovation in this particular cancer subset.Moving on to cardiovascular health, Cincinnati's LIB Therapeutics has introduced Lerochol, a third-generation PCSK9 inhibitor designed to lower cholesterol. Unlike its predecessors, Lerochol offers simplified administration, potentially improving patient adherence and outcomes. This approval is part of a broader effort to refine lipid-lowering therapies and better address cardiovascular diseases.In a groundbreaking development for heart rhythm disorders, Milestone Pharmaceuticals has received FDA approval for Cardamyst, a nasal spray that patients can self-administer to manage paroxysmal supraventricular tachycardia (PSVT). This novel treatment option empowers patients with an on-demand solution to control their heart rhythms, significantly enhancing their quality of life.Turning to infectious diseases, Innoviva's Nuzolvence has been approved as a much-needed new treatment for gonorrhea, the first in over three decades following GSK's Blujepa. This marks an essential step forward in combating antibiotic-resistant sexually transmitted infections and highlights the urgency of developing new antimicrobial agents.However, not all ventures have met with success. Argenx recently halted studies of its drug Vyvgart in thyroid eye disease after disappointing trial results. This decision underscores the inherent challenges and risks involved in drug development, particularly when tackling complex autoimmune conditions.Sanofi has faced its own hurdles with Tolebrutinib after experiencing both FDA delays and trial misses in non-relapsing secondary progressive multiple sclerosis. These setbacks emphasize the intricacies of bringing innovative therapies to market and the critical importance of robust clinical trial design and regulatory strategy.Strategic collaborations are also playing a pivotal role in the industry. Adaptive Biotechnologies has partnered with Pfizer to leverage its T-cell receptor discovery technology. Meanwhile, Dren Bio is expanding its collaboration with Sanofi to develop next-generation B-cell depleting therapies for autoimmune diseases. These alliances reflect an increasing trend towards collaborative innovation to harness cutting-edge technologies.Another strategic move comes from Sobi, which has acquired Arthrosi Therapeutics for $950 million to bolster its portfolio with phase 3 gout treatments. This acquisition bypasses traditional IPO routes and showcases evolving deal-making strategies within biopharma.In another exciting development, Kyverna Therapeutics is on the verge of securing the first-in-class CAR-T therapy approval for autoimmune diseases following promising trial results with its CD19 agent. This could herald a new era in autoimmune disease management through cellular therapies.In regulatory news beyond pharmaceuticals, former President Donald Trump signed an executive order establishing a unified federal framework for artificial intelligence (AI). This aims to streamline AI regulation across states and could accelerate AI integration into various sectors, including healthcare.These developments collectively represent pivotal moments in the pharmaceutical and Support the show

Featuring perspectives from Dr Gottfried E Konecny, moderated by Dr Stephen "Fred" Divers, including the following topics:  Updates in Ovarian Cancer (OC) 2025 — Dr Konecny (0:00) Case: A woman in her mid 50s with ovarian cancer and a PALB2 germline mutation — Dr Mulherin (17:15) Case: A woman in her early 60s with Stage IVB fallopian tube carcinoma and a BRCA2 germline mutation — Dr Yannucci (26:27) Case: A woman in her mid 60s with OC and a BRCA2 somatic mutation who develops cytopenias on maintenance olaparib — Dr Lamar (35:47) Case: A woman in her early 70s with HER2 IHC 2+, ER-expressing, FOLR1-positive OC — Dr Warsch (42:54) CE information and select publications

I'm so excited to share today's Ask The Egg Whisperer. This week, I answered your thoughtful questions about fertility challenges, treatment options, and the science behind conditions like endometriosis. We talked about whether endometriosis can be passed from mother to daughter, how lifestyle changes and supplements may affect egg quality, and what options are available if you've had an abnormal HSG or blocked fallopian tube. My goal is always to give you clear, compassionate answers while helping you feel more empowered on your fertility journey. In addition, I dove into questions around protocols for Omnitrope and low-stimulation cycles, the potential role of supplements like CoQ10 and inositol, and whether HGH is safe for patients with certain genetic risks. I also shared my perspective on fertility at age 42, including what steps you can take to make the most of your options. These conversations remind me why I love connecting with you all: your questions not only help guide our discussions but also show how much strength, resilience, and curiosity you bring to this process. Here are a few of the questions I answered:

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

This week we are talking about Pancreatic cancer.  This is a type of cancer that begins as a growth of cells in the pancreas. The pancreas lies behind the lower part of the stomach. It makes enzymes that help digest food and hormones that help manage blood sugar. The most common type of pancreatic cancer is pancreatic ductal adenocarcinoma. This type begins in the cells that line the ducts that carry digestive enzymes out of the pancreas. Pancreatic cancer rarely is found at its early stages when the chance of curing it is greatest. This is because it often doesn't cause symptoms until after it has spread to other organs. Your health care team considers the extent of your pancreatic cancer when creating your treatment plan. Treatment options may include surgery, chemotherapy, radiation therapy or a mix of these. Pancreatic cancer often doesn't cause symptoms until the disease is advanced. When they happen, signs and symptoms of pancreatic cancer may include: Belly pain that spreads to the sides or back. Loss of appetite. Weight loss. Yellowing of the skin and the whites of the eyes, called jaundice. Light-colored or floating stools. Dark-colored urine. Itching. New diagnosis of diabetes or diabetes that's getting harder to control. Pain and swelling in an arm or leg, which might be caused by a blood clot. Tiredness or weakness. It's not clear what causes pancreatic cancer. Doctors have found some factors that might raise the risk of this type of cancer. These include smoking and having a family history of pancreatic cancer. Understanding the pancreas The pancreas is about 6 inches (15 centimeters) long and looks something like a pear lying on its side. It releases hormones, including insulin. These hormones help the body process the sugar in the foods you eat. The pancreas also makes digestive juices to help the body digest food and take in nutrients. How pancreatic cancer forms Pancreatic cancer happens when cells in the pancreas develop changes in their DNA. A cell's DNA holds the instructions that tell a cell what to do. In healthy cells, the instructions tell the cells to grow and multiply at a set rate. The cells die at a set time. In cancer cells, the changes give different instructions. The changes tell the cancer cells to make many more cells quickly. Cancer cells can keep living when healthy cells would die. This causes there to be too many cells. The cancer cells might form a mass called a tumor. The tumor can grow to invade and destroy healthy body tissue. In time, cancer cells can break away and spread to other parts of the body. Most pancreatic cancer begins in the cells that line the ducts of the pancreas. This type of cancer is called pancreatic ductal adenocarcinoma or pancreatic exocrine cancer. Less often, cancer can form in the hormone-producing cells or the neuroendocrine cells of the pancreas. These types of cancer are called pancreatic neuroendocrine tumors or pancreatic endocrine cancer. Risk factors Factors that might raise the risk of pancreatic cancer include: Smoking. Type 2 diabetes. Chronic inflammation of the pancreas, called pancreatitis. Family history of DNA changes that can increase cancer risk. These include changes in the BRCA2 gene, Lynch syndrome and familial atypical multiple mole melanoma (FAMMM) syndrome. Family history of pancreatic cancer. Obesity. Older age. Most people with pancreatic cancer are over 65. Drinking a lot of alcohol. As pancreatic cancer progresses, it can cause complications such as: Weight loss. People with pancreatic cancer might lose weight as the cancer uses more of the body's energy. Nausea and vomiting caused by cancer treatments or a cancer pressing on the stomach might make it hard to eat. Sometimes the body has trouble getting nutrients from food because the pancreas isn't making enough digestive juices. Jaundice. Pancreatic cancer that blocks the liver's bile duct can cause jaundice. Signs include yellowing of the skin and the whites of the eyes. Jaundice can cause dark-colored urine and pale-colored stools. Jaundice often occurs without belly pain. If the bile duct is blocked, a plastic or metal tube called a stent can be put inside it. The stent helps hold the bile duct open. This is done using a procedure called endoscopic retrograde cholangiopancreatography, also called ERCP. During ERCP, a health care professional puts a long tube with a tiny camera, called an endoscope, down the throat. The tube goes through the stomach and into the upper part of the small intestine. The health professional puts a dye into the pancreatic ducts and bile ducts through a small tube that fits through the endoscope. The dye helps the ducts show up on imaging tests. The health professional uses those images to place a stent at the right spot in the duct to help hold it open. Pain. A growing tumor may press on nerves in your abdomen, causing pain that can become severe. Pain medications can help you feel more comfortable. Treatments, such as radiation and chemotherapy, might help slow tumor growth and provide some pain relief. When medicines aren't helping, a health care professional might suggest a celiac plexus block. This procedure uses a needle to put alcohol into the nerves that control pain in the belly. The alcohol stops the nerves from sending pain signals to the brain. Bowel blockage. Pancreatic cancer can grow into or press on the first part of the small intestine, called the duodenum. This can block the flow of digested food from the stomach into the intestines. A health care professional might suggest putting a tube called a stent in the small intestine to hold it open. Sometimes, it might help to have surgery to place a feeding tube. Or surgery can attach the stomach to a lower part of the intestines where the cancer isn't causing a blockage. Prevention Screening for people with a high risk of pancreatic cancer Screening uses tests to look for signs of pancreatic cancer in people who don't have symptoms. It might be an option if you have a very high risk of pancreatic cancer. Your risk might be high if you have a strong family history of pancreatic cancer or if you have an inherited DNA change that increases the risk of cancer. Pancreatic cancer screening might involve imaging tests, such as MRI and ultrasound. These tests are generally repeated every year. The goal of screening is to find pancreatic cancer when it's small and most likely to be cured. Research is ongoing, so it's not yet clear whether screening can lower the risk of dying of pancreatic cancer. There are risks to screening. This includes the chance of finding something that requires surgery but later turns out to not be cancer. Talk about the benefits and risks of pancreatic cancer screening with your health care team. Together you can decide whether screening is right for you. Genetic testing for cancer risk If you have a family history of pancreatic cancer, discuss it with a health care professional. The health professional can review your family history and help you understand whether genetic testing might be right for you. Genetic testing can find DNA changes that run in families and increase the risk of cancer. If you're interested in genetic testing, you might be referred to a genetic counselor or other health care professional trained in genetics. Ways to lower risk You might reduce your risk of pancreatic cancer if you: Stop smoking. If you smoke, talk to a member of your health care team about ways to help you stop. These might include support groups, medicines and nicotine replacement therapy. Maintain a healthy weight. If you are at a healthy weight, work to maintain it. If you need to lose weight, aim for a slow, steady weight loss of 1 to 2 pounds (0.5 to 1 kilogram) a week. To help you lose weight, exercise most days of the week. Slowly increase the amount of exercise you get. Choose a diet rich in vegetables, fruit and whole grains with smaller portions.  (CREDITS: MAYO CLINIC)

In this powerful season finale, Ivory reflects on a transformative year—motherhood through kinship adoption, buying her first home, navigating love, and preparing for preventive surgeries after testing BRCA2+. Joined by spiritual healer and author Lorna J. Hines, she explores faith, ancestry, and healing beyond appearance. This conversation offers gentle truth: you can struggle and still be sacred. You can ache and still be anointed. And you, too, deserve good things.

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

What if the small choices you make at home could drastically change your family's health and help the planet - all at the same time? In this educationally rich episode, I sit down with Anna Robertson, co-founder of The Cool Down, to talk about how moms and families can make sustainability simple, practical and guilt-free.After stepping into motherhood, being evacuated from wildfires and discovering she carried the BRCA2 gene, Anna turned her personal wake-up call into a mission to help families live cleaner, healthier and more eco-conscious lives without all the overwhelm.In today's discussion - we unpack:

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.  

Featuring case presentations and related discussion from Dr Sara A Hurvitz and Dr Sara M Tolaney, including the following topics: Case: A woman in her mid 50s with localized HR-negative, HER2-positive breast cancer — Dr Tolaney (0:00) Case: A woman in her mid 40s with localized HR-positive breast cancer with a germline BRCA2 mutation — Dr Tolaney (7:08) Case: A woman in her early 30s with HR-negative, HER2-positive metastatic breast cancer with one isolated liver metastasis — Dr Tolaney (11:30) Case: A woman in her early 50s with metastatic triple-negative breast cancer — Dr Tolaney (17:52) Case: A woman in her early 30s with localized HR-positive, HER2-negative breast cancer — Dr Hurvitz (31:49) Case: A woman in her early 60s with HR-positive, HER2-negative metastatic breast cancer with concurrent PIK3CA and ESR1 mutations — Dr Hurvitz (40:39) Case: A woman in her early 40s with recurrent HR-positive advanced breast cancer with a PIK3CA mutation — Dr Hurvitz (51:28) Case: A woman in her early 50s with HR-positive, HER2-negative breast cancer eligible for the SERENA-6 switching strategy — Angela DeMichele, MD, MSCE (58:41) CME information and select publications

Les auditeurs de la Libre antenne de Roland Perez de ce jeudi 2 octobre 2025 :    CAROLINE : 22H47/23H25 Porteuse du gène BRCA2, à 26 ans Caroline a choisi de se faire enlever les seins pour éviter un cancer. https://geneticancer.org/   MICKAEL : 23H30/23H59 Les trois filles de Mickaël ont été placées sur la base de fausses déclarations de la belle mère.   NICOLAS : 00H11/00H26   FRANCOISE : 00H28/01H00 À74 ans, Françoise vient d'apprendre qu'elle a un cancer du sein. Hébergé par Audiomeans. Visitez audiomeans.fr/politique-de-confidentialite pour plus d'informations.

Auditrice : - Porteuse du gène BRCA2, à 26 ans, Caroline a choisi de se faire enlever les seins pour éviter un cancer. https://geneticancer.org/ Hébergé par Audiomeans. Visitez audiomeans.fr/politique-de-confidentialite pour plus d'informations.

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 happens when a music executive's precision meets a life-changing diagnosis? In this candid episode of All Talk Oncology, Kenny Perkins sits down with Mathew Knowles—music executive, author of The DNA of Achievers, and male breast cancer survivor. A tiny sign on a white T-shirt (nipple discharge) led Mathew to insist on a mammogram, a Stage 1A diagnosis, surgery, and the discovery of a BRCA2 variant. Drawing on his 20-year background in medical imaging, he breaks down early detection, building a winning care team, and why he now lives by quarterly labs, therapy, movement, and joy. From COVID-era anxiety to laughter-filled nights with his wife, Mathew shares the mindset shifts and habits that helped him rebuild a life he loves—one mindful walk and measured plate at a time. Key Topics Discussed Men get breast cancer: the overlooked red flags (nipple discharge) and why Mathew demanded a mammogram BRCA2 explained: risk implications for men (melanoma, pancreatic, prostate, male breast cancer) and for women (breast, gynecologic) Diagnosed at Stage 1A: survival odds, surgery, and five years on Tamoxifen From isolation to a care team: oncologist, therapist, spiritual support—and why isolation increases risk COVID anxiety & mental health: therapy to confront fear of dying and regain balance Diet, weight loss (~40 lbs), and daily 2-mile brisk walks—“cancer loves obesity” Portion control and practical nutrition: measuring plates, lighter foods, consistent habits Quarterly labs for peace of mind (not just annual checkups); self-advocacy with your clinicians “Look out the window”: stillness, nature, laughter, and marriage strengthened through survivorship Family history & genetics: why genetic testing + knowing your lineage should start early Men's health advocacy: PSA tests, breaking cultural conditioning, and getting over outdated fears   Immortalize your voice by being an ALL TALK ONCOLOGY GUEST! Just fill-out this FORM.   SOCIAL MEDIA LINKS: All Talk Oncology: Instagram & Facebook JOIN OUR FREE COMMUNITY: Facebook Community WEBSITE: https://www.alltalkoncology.com

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.

JCO PO author Dr. Alison M. Schram at Memorial Sloan Kettering Cancer Center shares insights into her JCO PO article, “Retrospective Analysis of BRCA-Altered Uterine Sarcoma Treated With Poly(ADP-ribose) Polymerase Inhibitors.” Host Dr. Rafeh Naqash and Dr. Schram discuss relevant genomic and clinical features of patients with BRCA-altered uterine sarcoma and the efficacy of PARPis in this population. 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, we are excited to be joined by Dr. Alison Schram, Associate Attending Physician and Section Head of Oral Therapeutics with Early Drug Development and Gynecologic Medical Oncology Services at the Memorial Sloan Kettering Cancer Center, and the senior author of the JCO Precision Oncology article titled, "Retrospective Analysis of BRCA-Altered Uterine Sarcoma Treated With Poly(ADP-ribose) Polymerase Inhibitors." At the time of this recording, our guest's disclosures will be linked in the transcript. Dr. Schram, thank you for joining us today. I am excited to be discussing this very interesting, unique topic based on what you published in JCO PO. Dr. Alison Schram: Thank you for having me. Dr. Rafeh Naqash: What we like to do for these podcasts is try to make them scientifically interesting but at the same time, keep them at a level where our trainees and other community oncology professionals understand the implications of what you've published. So I'd like to start by asking you, what is leiomyosarcoma for those of us who don't necessarily know a lot about leiomyosarcoma, and what are some of the treatment options for these uterine sarcomas? Dr. Alison Schram: Uterine leiomyosarcoma is a rare subtype of uterine cancer, and it represents about 1% of all female cancers in the reproductive tract. This is a rare malignancy that arises from the myometrial lining of the uterus, and it is generally pretty aggressive. In terms of the standard therapy, the standard therapy for uterine leiomyosarcoma includes chemotherapy, generally combination chemotherapy, but despite a few regimens that tend to be effective, the duration of effectiveness is relatively short-lived, and patients with advanced uterine leiomyosarcoma eventually progress and require additional therapy. I will say that localized uterine leiomyosarcoma can be treated with surgery as well. Dr. Rafeh Naqash: Thank you for that description. Now, there are two aspects to what you published. One is the sarcoma aspect, the leiomyosarcoma, and the second is the BRCA mutation. Since we are a precision medicine journal, although we've discussed BRCA a couple of times before, but again, for the sake of our listeners, could you highlight some of the aspects of BRCA and PARP sensitivity for us? Dr. Alison Schram: Yes. So BRCA is a gene that's important for DNA repair, and BRCA mutations can be either inherited as a germline mutation, so one of your parents likely had a BRCA mutation and you inherited one copy. In patients who have an inherited BRCA mutation, the normal cells tend to have one abnormal copy of BRCA, but if a second copy in the cell becomes altered, then that develops into cancer. And so these patients are at increased risk of developing cancers. Specifically, they are at an increased risk of developing ovarian cancer, breast cancer, prostate cancer, pancreatic cancer, and a few others. These cancers are considered BRCA-associated tumors. Alternatively, some patients, more rarely, can develop BRCA-altered cancers completely sporadically. So it's a mutation that happens in the tumor itself, and that can lead to impaired DNA repair and promote cancer progression. And those patients are not, they don't have any inherited risk, but just a random event caused a BRCA mutation in the tumor. The reason this is important is because, in addition to it being potentially important for family members, there are certain treatments that are more effective in BRCA-altered cancers. And the main example is PARP inhibitors, which are small molecule inhibitors that inhibit the PARP enzyme, and there is what we call synthetic lethality. So PARP is important for DNA repair, for single-stranded DNA repair, BRCA is important for double-stranded DNA repair, and in a patient that has a cancer that has a BRCA mutation, that cancer becomes more reliant on single-stranded DNA repair. And if you inhibit it with a PARP inhibitor, the cancer cells are unable to repair DNA, and the cells die. So we call that synthetic lethality. PARP inhibitors are FDA approved in several diseases, predominantly the BRCA-associated diseases I mentioned: breast cancer, ovarian cancer, pancreatic cancer, and prostate cancer. Dr. Rafeh Naqash: That was very beautifully explained. Honestly, I've heard many people explain BRCA before, but you kind of put it in a very simple, easy to understand format. You mentioned this earlier describing germline or hereditary BRCA and somatic BRCA. And from what I gather, you had a predominant population of somatic BRCA, but a couple of germline BRCA as well in your patient population, which we'll go into details as we understand the study. You mentioned the second hit on the germline BRCA that is required for the other copy of the gene to be altered. In your clinical experience, have you seen outside of the study that you published, a difference in the sensitivity of PARP for germline BRCA versus a somatic BRCA that has loss of both alleles? Dr. Alison Schram: So we will get into what's unique about uterine sarcomas in just a minute. In uterine sarcomas, what we have found is that the BRCA mutations tend to be somatic and not germline, as you mentioned. That is in contrast to the other diseases we mentioned, where the vast majority of these tumors are in patients that have germline BRCA alterations. So one thing that's really unique about the uterine sarcoma population and our paper, I believe, is that it is demonstrating an indication for PARP inhibitors in a population that is not characterized by germline BRCA alterations, but truly these by somatic BRCA alterations. If you look at the diseases that PARP inhibitors are validated to be effective in, including the, you know, the ones I mentioned, the BRCA-associated tumors, there's some data in specific context that suggests that perhaps germline alterations are more sensitive to PARP inhibitors, but that's not universal, and it's really tricky to do because the genetic testing that we have doesn't always tell you if you have two hits or just one hit. So you need more complex genetic analysis to truly understand if there is what we call a biallelic loss. And sometimes it's not a second mutation in BRCA. Sometimes it's silencing of the gene by hypermethylation or epigenetics. Some of our clinical trials are now incorporating this data collection to really understand if biallelic loss that we can identify on more complex genetic testing predicts for better outcomes. And we think it's probably true that the patients that have biallelic loss, whether it be germline or somatic biallelic loss, are more likely to benefit from these treatments. That still needs to be tested in a larger cohort of patients prospectively. Dr. Rafeh Naqash: In your clinical experience, I know you predominantly use MSK-IMPACT, but maybe you've perhaps used some other NGS platforms, next-generation sequencing platforms. Have you noticed that these reports for BRCA alterations the report mentioning biallelic loss in certain cases? I personally don't- I do lung cancer, I do early-phase lung cancer as well, but I personally don't actually remember if I've seen a report that actually says biallelic loss. So after this podcast, I'm going to check some of those NGS reports and make sure I look at it. But have you seen it, or what would be a learning point for the listeners there? Dr. Alison Schram: Exactly. And they usually do not. They usually do not explicitly say, “This looks like biallelic loss,” on the reports. The exception would be if there's a deep deletion, then that implies both copies of the gene have been deleted, and so then you can assume that it's a biallelic loss. But oftentimes, when you see a frameshift alteration or a mutation, you don't know whether or not it's a biallelic loss. And you may be able to get some clues based on the variant allele frequencies, but due to things like whole genome duplication or more complex tumor genomics, it's not clear from these reports, and you really do need a more in-depth bioinformatic analysis to understand whether these are biallelic or not. So that is why I suggest that this really needs to be done in the context of a clinical trial, but there is definitely a theoretical rationale for reporting and treating patients with biallelic losses perhaps more so than someone who has a variant of unknown significance that seems to be monoallelic. The other tricky part, as I mentioned, is the fact that there could be epigenetic changes that silence the second copy, so that wouldn't be necessarily evident on a DNA report, and you would need more complex molecular testing to understand that as well. Dr. Rafeh Naqash: Sure. Now, going to your study, could you tell us what prompted the study, what was the patient population that you collected, and how did you go about this research study design? Dr. Alison Schram: It's actually a great story. I was the principal investigator for a clinical trial enrolling patients regardless of their tumor type to a combination of a PARP inhibitor and immunotherapy. And this was a large clinical trial that was being done as a basket study, as I mentioned, for patients that have either germline or somatic alterations with advanced solid tumors that had progressed on standard therapy. And the hypothesis was that the combination of a PARP inhibitor and immunotherapy would be synergistic and that there would be increased efficacy compared to either agent alone and that patients who had BRCA alterations were a sensitive population to test because of their inherent sensitivity to PARP inhibitors and perhaps their increased neoantigen burden from having loss of DNA repair. So this large study, it's been published, really did show that there was efficacy across several tumor types, but it didn't seem to clearly demonstrate synergy between the immunotherapy and the PARP inhibitor as compared to what you might expect from a PARP inhibitor alone, and in addition to a couple of cases, perhaps attributable to the immunotherapy. So maybe additive rather than synergistic efficacy. However, what really struck me looking at the data was that there were three patients with uterine leiomyosarcoma with BRCA deletions who had the best responses of anyone on the study. So incredible, durable responses. One of my patients with a complete response that continues to not have any evidence of cancer eight years after the initiation of this regimen. And for those of us that treat uterine leiomyosarcoma, this is unheard of. These patients generally, as I mentioned, respond, if they do respond to chemotherapy, it's generally short-lived and the cancer progresses. And so a complete response nearly a decade later turns heads in this field. The other interesting thing was that these uterine leiomyosarcoma patients had somatic alterations rather than a germline alteration with a second hit, and the diseases that are best validated for being responsive to PARP inhibitors include the BRCA-associated diseases, the ones that you're at increased risk for if you have a germline BRCA mutation, including breast, pancreas, prostate, and ovarian. And so it was very interesting that this disease type that seemed to be uniquely sensitive to PARP inhibitors with immunotherapy was also different in that patients with uterine leiomyosarcoma don't tend to have a high frequency of BRCA alterations, and in patients that are born with a BRCA alteration, there doesn't seem to be a clearly increased risk of uterine sarcomas. So this population really jumped out as a uniquely sensitive population that differed from the prior indications for PARP inhibitors. Given this patient and these couple of patients that we observed on the combination, in addition to some other case reports and case series that had started to come out in small numbers, we wanted to look back at our large cohort of patients at Memorial Sloan Kettering to see if we could really get a better sense of the numbers. How many patients at Sloan Kettering with uterine sarcomas have BRCA alterations? Are they generally somatic or germline? Are there unique features about these patients in terms of their clinical characteristics? How many of them have received PARP inhibitors, and if so, is this just luck that these three patients did so well, or is this really a good treatment option for patients with BRCA-altered uterine sarcomas? And so we did this retrospective analysis identifying the patients at Sloan Kettering who met these criteria. So in total, we found 35 patients with uterine sarcomas harboring BRCA alterations, and the majority were leiomyosarcoma, about 86% of them had leiomyosarcoma, which is interesting because there are other uterine sarcomas, but it does seem like BRCA alterations tend to be more often in the leiomyosarcomas. And 13 of these patients with uterine leiomyosarcoma were treated with PARP inhibitors in the recurrent or metastatic setting with about half of those patients having an overall response, so that's a significant tumor shrinkage that sustained, and a clinical benefit rate of 62%. And if we look at the patients that had these BRCA2 deep deletions, which was the patient I had that had this amazing response, the overall response rate jumped to 60% and the clinical benefit rate to 80%. And we defined clinical benefit rate as having maintained on the PARP inhibitor without evidence of progression at six months. So this is really impressive for patients with a difficult to treat disease. And we couldn't do a randomized controlled trial comparing it to chemotherapy, but looking retrospectively at outcomes on chemotherapy studies, this was very favorable, particularly because many of these patients were heavily pretreated. So to get a sense of, you know, how this might compare to chemotherapy, we tried to use patients as their own internal controls, and we looked at how long patients were maintained on the PARP inhibitor as compared to how long they were on the treatment just prior. And we used a ratio of 1.3 to say if they were on the PARP inhibitor for 1.3 times what their previous treatment was or longer, that is pretty clearly better, more of a benefit from that regimen. And the majority of patients did meet that bar. So 58% had a PFS ratio greater than 1.3, and the average PFS ratio was 1.9, suggesting, you know, you would expect the the later lines of therapy to actually not work as well, but this suggests that it's actually working better than the immediately prior line of therapy, to me, suggesting that this is truly a good treatment option for these patients. Dr. Rafeh Naqash: Very interesting. And you mentioned that individuals with tumors having deep deletions were probably more responsive. How did you figure out that there was biallelic loss or deep deletions? Was that part of an extended analysis that was done subsequently? Dr. Alison Schram: So the deletions reported on our report, if it's a biallelic deletion, that is the one biallelic molecular alteration that would be reported. So those are, by definition, biallelic, and I think that that may be one of the reasons that's a good biomarker. But also, what's interesting is that if you have both copies deleted of BRCA, you can't develop reversion mutations. So one of the the known mechanisms of resistance to PARP inhibitors in patients who have BRCA alterations are something called a reversion mutation where, if you have a frameshift alteration, for example, in BRCA that makes BRCA protein nonfunctional, you can develop a second mutation that actually puts the DNA back in frame, and a functional protein is now made. And so a mechanism of resistance to PARP inhibitors is actually reverting BRCA to a wild-type protein, and then BRCA's synthetic lethality no longer makes sense and is no longer effective. But if you've deleted both copies of BRCA, you don't have the ability to restore the function, and you can't develop reversion mutations. And that's perhaps why, you know, my patient and others have had these prolonged responses to PARP inhibitors because you don't have the same ability to develop that mechanism of resistance. Dr. Rafeh Naqash: I remember thinking a year and a half back, I had an individual with prostate cancer and with BRCA2, and using liquid biopsy, I had a reversion mutation that we caught. In your practice, have you seen the utility of doing the serial liquid biopsies in these individuals to catch these reversion mutations? Dr. Alison Schram: Yes, absolutely. And in patients that have the ability to develop a reversion mutation, serial cell-free DNA can catch it, but the caveat is that it doesn't always. So if you see an acquired reversion mutation in cell-free DNA, that can be helpful, particularly if you're planning on putting the patient on another line of therapy that might require a dysfunctional BRCA. So if you're putting them on a clinical trial with a PARP combination and the rationale is that they're sensitive because they don't have a functional BRCA, you would want to know if they developed a reversion mutation, and serial cell-free DNA can definitely identify these reversion mutations. Some of the major clinical trials in ovarian cancer have done serial cell-free DNA and have demonstrated the utility of that approach. The caveat is that some of these reversion mutations are not readily caught on cell-free DNA because they're more complex reversion mutations, or they're not, the part of the gene that develops the reversion mutation is not tiled on the panel. And so it doesn't always catch the reversion mutations. Also, depends on the cell-free DNA shedding, depends on the tumor volume and other factors. And we published a related paper of a patient, it was a really interesting case of a patient with prostate cancer who was on a PARP inhibitor and developed what appeared to be a single reversion mutation on one sample, had negative cell-free DNA, single reversion mutation in a tissue biopsy, and then developed disease progression. And we did an autopsy, and the patient kindly consented to an autopsy, and at the time of autopsy, there were 10 unique reversion mutations identified across 11 metastases. So almost each metastasis had a unique reversion mutation, and only one of them had been seen premortem on a tissue biopsy and not on a cell-free DNA. But that autopsy really drove home to me how much we're missing by doing clinical testing in real time and we really don't know the entire genomic complexity of our patients by doing single samples. And theoretically, cell-free DNA can catch DNA from all the metastases, so you might think that that would be a solution, and it definitely can catch reversion mutations that are not seen in a single biopsy, but you really need to do it all. I mean, you need to do the tissue biopsy sampling, you need to do cell-free DNA, and probably one cell-free DNA test is not enough. Dr. Rafeh Naqash: Thank you, again, for that very nice explanation. Now, one quick provocative question. I remember when I was training, the lab that I used to work in, they used to do a lot of phosphorylation markers for DNA damage response, like phospho NBS, RAD51. Have you seen anything of that sort on these biallelic BRCA mutations where tumors are responding, but they also have a very high signature on the phosphorylation side, and it may or may not necessarily correspond to HRD signatures, but have you noticed or done any of that analysis? Dr. Alison Schram: I think that it would be great to do that analysis. And some of the work we're doing now is actually trying to dig a little bit deeper in our cohort of patients to understand are these HRD-positive tumors? Does HRD positivity correlate with response to BRCA alterations? In terms of the functional assays, I would love to be able to do a functional assay in these samples. One of the challenges is that this was a retrospective study and many of the patients were previously treated as standard of care or off-label with these agents, and so we didn't have prospective tissue collection, and so we're really limited by the tissue that was collected as part of standard of care and the consent forms that the patient signed that allow us to do genomic and molecular testing on their samples. So, I think that is hopefully future work that we will do and others will do. Dr. Rafeh Naqash: Sure. Shifting gears to your career trajectory, I'd like to spend a couple of minutes there before we end the podcast. So Dr. Schram, you've obviously been a trailblazer in this space of drug development, early-phase trials. Can you give us a brief synopsis of your journey and how you've successfully done what you're doing and what are some of the things that drive you? Dr. Alison Schram: Well, thank you for saying that. I don't know if that's true, but I'll take the bait. I've been interested in oncology since college and was always very interested in not only the science of oncology but of course, treating patients. And in medical school, I did basic science research in a laboratory and it was very inspiring and made me want to do research in oncology in addition to clinical care. When I became an oncology fellow, I was presented with a very difficult question, which is, “Do you want to be a lab PI and be in the lab, or do you want to do clinical care and clinical research?” And I couldn't choose. I found a mentor who thankfully really had this amazing vision of combining the two and doing very early drug development, taking the data that was being generated by labs and translating it into patients at the earliest stage. So, you know, phase one drug development in molecularly targeted therapies. And so I became very interested as a fellow in early drug development and this ability to translate brand new molecular insights into novel drugs. And I joined the- at Sloan Kettering, there was the Early Drug Development, it was actually a clinic, it was called something different, and it was very fortuitous. My last year of fellowship, the clinic became its own service with the ability to hire staff at Sloan Kettering, and I was the first ever hire to our Early Drug Development Service. And that really inspired me to try and bring these drugs to patients and to really translate the amazing molecular insights that my colleagues here at Sloan Kettering are discovering, and you know, of course, at other institutions and in pharma. And you know, there 's been an amazing revolution in in drug development over the last several years, and I feel very grateful that I've been here for it. You know, I've been able to take the brilliant insights from my colleagues and put these drugs in patients, and I have the amazing privilege of watching patients in many cases that benefit from these treatments. And so I do mostly phase one drug development and molecularly targeted therapies, and truthfully, I am just very fortunate to be around such brilliant people and to have both patients and labs trust me to be able to deliver these new drugs to patients and hopefully develop better drugs that move forward through FDA approval and reach patients across the country. Dr. Rafeh Naqash: Thank you so much. That was very nicely put. And hopefully our trainees and junior faculty find that useful based on their own career trajectories. Thank you, Dr. Schram, for joining us today. Hopefully, we'll see more of your subsequent work in JCO PO. Thank you for giving us all these insights today. Dr. Alison Schram: Thank you for having me. 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/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. Dr. Alison Schram Disclosures Consulting or Advisory Role Company: Mersana, Merus NV, Relay Therapeutics, Schrodinger, PMV Pharma ,Blueprint Medicines, Flagship Pioneering, Redona Therapeutics, Repare Therapeutics, Endeavor BioMedicines Research Funding Company: Recipient: Your Institution  Merus, Kura, Surface Oncology, AstraZeneca, Lilly, Pfizer , Black Diamond Therapeutics, BeiGene, Relay Therapeutics, Revolution Medicines,  Repare Therapeutics, PMV Pharma, Elevation Oncology, Boehringer Ingelheim Travel, Accommodations, Expenses Company: PMV Pharma 

PJ explores the transformative power of cancer research with Orla Dolan, CEO of Breakthrough Cancer Research, and Fiona Ryan, a BRCA2 gene carrier. From the new Cancer Revolution exhibition in Dublin to cutting-edge treatments like immunotherapy and preventative surgery, this episode highlights the progress made in cancer care, the human stories behind the science, and the hope that ongoing research brings. Hosted on Acast. See acast.com/privacy for more information.

“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.

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

UCSF oncologist Dr. Jonathan Chou discusses how genetics and genomics are transforming the diagnosis and treatment of prostate cancer. He explains how inherited and acquired mutations—especially in DNA repair genes like BRCA2—can impact both cancer risk and treatment decisions. Dr. Chou outlines how UCSF researchers use tumor and blood-based biopsies to identify key mutations and genomic features that help tailor care for each patient. Examples include how genomic scores can predict response to radiation and how targeted therapies like PARP inhibitors benefit patients with specific mutations. The talk highlights the growing role of precision medicine in guiding individualized treatment plans based on the unique genetic profile of each patient's cancer. Series: "Prostate Cancer Patient Conference" [Health and Medicine] [Show ID: 40798]

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss important advances in the treatment of prostate, bladder, and kidney cancers that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute and editor-in-chief of the ASCO Daily News.  I am delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of the GU Center at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that were presented at the 2025 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode.  Jeanny, it is great to have you on the podcast. Dr. Jeanny Aragon-Ching: Oh, thank you so much, Neeraj. Dr. Neeraj Agarwal: Jeanny, let's begin with some prostate cancer abstracts. Let's begin with Abstract 5017 titled, “Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer.” Can you walk us through the design and the key findings of this first-in-human trial? Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So this study, presented by Dr. Capucine Baldini, introduces pasritamig, a first-in-class T-cell redirecting bispecific antibody that simultaneously binds KLK2 on prostate cancer cells and CD3 receptor complexes on T cells. KLK2 is also known as human kallikrein 2, which is selectively expressed in prostate tissue. And for reference, KLK3 is what we now know as the PSA, prostate-specific antigen, therefore making it an attractive and specific target for therapeutic engagement. Now, while this was an early, first-in-human, phase 1 study, it enrolled 174 heavily pretreated metastatic CRPC patients. So many were previously treated with ARPIs, taxanes, and radioligand therapy. So given the phase 1 nature of this study, the primary objective was to determine the safety and the RP2D, which is the recommended phase 2 dose. Secondary objectives included preliminary assessment of antitumor activity. So, pasritamig was generally well tolerated. There were no treatment-related deaths. Serious adverse events were rare. And in the RP2D safety cohort, where patients received the step-up dosing up to 300 mg of IV every 6 weeks, the most common treatment-related adverse events were low-grade infusion reactions. There was fatigue and grade 1 cytokine release syndrome, what we call CRS. And no cases of neurotoxicity, or what we call ICANS, the immune effector cell-associated neurotoxicity syndrome, reported. Importantly, the CRS occurred in just about 8.9% of patients. All were grade 1. No patients required tocilizumab or discontinued treatment due to adverse events. So, this suggests a favorable safety profile, allowing hopefully for outpatient administration without hospitalization, which will be very important when we're thinking about bispecifics moving forward. In terms of efficacy, pasritamig showed promising activity. About 42.4% of evaluable patients achieved a PSA50 response. Radiographic PFS was about 6.8 months. And among patients with measurable disease, the objective response rate was about 16.1% in those with lymph node or bone metastases, and about 3.7% in those with visceral disease, with a median duration of response of about 11.3 months. So, altogether, this data suggests that pasritamig may offer a well-tolerated and active new potential option for patients with metastatic CRPC.   Again, as a reminder, with the caveat that this is still an early phase 1 study. Dr. Neeraj Agarwal: Thank you, Jeanny. These are promising results for a bispecific T-cell engager, pasritamig, in prostate cancer. I agree, the safety and durability observed here stand out, and this opens the door for further development, possibly even in earlier disease settings.  So, shifting now from immunotherapy to the evolving role of genomics in prostate cancer. So let's discuss Abstract 5094, a real-world, retrospective analysis exploring the prognostic impact of homologous recombination repair gene mutations, especially BRCA1 and BRCA2 mutations, in metastatic hormone-sensitive prostate cancer. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So this study was presented by Dr. David Olmos, represents one of the largest real-world analyses we have evaluating the impact of homologous recombination repair, or what we would call HRR, alterations in metastatic hormone-sensitive prostate cancer. So, this cohort included 556 men who underwent paired germline and somatic testing. Now, about 30% of patients had HRR alterations, with about 12% harboring BRCA1 or BRCA2 mutations and 16% having alterations in other HRR genes. Importantly, patients were stratified via CHAARTED disease volume, and outcomes were examined across treatment approaches, including ADT alone, doublet therapy, and triplet therapy. The prevalence of BRCA and HRR alterations were about similar between the metastatic hormone-sensitive prostate cancer and the metastatic castrate-resistant prostate cancer, with no differences observed, actually, between the patients with high volume versus low volume disease.  So, the key finding was that BRCA and HRR alterations were associated with poor clinical outcomes in metastatic hormone-sensitive prostate cancer. And notably, the impact of these alterations may actually be even greater in metastatic hormone-sensitive prostate cancer than previously reported in metastatic CRPC. So, the data showed that when BRCA mutations are present, the impact of the volume of disease is actually limited. So, poor outcomes were observed across the board for both high-volume and low-volume groups. So, the analysis showed that patients with HRR alterations had significantly worse outcomes compared to patients without HRR alterations. Median radiographic progression-free survival was about 20.5 months for the HRR-altered patients versus 30.6 months for the non-HRR patients, with a hazard ratio of 1.6. Median overall survival was 39 months for HRR-altered patients compared to 55.7 months for the non-HRR patients, with a hazard ratio of 1.5. Similar significant differences were observed when BRCA-mutant patients were compared with patients harboring non-BRCA HRR mutations. Overall, poor outcomes were independent of treatment of ARPI or taxanes. Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data reinforce homologous recombination repair mutations as both a predictive and prognostic biomarker, not only in the mCRPC, but also in the metastatic hormone-sensitive setting as well. It also makes a strong case for incorporating genomic testing early in the disease course and not waiting until our patients have castration-resistant disease. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. And I think this really brings home the point and the lead up to the AMPLITUDE trial, which is LBA5006, a phase 3 trial that builds on this very concept of testing with a PARP inhibitor, niraparib, in the hormone-sensitive space. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the AMPLITUDE trial, a phase 3 trial presented by Dr. Gerhardt Attard, enrolled 696 patients with metastatic hormone-sensitive prostate cancer and HRR gene alterations. 56% of these patients had BRCA1 and BRCA2 mutations. Patients were randomized to receive abiraterone with or without niraparib, a PARP inhibitor. The majority of patients, 78% of these patients, had high-volume metastatic hormone-sensitive prostate cancer, and 87% of these patients had de novo metastatic HSPC. And 16% of these patients received prior docetaxel, which was allowed in the clinical trial. So, with a median follow-up of nearly 31 months, radiographic progression-free survival was significantly prolonged with the niraparib plus abiraterone combination, and median was not reached in this arm, compared to abiraterone alone, which was 29.5 months, with a hazard ratio of 0.63, translating to a 37% reduction in risk of progression or death. This benefit was even more pronounced in the BRCA1 and BRCA2 subgroup, with a 48% reduction in risk of progression, with a hazard ratio of 0.52. Time to symptomatic progression also improved significantly across all patients, including patients with BRCA1, BRCA2, and HRR mutations. Although overall survival data remain immature, early trends favored the niraparib plus abiraterone combination. The safety profile was consistent with prior PARP inhibitor studies, with grade 3 or higher anemia and hypertension were more common but manageable. Treatment discontinuation due to adverse events remained low at 11%, suggesting that timely dose modifications when our patients experience grade 3 side effects may allow our patients to continue treatment without discontinuation. These findings support niraparib plus abiraterone as a potential new standard of care in our patients with metastatic hormone-sensitive prostate cancer with HRR alterations, and especially in those who had BRCA1 and BRCA2 mutations. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. This trial is especially exciting because it brings PARP inhibitors earlier into the treatment paradigm. Dr. Neeraj Agarwal: Exactly. And it is exciting to see the effect of PARP inhibitors in the earlier setting.  So Jeanny, now let's switch gears a bit to bladder cancer, which also saw several impactful studies. Could you tell us about Abstract 4502, an exploratory analysis from the EV-302 trial, which led to approval of enfortumab vedotin plus pembrolizumab for our patients with newly diagnosed metastatic bladder cancer? So here, the authors looked at the outcomes in patients who achieved a confirmed complete response with EV plus pembrolizumab. Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, EV-302 demonstrated significant improvements in progression-free and overall survival for patients previously treated locally advanced or metastatic urothelial cancer, I'll just call it metastatic UC, as a frontline strategy, establishing EV, which is enfortumab vedotin, plus pembro, with pembrolizumab as standard of care in this setting.  So, this year at ASCO, Dr Shilpa Gupta presented this exploratory responder analysis from the phase 3 EV-302 trial. Among 886 randomized patients, about 30.4% of patients, this is about 133, in the EV+P arm, and 14.5% of the patients in the chemotherapy arm, achieved a confirmed complete response. They call it the CCR rates. So for patients who achieved this, median PFS was not reached with EV+P compared to 26.9 months with chemotherapy, with a hazard ratio of 0.36, translating to a 64% reduction in the risk of progression. Overall survival was also improved. So the median OS was not reached in either arm, but the hazard ratio favored the EV+P at 0.37, translating to a 63% reduction in the risk of death. The median duration of complete response was not reached with EV+P compared to 15.2 months with chemotherapy. And among those patients who had confirmed CRs at 24 months, 78% of patients with the EV+P arm remained progression-free, and around 95% of the patients were alive, compared to 54% of patients who were progression-free and 86% alive of the patients in the chemotherapy arm. Safety among responders were also consistent with prior reports. Grade 3 or higher treatment-related adverse events occurred in 62% of EV+P responders and 72% of chemotherapy responders. Most adverse events were managed with dose modifications, and importantly, no treatment-related deaths were reported among those who were able to achieve complete response.  So these findings further reinforce EV and pembro as the preferred first-line therapy for metastatic urothelial carcinoma, offering a higher likelihood of deep, durable responses with a fairly manageable safety profile. Dr. Neeraj Agarwal: Thank you for the great summary, Jeanny. These findings underscore the depth and durability of responses achievable with this combination and also suggest that achieving a response may be a surrogate for long-term benefit in patients with metastatic urothelial carcinoma.  So now, let's move to Abstract 4503, an exploratory ctDNA analysis from the NIAGARA trial, which evaluated perioperative durvalumab, an immune checkpoint inhibitor, in muscle-invasive bladder cancer. So what can you tell us about this abstract? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, in NIAGARA, presented by Dr. Tom Powles, the addition of perioperative durvalumab to neoadjuvant chemotherapy, gem/cis, significantly improved event-free survival, overall survival, and pathologic complete response in patients with cisplatin-eligible muscle-invasive bladder cancer. Recall that this led to the U.S. FDA approval of this treatment regimen on March 28, 2025.  So, a planned exploratory analysis evaluated the ctDNA dynamics and their association with clinical outcomes, which was the one presented recently at ASCO. So, the study found that the incidence of finding ctDNA positivity in these patients was about 57%. Following neoadjuvant treatment, this dropped to about 22%, with ctDNA clearance being more common in the durvalumab arm, about 41%, compared to the chemotherapy control arm of 31%. Notably, 97% of patients who remained ctDNA positive prior to surgery failed to achieve a pathologic CR. So, this indicates a strong association between ctDNA persistence and lack of tumor eradication. So, postoperatively, only about 9% of patients were ctDNA positive. So, importantly, durvalumab conferred an event-free survival benefit regardless of ctDNA status at both baseline and post-surgery. Among patients who were ctDNA positive at baseline, durvalumab led to a hazard ratio of 0.73 for EFS. So, this translates to a 27% reduction in the risk of disease recurrence, progression, or death compared to the control arm. In the post-surgical ctDNA-positive group, the disease-free survival was also improved with a hazard ratio of 0.49, translating to a 51% reduction in the risk of recurrence.  So, these findings underscore the prognostic value of ctDNA and suggest that durvalumab provides clinical benefit irrespective of molecular residual disease status. So, the data also supports that ctDNA is a promising biomarker for future personalized strategies in the perioperative treatment of muscle-invasive bladder cancer. Dr. Neeraj Agarwal: Thank you, Jeanny. It is great to see that durvalumab is improving outcomes in these patients regardless of ctDNA status. However, based on these data, presence of ctDNA in our patients warrants a closer follow-up with imaging studies, because these patients with positive ctDNA seem to have a higher risk of recurrence. Dr. Jeanny Aragon-Ching: I agree, Neeraj.  Let's round out the bladder cancer discussion with Abstract 4518, which reported the interim results of SURE-02, which is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab in cisplatin-ineligible muscle-invasive bladder cancer. Can you tell us more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure, Jeanny. So, Dr Andrea Necchi presented interim results from the SURE-02 trial. This is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by a response-adapted bladder-sparing treatment and adjuvant pembrolizumab in patients with muscle-invasive bladder cancer.  So, in this interim analysis, 40 patients were treated and 31 patients were evaluable for efficacy. So, the clinical complete response rate was 38.7%. All patients achieving clinical complete response underwent bladder-sparing approach with a repeat TURBT instead of radical cystectomy. Additionally, 51.6% of patients achieved excellent pathologic response with a T stage of 1 or less after neoadjuvant therapy. The treatment was well tolerated, with only 12.9% of patients experiencing grade 3 or higher adverse events without needing dose reduction of sacituzumab. Molecular profiling, interestingly, showed that clinical complete response correlated with luminal and genomically unstable subtypes, while high stromal gene expression was associated with lack of response.  These results suggest that sacituzumab plus pembrolizumab combination has promising activity in this setting, and tolerability, and along with other factors may potentially allow a bladder preservation approach in a substantial number of patients down the line. Dr. Jeanny Aragon-Ching: Yeah, agree with you, Neeraj. And the findings are very provocative and support completing the full trial enrollment and further exploration of this strategy in muscle-invasive bladder cancer in order to improve and provide further bladder-sparing strategies. Dr. Neeraj Agarwal: Agree. So, let's now turn to the kidney cancer, starting with Abstract 4505, the final overall analysis from CheckMate-214 trial, which evaluated nivolumab plus ipilimumab, so dual checkpoint inhibition strategy, versus sunitinib in our patients with metastatic clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So, the final 9-year analysis of the phase 3 CheckMate-214 trial confirms the long-term superiority of nivolumab and ipilimumab over sunitinib for first-line treatment of advanced metastatic renal cell carcinoma. So, this has a median follow-up of 9 years. Overall survival remains significantly improved with the combination. So, in the ITT patient population, the intention-to-treat, the hazard ratio for overall survival was 0.71. So, this translates to a 29% reduction in the risk of death. 31% of patients were alive at this 108-month follow-up compared to 20% only in those who got sunitinib. So, similar benefits were observed in the intermediate- and poor-risk groups with a hazard ratio of 0.69, and 30% versus 19% survival at 108 months.  Importantly, a delayed benefit was also seen in those favorable-risk patients. So, the hazard ratio for overall survival improved from 1.45 in the initial report and now at 0.8 at 9 years follow-up, with 35% of patients alive at 108 months compared to 22% in those who got sunitinib. Progression-free survival also favored the nivo-ipi arm across all risk groups. At 96 months, the probability of remaining progression-free was about 23% compared to 9% in the sunitinib arm in the ITT patient population, 25% versus 9% in the intermediate- and poor-risk patients, and 13% compared to 11% in the favorable-risk patients. Importantly, at 96 months, 48% of patients in the nivo-ipi responders remained in response compared to just 19% in those who got sunitinib. And in the favorable-risk group, 36% of patients who responded remained in response, although data were not available for sunitinib in this subgroup.  So, this data reinforces the use of nivolumab and ipilimumab as a durable and effective first-line effective strategy for standard of care across all risk groups for advanced renal cell carcinoma. Dr. Neeraj Agarwal: Thank you, Jeanny. And of course, since ipi-nivo data were presented, several other novel ICI-TKI combinations have emerged. And I'm really hoping to see very similar data with TKI-ICI combinations down the line. It is really important to note that we are not seeing any new safety signals with the ICI combinations or ICI-based therapies, which is very reassuring given the extended exposure. Dr. Jeanny Aragon-Ching: Absolutely agree with you there, Neeraj.  Now, going on and moving on to Abstract 4514, which is the KEYNOTE-564 trial, and they reported on the 5-year outcomes of adjuvant pembrolizumab in clear cell RCC in patients who are at high risk for recurrence. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the KEYNOTE-564 trial established pembrolizumab monotherapy as the first adjuvant regimen to significantly improve both disease-free survival and overall survival compared to placebo after surgery for patients with clear cell renal cell carcinoma. So, Dr Naomi Haas presented the 5-year update from this landmark trial.  A total of 994 patients were randomized to receive either pembrolizumab or placebo. The median follow-up at the time of this analysis was approximately 70 months. Disease-free survival remained significantly improved with pembrolizumab. The median DFS was not reached with pembrolizumab compared to 68.3 months with placebo, with a hazard ratio of 0.71, translating to a 29% reduction in risk of recurrence. At 5 years, 60.9% of patients receiving pembrolizumab remained disease-free compared to 52.2% with placebo. Overall survival also favored pembrolizumab. The hazard ratio for OS was 0.66, translating to a 34% reduction in risk of death, with an estimated 5-year overall survival rate of 87.7% with pembrolizumab compared to 82.3% for placebo. Importantly, these benefits were consistent across all key subgroups, including patients with sarcomatoid features. In addition, no new serious treatment-related adverse events have been reported in the 3 years since treatment completion.  So, these long-term data confirm pembrolizumab as a durable and effective standard adjuvant therapy for patients with resected, high-risk clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Thank you for that wonderful summary, Neeraj. Dr. Neeraj Agarwal: That wraps up our kidney cancer highlights. Any closing thoughts, Jeanny, before we conclude? Dr. Jeanny Aragon-Ching: It's been so wonderful reviewing these abstracts with you, Neeraj. So, the 2025 ASCO Annual Meeting showcased a lot of transformative data across GU cancers, from first-in-class bispecifics to long-term survival in RCC. And these findings are already shaping our clinical practices. Dr. Neeraj Agarwal: I agree. And we have covered a broad spectrum of innovations in GU cancers with strong clinical relevance.  So, thank you, Jeanny, for joining me today and sharing your insights.  And thank you to our listeners for joining us. You will find links to the abstracts discussed today in the transcript of this episode. If you find these conversations valuable, please take a moment to rate, review, and subscribe to the ASCO Daily News Podcast wherever you listen. Thank you so much. 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. Neeraj Agarwal     @neerajaiims     Dr. Jeanny Aragon-Ching   Follow ASCO on social media:       @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn       Disclosures:   Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas  Dr. Jeanny Aragon-Ching:   Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono   Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,    Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics

The Rose’s Roxann Hayford sits down with Amy Byer Shainman, also known as BRCA Responder, to discuss her passion for patient advocacy and her award-winning work as the author of “Resurrection Lily” and film producer of “Pink & Blue Colors of Hereditary Cancer” and the soon to be released film, “Love, Danielle.” She opens up about her sister’s cancer diagnosis, the missed opportunities for genetic counseling, and the ripple effects of discovering a BRCA mutation. Amy shares the emotional weight of learning you’re at higher risk, the confusion over what to do next, and the importance of certified genetic counselors. With her latest film, “Love, Danielle,” she and the entire production team, cast, and crew aim to break the silence around hereditary cancer risk with honesty and humor. Connect with Amy Byer Shainman: Website: lovedaniellefilm.com Social: @BRCAResponder Book: "Resurrection Lily" Support The Rose HERE. Subscribe to Let’s Talk About Your Breasts on Apple Podcasts, Spotify, iHeart, and wherever you get your podcasts. Key Questions Answered What are BRCA1 and BRCA2 genes, and why do mutations in them matter? Which cancers are linked to BRCA mutations for both women and men? How are BRCA mutations inherited within families? Does having a BRCA mutation mean you will definitely get cancer? When should someone consider genetic testing for hereditary cancer risk? What is the role of a certified genetic counselor in this process? Are direct-to-consumer genetic tests reliable for assessing cancer risk? What are the main barriers people face when considering genetic testing? How can someone prepare emotionally for the possibility of life-changing test results? Why was the film "Love, Danielle" made, and what conversations does it hope to spark? Timestamped Overview 01:35 – Roxann welcomes Amy and sets the stage for a conversation about genetic risk and advocacy. 02:15 – Amy shares her personal journey: her sister’s diagnosis, frustration with missed genetic counseling, and the start of her advocacy. 03:37 – What are BRCA genes? Amy explains how these genes work and why mutations increase cancer risk. 04:50 – The conversation shifts to the specific cancers linked to BRCA mutations, for both women and men. 05:25 – Confusion about screening and testing: When should you get a mammogram? What guidelines exist for genetic testing? 06:42 – The importance of certified genetic counselors and why primary care doctors might not be enough. 08:14 – Direct-to-consumer tests versus medical-grade testing. How to find a qualified genetic counselor. 10:26 – The pitfalls of relying solely on your regular doctor for genetic risk assessment. 11:30 – Preparing for genetic testing: managing anxiety, seeking support, and understanding your choices. 13:57 – Barriers to testing: cost, access, and the hidden fears that keep people from seeking answers. 16:17 – The power of support groups like BRCA Sisterhood and the importance of safe, private spaces. 17:34 – Amy introduces "Love, Danielle," a film about hereditary cancer risk, family, and tough decisions. 19:37 – The challenge of making a movie about cancer that’s both honest and watchable. 21:06 – How the cast and crew’s personal cancer stories shaped the film. 22:18 – Amy reflects on separating her own experience from the film’s narrative. 25:04 – The differences between Amy’s real-life choices and those faced by the film’s lead character. 26:01 – The emotional reality: fear, family, and the weight of life-changing decisions. 27:34 – The unique risks of ovarian cancer for BRCA1 carriers and the lack of reliable screening. 28:25 – Amy’s children, their awareness of her advocacy, and their contributions to the film. 29:41 – Plans for the film’s release and how listeners can follow updates. 30:27 – The risks BRCA mutations pose for men, and which populations are most affected.See omnystudio.com/listener for privacy information.

Love the episode? Send us a text!In this episode of Breast Cancer Conversations, I, Laura Carfing, founder of survivingbreastcancer.org, delve into the critical topic of fertility preservation and genetic counseling for breast cancer patients. Joined by Alejandra Bernal, a genetic counseling student at the University of Pittsburgh, and Melissa Bourdius , a hereditary cancer counselor, we explore the intersection of cancer treatment, fertility, and genetics.Alejandra shares insights from her research on how patients are informed about the risk of infertility due to cancer treatments and the role genetic counselors can play in this process. She highlights the importance of asking the right questions and involving a multidisciplinary team to ensure patients receive comprehensive information about their options.Melissa discusses the genetic aspects of cancer, explaining how mutations in genes like BRCA1 and BRCA2 can increase cancer risk and affect family planning decisions. She emphasizes the importance of genetic counseling in helping patients understand their risks and make informed decisions about their treatment and future family planning.It's all here for you in today's episode! Resources:https://www.facingourrisk.org/support/insurance-paying-for-care/screening-and-prevention/fertility-preservation/overviewhttps://www.allianceforfertilitypreservation.org/fertility-risks-from-treatment/https://www.thechickmission.org/  Information about grants and advocacyhttps://worththewaitcharity.com/resources/patient-education/   Has practical patient resourcesSURVIVINGBREASTCANCER.ORGAttend a free virtual SurvivingBreastCancer.org event:https://www.survivingbreastcancer.org/eventsFollow us on InstagramSurvivingBreastCancer.org: https://www.survivingbreastcancer.org/Breast Cancer Conversations: https://www.instagram.com/breastcancerconversations/About SurvivingBreastCancer.org: SurvivingBreastCancer.org, Inc. (SBC) is a federally recognized 501(c)(3) non-profit virtual platform headquartered in Boston with a national and global reach. Through education, community, and resources, SurvivingBreastCancer.org supports women and men going through breast cancer. We provide a sanctuary of strength, compassion, and empowerment, where those diagnosed with cancer unite to share their stories, learn invaluable coping strategies to manage wellness and mental health, and find solace in the unbreakable bond that fuels hope, resilience, and the courage to conquer adversity.Support the show

Send us a textGot it From My Momma heads to the heart of New York City for a powerful and deeply personal conversation inside the Fox News headquarters. Host Jennifer Vickery Smith sits down with Kayleigh McEnany—former White House Press Secretary and current co-host of Outnumbered on Fox News—for the first installment in a special series focused on faith and family.In this compelling episode, Kayleigh opens up about her journey through motherhood, the values that ground her, and her time working closely with President Donald Trump. She also shares the emotional and courageous decision to undergo a preventative double mastectomy after testing positive for the BRCA2 gene—a choice rooted in strength, love, and faith.This inspiring conversation offers a glimpse into the moments that have defined her most.PRESENTED BY HEROES BEAUTY - LOOK GOOD. FEEL GOOD. DO GOOD. www.heroesbeauty.com MOMMA20 for 20% off your purchase of clean, conscious cosmetics and beauty care! COAT DEFENSEwww.coatdefense.comMOMMA15 for 15% off BAREFACED SKINCAREwww.barefaced.comMOMMA15 for 15% off www.gotitfrommymomma.tvThank you to our generous Got It From My Momma podcast friends! This episode is brought to you by: HARPER COLLINS CHRISTIAN PUBLISHING DEVOTIONS BOOKS - Grace for the Moment for Moms & Jesus Calling for Moms https://amzn.to/3DQ8GWL SUITSHOP PROM https://shrsl.com/4utgu WEDDING GROUP https://shrsl.com/4utgw CODE: GIFMM for a free tie! BAREFACED SKINCAREwww.barefaced.comUse MOMMA15 for 15% off your first purchase! TEXT a Skincare Specialist at 25169 for complimentary consults and to answer any skin questions.COAT DEFENSEwww.coatdefense.comInstagram @coat_defenseUse MOMMA15 for 15% off Got it From My Momma on the WEBwww.gotitfrommymomma.tv(Become an Insider!)Host- Jennifer Vickery Smith@jvickerysmith on Instagram WATCH podcast episodes on YouTube @gotitfrommymommapodcast

Just before her 38th birthday, Lauren Yerkes learned she had breast cancer. Genetic testing would reveal she had the BRCA2 inherited gene mutation that made her at higher risk of developing breast and ovarian cancers. Her experience made her want to educate people about inherited genetic mutations because she had no idea at the time that she was at risk. Lauren is here today to share her story, the preventative measures she has taken for her health and how she is giving back to the breast cancer community.

Many people believe that breast cancer is primarily caused by genetics, but did you know that only 5-10% of cases are linked to inherited mutations like BRCA1, BRCA2, and CHEK2? The truth is, your overall health and risk of recurrence are influenced by key biological processes such as detoxification, methylation, and inflammation—and these are things you can actively support with your nutrition and lifestyle choices. In this episode of Better Than Before Breast Cancer, I break down how these processes impact your health, how to recognize the signs of imbalance in your body, and why a low-carbohydrate diet can be a powerful tool in regulating glucose, insulin, and inflammation. I also explain why nutrition isn't about restriction—it's about giving your body the support it needs to function at its best. You'll learn:✔️ Why genetics are only part of the breast cancer risk equation✔️ How detoxification, methylation, and inflammation work together to protect your body✔️ Common signs that these processes may not be working efficiently✔️ How blood sugar regulation impacts detox, inflammation, and cancer risk✔️ How a low-carb, nutrient-dense diet supports healing and reduces recurrence risk✔️ Simple, actionable steps to support your body's detox, inflammation, and methylation pathways This episode will empower you to understand your unique genetic blueprint and how to make lifestyle changes that align with your body's needs. It's not about fear—it's about taking control of your health and making choices that truly support healing. Resources & Links:

We all know mitochondria is “the powerhouse of the cell” thanks to middle school science class, but when does that mean when we're talking about our overall health and longevity? In this episode, I dive into the fascinating world of mitochondrial health with Dr. Steven Gundry and Dr. Andrew Salzman. We discuss how optimizing mitochondrial function through diet, exercise, and light exposure can dramatically improve your health and energy levels. Plus, we explore the impacts of chronic inflammation, leaky gut, and environmental toxins on our mitochondria and overall well-being. View Show Notes From This Episode Get Free Weekly Health Tips from Dr. Hyman Sign Up for Dr. Hyman's Weekly Longevity Journal Full-length episodes of these interviews can be found here: 4 Non-Negotiables To Boost Energy And Optimize Your Mitochondria Sick And Tired Of Being Sick And Tired? How To Reclaim Your Energy How Supplementing With NMN Can Increase NAD levels, Energy, Reduce Inflammation, And Improve Insulin Resistance After a distinguished surgical career as a professor and chairman of cardiothoracic surgery at Loma Linda University, Dr. Gundry changed his focus to curing modern diseases via dietary changes. He is the author of New York Times bestseller The Plant Paradox, The Plant Paradox Cookbook, The Plant Paradox Quick & Easy,andThe Longevity Paradox,along with national bestsellersThe Plant Paradox Family Cookbook, The Energy Paradox,Dr. Gundry's DietEvolution,andUnlocking the Keto Code, and has had more than three hundred articles published in peer-reviewed journals on using diet and supplements to eliminate heart disease, diabetes, autoimmune disease, and multiple other diseases. He just released his latest book,Gut Check: Unleash the Power of Your Microbiome to Reverse Disease and Transform Your Mental, Physical, and Emotional Health. Dr. Andrew Salzman is a physician, inventor, professor, and biomedical entrepreneur. Dr. Salzman received his medical degree from Harvard University and has spent decades in drug discovery and development, raising over $165M in NIH grants for research. In addition to 50 patents, Dr. Salzman is credited with a breakthrough discovery in cellular DNA repair, which led to the world's first clinical application for successfully treating breast cancer caused by mutations in BRCA1 and BRCA2 genes. Millions of patients are benefiting from discoveries by Dr. Salzman in areas including mitochondrial health, gastrointestinal microbiota, damage caused by inflammation and oxidative stress to human cells and DNA, autoimmune disease, and cancer. This episode is brought to you by Pendulum, Cozy Earth, and SleepMe. Pendulum is offering listeners 20% off their first membership order at pendulumlife.com/farmacy. Discount applied at checkout. Right now, you can save 40% when you upgrade to Cozy Earth sheets. Just head over to CozyEarth.com. Customize your sleep with ChiliPad. Visit sleep.me/DRHYMAN and save up to $315 with code DRHYMAN. Learn more about your ad choices. Visit megaphone.fm/adchoices