Podcasts about oncotype dx

Bienvenidos a este podcast donde se abordarán los temas de mayor interés en el ámbito oncológico para Latinoamérica. A lo largo de este proyecto los Dres. Diego Ballén y Mauricio Lema, oncólogos clínicos colombianos, entrevistarán a un invitado especial para abordar con base en evidencia científica y a su experiencia a aquellas interrogantes que llegan a surgir diariamente en la práctica clínica.Durante este episodio el Dr. Carlos Alberto Vargas, oncólogo clínico adscrito al CETIC, la Fundación Santa Fe y la Clínica del Country en Bogotá, Colombia, discutió en conjunto con nuestros coordinadores sobre el tratamiento del cáncer de mama.Con base en su experiencia, el Dr. Vargas respondió a las siguientes interrogantes:¿Cuál es el impacto clínico del estudio PATINA y qué tan aplicable es en la práctica inmediata?¿Qué aspectos deben considerarse sobre la toxicidad de palbociclib en combinación con doble bloqueo HER2?Si no existieran restricciones regulatorias, ¿es razonable adoptar la estrategia propuesta por PATINA en pacientes con enfermedad triple positiva?¿Cómo influye el análisis actualizado de Oncotype DX presentado en San Antonio en la decisión de uso de antraciclinas o taxanos?¿Qué valor tienen los resultados del estudio INSEMA respecto a la omisión del ganglio centinela en pacientes seleccionadas?¿Cómo aplicaría el protocolo del INSEMA en pacientes premenopáusicas?¿Qué limitaciones existen en la calidad de la ecografía axilar como herramienta de estadificación en la práctica clínica local?Según el consenso de St. Gallen, ¿cuál es el papel actual de los inhibidores CDK4/6 en adyuvancia a partir de los estudios monarchE y NATALEE?¿Qué relevancia tiene el análisis preliminar del estudio KEYNOTE-756 y cómo se posiciona la inmunoterapia neoadyuvante en pacientes luminales B con baja expresión hormonal?¿Cuáles son las controversias actuales en torno al tratamiento adyuvante con inmunoterapia en pacientes con cáncer de mama triple negativo y tumores pequeños tratados con cirugía inicial? Referencia:Este contenido se basa en la interpretación crítica de la evidencia científica disponible, así como en la experiencia clínica del o los ponentes como profesionales de la salud en instituciones de referencia.Para profundizar en los conceptos discutidos, se recomienda al profesional de la salud consultar literatura científica vigente, guías clínicas internacionales y la normatividad aplicable en su país. Fecha de grabación: 19 de marzo de 2025.Material exclusivo para profesionales de la salud. Este material ha sido desarrollado únicamente con fines educativos e informativos y no tiene la intención de sustituir el juicio clínico de los profesionales de la salud.Las opiniones y declaraciones presentadas en este contenido son responsabilidad exclusiva de los ponentes y no reflejan necesariamente la postura institucional de ScienceLink ni de terceros mencionados. La información presentada se basa en el conocimiento y la experiencia profesional de los ponentes. La veracidad, exactitud y actualidad científica de los datos son de su exclusiva responsabilidad. Así mismo garantizan que el contenido utilizado no infringe derechos de autor de terceros y asumen toda responsabilidad por su uso.Se deberán de revisar las indicaciones aprobadas en el país con estricto apego al marco regulatorio aplicable para cada uno de los tratamientos y medicamentos comentados.

Our final breast cancer episode is here! Today, we are talking about the role of Gene Expression Assays in early hormone receptor-positive breast cancer management. The specific questions we asked included when we can de-escalate and for which cohort of patients these assays can be used. There's lots more to this episode, but we explore the role of Oncotype Dx!Studies discussed in the episode:TAILORxRxPonderFor more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.

Susan Svoboda was accustomed to going in for her mammogram every November.  She enjoyed a healthy lifestyle, which included running 65 half marathons.  But in late 2021, after her mammogram, she was called to return to the doctor's office.  After scans and a biopsy, she was diagnosed with Stage 1-2 invasive ductal carcinoma.   Given her healthy routine, Susan was shocked, but she quickly had to turn her attention to her treatment.  In 2022, she underwent a successful lumpectomy.  Because of the location of the lump, and her low Oncotype DX score, the oncologist told Susan she would not have to undergo chemotherapy.  Instead, she would need to get radiation treatment, 15 rounds over three weeks; but her oncologist also suggested her regimen include estrogen inhibitor pills for the next five years.   Susan consulted reading materials and talked to numerous women who had tried the pills.  All of them had something to say that helped her to make the difficult decision to refuse the estrogen inhibitors.   Susan Svoboda found her way to survivorship.  She says that while she doesn't do half marathons, she still some light running and goes walking every day. Her journey inspired her to spend 2022 writing a book, “I Hate The Color Pink.”  She says the satisfaction that comes from writing the book is its spreading a message of information and hope.   By way of advise, Susan advises women to get their mammograms and when dealing with doctors to ask questions, lots of questions.   Addition Resources:   Susan Book, available on Amazon: “I Hate The Color Pink”

Dr. Shannon Westin and her guest, Dr. Reshma Jagsi, discuss the paper "Omission of Radiotherapy After Breast-Conserving Surgery for Women With Breast Cancer With Low Clinical and Genomic Risk: 5-Year Outcomes of IDEA" recently published in the JCO. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we get in depth with manuscripts that were published in the Journal of Clinical Oncology. I am your host, Shannon Westin, GYN Oncologist and Social Media Editor for the JCO. It is my pleasure to speak with Dr. Reshma Jagsi. Hello, Dr. Jagsi. Dr. Reshma Jagsi: Hello. Thanks for having me. Shannon Westin: I am so excited that you're here. Dr. Jagsi is the Lawrence W. Davis Professor and Chair of the Department of Radiation Oncology at Emory University School of Medicine, Winship Cancer Institute. She is going to be talking about her incredible work, "The Omission of Radiotherapy After Breast Conserving Surgery for Women with Breast Cancer with Low Clinical and Genomic Risk: Five-year Outcomes of IDEA," which was published in JCO in February 2024.  All right, let's get right to it. First, I want to levelset. Can you run us through some brief facts and figures about breast cancer just to make sure that all the listeners are on the same page?  Dr. Reshma Jagsi: Breast cancer is the most common cancer in the world. It's 12.5% of all new annual cancer cases worldwide and is the most commonly diagnosed cancer among US women. About a third of all newly diagnosed cancers in women are breast cancer, and about 13% of US women develop invasive breast cancer over their lifetime. In 2023, there were nearly 300,000 new cases of invasive breast cancer. The median age of breast cancer diagnosis is 62, meaning an awful lot of people are getting diagnosed with breast cancer in the population that we specifically chose to study.  Shannon Westin: Wow, you're really good at this. That's like the perfect transition to move to the next piece. So, first, I think I'd love to hear about the standard of care for the population that you were studying and how we got to this point.  Dr. Reshma Jagsi: We offer women who are diagnosed with early-stage invasive breast cancer the option of breast conservation, and we encourage breast conservation because, of course, it is a better-tolerated surgery than mastectomy. Many women are eligible for breast-conserving therapy. And years ago, we as radiation oncologists encouraged our surgical colleagues to refer to breast-conserving therapy as lumpectomy plus radiation, just as one set. Because the studies that have been done in the 1970s and 1980s to establish that breast conversation was equally safe and effective in treating breast cancer relied on radiation therapy to minimize in-breast tumor recurrence rate, which one of those trials independently showed that there was no difference in survival. But the ones that compared lumpectomy surgery alone to lumpectomy followed by radiation therapy did show a pretty substantial improvement in local control with the addition of radiation treatment. And so radiation treatment became a part of a parcel of breast conservation in the early 1990s when consensus statements came out favoring breast conservation as a treatment approach.  And so the net analysis has combined all of these studies together and showed that overall, without radiation treatment, a patient treatment with a lumpectomy had a 30% risk of in-breast tumor occurrence in those historical studies. And it was reduced by about two thirds to about 10% when that lumpectomy was followed by radiation in those historical randomized trials. But of course, we've made many advances in our understanding since that time, and so that's what this study is seeking to build on. Shannon Westin: It makes sense. We all know that radiotherapy can lead to other issues, acute and chronic morbidities, as well as cost and having to do the treatment itself. So we're all interested in de-escalation of therapy. Tell me, prior to your study, what data were out there potentially supporting the de-escalation and avoiding radiotherapy in that specific population? Dr. Reshma Jagsi: In the ‘90s, after those landmark foundational historical trials have been completed, there was a lot of interest in seeing if we could identify a population of patients in whom the risk of local recurrence was sufficiently low that they might safely choose to omit radiation therapy. All of these randomized trials have shown very consistently that there is a relative risk reduction. Whatever your risk is without radiation, radiation reduces that risk. The overall disease recurrence risk is cut in half with the addition of radiation treatment. But, if I told you that your overall risk was 1%, and I could cut that in half with radiation, you might say, “I might be willing to tolerate the 1%.” At least some women might be willing to tolerate that. So can we find a population in whom the risk is low enough that at least some of those women say, "Look, I want to go without radiation." And of course, the balance of where that number should be changes as we get better and better at delivering radiation. So you mentioned, radiation comes with toxicity, comes with burden and yet, there have been some tremendous advances, and particularly in recent years, to shorten the course of radiation. We have evidence that we can treat partial breast radiation safely in five treatment fractions. We have five-year data that we can treat the whole breast in five-treatment fraction. We certainly have long term evidence that we can the whole breast with 15 fractions from many patients diagnosed with breast cancer. So the burden has decreased. We've also found that with hypo fractionated shorter courses of radiation, the toxicities are much lower, patients tend to tolerate radiation treatment both in terms of acute side effects and long term side effects extremely well.  So that balance of what is low enough is changing with time.  But the trials that were started in the 1990s included the CALGB 9343 trial, a landmark trial published in the New England Journal of Medicine, with its five-year results showing only a 4% risk of recurrence at five years in patients who were 70 or older with clinical stage one disease that was hormone receptor-positive if they received a lumpectomy and tamoxifen alone, not receiving radiation - that risk, if we added radiation in this randomized trial, was only 1%. So there was still a substantial relative risk reduction with radiation treatment. This was published in 2004 in the New England Journal of Medicine.  At the same time, there was a Canadian trial that was published, and in that trial that included women who were 50 years of age and older, there were more concerning results with, even in a very favorable prespecified subgroup of patients who had node-negative breast cancer and T1 hormone receptor-positive tumors, the risk of ipsilateral breast tumor recurrence was 15% at eight years. So that started to feel excessive for women 50 and older.  Meanwhile, we went on to get the update of the CALGB trial, and the 10 -year results showed that the risk was, in the women 70 and older, was only about 10% without radiation. It was 2% with radiation. So again, there was a benefit from radiation, and it's up to each individual woman to decide whether they'd prefer to proceed and minimize their risk, or would be willing to tolerate something like a 10% risk. More recently, just this past year in the New England Journal, the PRIME 2 study from the United Kingdom, looking at women 65 and older, again, early-stage node-negative hormone receptor-positive tumors, and very similar results - 10% versus 1% local control at 10 years.   So you get an improvement with radiation. But there are some women who are 65 or 70 and older who say, I'm willing to tolerate the 10% risk. And so the question was, could we identify some patients who are younger than 65 to 70, but still postmenopausal, like in that Canadian trial, who might actually have similar outcomes - low risks at five and ten years - such that they might want to entertain the option of omitting radiation therapy, which right now is not standard or in any guidelines? So we have some promising information from some retrospective analysis of that Canadian trial that suggested that looking at biology might help. And in fact, the LUMINA trial, published just this year from Canada, did a prospective cohort study selecting patients based on immunohistochemistry, and suggested very low risks, five years in patients who were somewhat younger, although it ended up that the median age of the patients in that study was 67. So we still sort of had this question of what about the younger postmenopausal patients? And that's what took us to IDEA.  Shannon Westin: And just for my education and for the education of the listeners, when you have an in-breast recurrence, how likely are you to be able to cure that? Is that tough to cure, or can you usually get control again? Dr. Reshma Jagsi: It's an excellent question. And so often these recurrences are caught early and are still completely curable with additional intervention. Now, there can be an impact, of course. You can talk to any survivor about the devastating impact of being diagnosed with breast cancer recurrence, and no one wants to go through that. And so there are reasons that people will want to reduce that, and there are implications for breast conservation because it may be that the remaining breast tissue is insufficient to allow a second breast conserving surgical procedure. It may also be that when one experiences recurrence, one decides, "I'm done with this. I'm having a mastectomy at this point." So, in-breast recurrences are very meaningful to patients and something that we should not take lightly. Shannon Westin: It seems, though, the majority of the studies that you were talking about, aside from the LUMINA study, were predominantly based on those clinical features like stage and things like that. So, can you talk a little bit about the role of molecular features, genomic testing, things like that, to select patients?  Dr. Reshma Jagsi: Yeah. So, we have seen a tremendous change in the way we think about breast cancer in recent years, with a real focus on tumor biology, rather than classic clinical pathologic features alone to help us make decisions about systemic therapy. And so, there is a body of work that suggests that genomic assays, including the 21-gene recurrence score, that's commonly used for treatment decision making already ordered in many of these patients and available to us, that it may be useful in understanding patients' risk of local recurrence, both when they are treated with radiation and when they are treated without radiation. So, Terry Mamounas did some wonderful work looking at NSABP data where you know that the mastectomy patients at the time of the studies that were included were not receiving radiation treatment. And it did appear that the 21-gene recurrence score was helping to discriminate for local regional recurrence risk, suggesting it might be useful to use that to select patients who might be at lower risk.   Shannon Westin: All right, perfect. So, that leads us to your study. So, let's talk a little bit about the design and the population and kind of how you put it together.  Dr. Reshma Jagsi: This was really a true collaboration, a partnership across multiple 13 collaborating sites, where my colleagues, the lead investigators at each site, were extremely committed to this question. And we sought to do a preliminary cohort trial, really involving 200 patients. And over the course of three years, we enrolled those 200 patients who were aged 50 to 69 years old and had unicentric invasive breast cancer and lumpectomy surgery that led to negative margins of 2 mm or greater. And their disease needed to be PR positive, HER2 negative, it needed to be node negative, pathologically node negative, and the Oncotype DX 21-gene recurrence score needed to be less than or equal to 18. And then these patients were offered the opportunity to consent and register on a trial to receive five years of endocrine therapy as standard of care alone, and 10 years of surveillance on study, or to proceed with the standard of care treatment off trial, which would have been a recommendation to receive radiation treatment. And so, we ended up with patients with a mean age of 62 years, which, as I said, that's really more mapping the overall population of patients in the country. And we were able to report our results at the San Antonio Breast Cancer Symposium and with simultaneous publication in JCO, with a median follow up of 5.2 years. Shannon Westin: Okay, and let's talk about a little bit about your major findings. Tell us what your good work demonstrated. Dr. Reshma Jagsi: So, the overall and breast cancer-specific survival rates at five years were both 100%, and the five-year freedom from any recurrence was 99%, with a 95% confidence interval that went from 96% to 100%. But I want to emphasize that these are five-year data in a younger postmenopausal population, where five-year data are not typically sufficient to guide decision making. So, I really want to emphasize that these are very early results. But really, what happened here was we only had a couple of patients who had recurrences before five years, two patients, and that was one isolated ipsilateral axillary recurrence, and one ipsilateral breast event. But we also did see six additional patients who recurred later than five years after breast conserving surgery. And because we don't have much long-term follow-up, it makes it incredibly important for us to continue to follow this cohort over time before people make any Monday morning practice implications of offering this cohort of patients, or patients like this cohort of patients, omission off trial.  The good news is that there are ongoing trials that are building on this work, including NRG-BR007, the DEBRA ,that includes a population of patients really similar to those enrolled on IDEA and randomizes them to radiation or no radiation, which is actually incredibly important. Because what we want to understand is also the quality of life effects of omitting radiation therapy because what we don't want is to inadvertently cause an increase in worry about recurrence. Or, you could imagine that patients who omit radiation treatment then feel really stuck with their endocrine therapy. Now, endocrine therapy is the standard of care, but if they're experiencing terrible endocrine therapy side effects and they didn't get radiation treatment, are they more likely to persist with that endocrine therapy and to be miserable because they omitted a treatment that, as I mentioned earlier, can be administered now in five days or less?  And one of the questions that keeps coming up from older patients that I treat, where we already offer the option of omitting radiation, those CALGB and PRIME II patients, those patients will often say to me, "I've got to say, Doc, that whole experience of radiation that you described for five days, and the toxicity, and that doesn't sound so bad to me. What sounds bad to me is multiple years of endocrine therapy." And so, there are also ongoing trials in Europe, and I hope one day in the United States, also looking at older women and offering them a de-escalation of a different sort. Now that we have made so many advances in radiation treatment, maybe the optimal monotherapy for an older adult is actually, for many patients, given their values and preferences, going to involve omission of endocrine therapy. And we need to find out if that's safe. And again, Europa in Europe is investigating that question, and I hope that the American cooperative groups take up something similar. Shannon Westin: That's awesome! And what else is going on in this space? Any other trials? That was like, such a great review of ongoing trials, and I'm sure our listeners would love to have your expertise. Anything else that you're looking forward to that might impact the treatment landscape here? Dr. Reshma Jagsi: Absolutely, and if there are listeners in other parts of the world, there are trials going on also looking at this. There is PRIMETIME, which is a cohort study designed, but with a much larger cohort that's going on in the United Kingdom. There's the EXPERT trial that is randomizing patients to radiation treatment or not in Australia and New Zealand. So, there are many trials that are ongoing, again, looking at de-escalation of radiation therapy. And I want us all, regardless of our specialty, to think about ways that we can de-escalate and optimize the options that are offered to our patients. And I think there's a tendency for patients to be very scared of radiation, sometimes, for our colleagues to be very scared of radiation. I mean, we are the only specialty that has a special “danger radiation sign” that comes to mind when you hear the word radiation therapy. So, it can be this very frightening thing that we often leap to efforts to avoid.  And what I don't want to be the conclusion of this is, “Isn't it great? Radiation oncologists themselves recognize that radiation is terrible and that you should avoid it.” That's not the case. What I hope people will say is, “Isn't it great that radiation therapists are trying to offer as many options to patients as possible?” Because it means a lot to a patient who's had the sense of power and control and autonomy ripped away from them by a breast cancer diagnosis, to be given many options to articulate their values and their preferences and to decide what treatment makes most sense for them. I think, for a lot of patients, that involves radiation treatment. And I think what we need to do as physicians is think about what other things are our patients really concerned about.   Our medical oncology colleagues have done tremendous work to de-escalate systemic therapy in the form of chemotherapy. Our colleagues in surgery have, again, de-escalated mastectomies, axillary dissection. So, there are these ongoing efforts, and I do honestly believe that the next frontier is endocrine therapy and optimization of endocrine therapy. It is so powerful. It is why we have such wonderful outcomes. We know that we should have a healthy respect for ER-positive cancer, which can recur in the long term. We don't want to throw out the baby with the bathwater, but baby steps towards understanding what happens if we peel back our treatments is our obligation.  Shannon Westin: I think this is a perfect place to end/ I agree - less is more is really becoming a resonant statement across all of our different subtypes. We're certainly seeing it in GYN oncology, and just like you said, systemically or even surgically. So I agree. I think we have a call to action to really assess what we've always done and make sure that we're not over-treating patients for whom it's inappropriate.  So I think this is great. And I just want to commend you again on your work. These types of multicenter trials are really hard to do, and getting it done in such a short period of time and really getting the data out to patients is so important. And I appreciate what you're saying about needing more follow-up, but it is certainly very reassuring and very in line with what we've seen. So congratulations on your work. Dr. Reshma Jagsi: Thank you. And I just again want to thank all the patients who enrolled, the Coleman Foundation for their support, the University of Michigan for doing the multi-site coordination and the biostatistic support, and all of the collaborating investigators. I mean, this was a labor of love for everyone involved. Shannon Westin: Yeah, these types of trials definitely take a village. Well, great work. Thank you for taking the time. I know how busy you are. So again, we are so honored and so excited to talk about "The Omission of Radiotherapy After Breast Conserving Surgery for Women with Breast Cancer with Low Clinical and Genomic Risk: Five-year Outcomes of IDEA,” just published in print, February 2024 in the JCO. Definitely check it out. And please check out our other episodes of JCO After Hours. We'd love to have your feedback. Take care. The purpose of this podcast is to educate and 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. Jagsi: Stock and Other Ownership Interests Company name: Equity Quotient Research Funding Company name: Genentech"

*** Diese Folge wurde mit freundlicher Unterstützung der Firma Exact Science Deutschaland GmbH produziert *** https://www.exactsciences.com/de   Anregungen, Kritik: sven.perner1972@googlemail.com christiane.kuempers@uksh.de

Lajos Pusztai, MD, and Robert Figlin, MD, discuss the practicality of neoadjuvant I-O as demonstrated in KEYNOTE-522 and the application of the Oncotype DX 21-gene signature test in the RxPONDER study, both presented at the 2021 San Antonio Breast Cancer Symposium.

Did you know that you have choices when it comes to treating your cancer? You CAN be in charge of your health and have the personalized care you want! My guest this week, Stacey Tinianov, is a mom, caregiver, and stage 0 breast cancer survivor. When she received her diagnosis at only 40 years old, she knew the standard of care was not for her, and she has a message to share for anyone else who feels the same. In this episode, Stacey dives into the challenge of rejecting a standard of care, what treatment path she chose instead, and her TOP TIPS to be better prepared if cancer finds its way into your life.  We're exploring:  What it meant for her to have breast cancer at the same time as her mom Why Stacey advocated for the Oncotype DX™ test—and what it revealed Some SURPRISING statistics about Tamoxifen How to achieve personalized care and engage with the healthcare system What you might not know about obesity & breast cancer The #1 way we spoke up about drug side effects (this is SO important!) And so much more! Join me for a Coffee Chat here: https://fitnessdesignsolutions.as.me/CoffeeChat Follow me on Instagram to get the latest updates on the podcast: https://www.instagram.com/thejennifercochran/ Continue the conversation in my free private Facebook group, Surviving is JUST the Beginning: https://www.facebook.com/groups/SurvivingisJUSTtheBeginning/

I am not an author by trade, actually, my purpose is to educate and entertain children. There are people that are truly authors and they live by their pen. While I always thought I would write my life story one day, I never perceived that I would write books for Children. The twists in your life, really determine some of the journeys that you take. My forks in the road are Sarcoidosis and Breast Cancer. Sarcoidosis is an auto-immune disease that can attack a person's joints, eyes, lungs, heart, and other organs. It does not have a cure and has taken the lives of two very famous people most of us know. One is comedian Bernie Mack and the others NFL Football Star Reggie White. The Sarcoidosis I have attacks my lungs and joints. I was diagnosed with this life twist in 2011. Not being able to breathe gives you, perspective and someone telling you that you have a terminal disease can be mentally devastating if you don't have strong faith. It (The Sarcoidosis) stopped me momentarily but did not keep me down. I went back to working 60 to 70 hours per week and to what most people would consider a normal life. My Mom became deathly ill in 2013, a bowel prolapse that became gangrene. I was working and going back and forth to help with her care. I had a serious accident that year. I fell asleep behind the wheel of the van I was driving, but I made it through again. My Mom though made the transition on my brother's birthday in November of that year. She told me that she was ready, so my mind was at ease and her death did not hurt me as much as I thought it would. I found a lump in my right breast in May of 2014. I was not alarmed, because I had a scare before, due to a lump I found in my left breast in 1988. The surgeon removed 27 small benign cysts then. So, in my mind, I thought it was just a cyst, but I kept my eye on it. This thing that I thought was a benign cyst grew at an alarming rate from the size of a pea to the size of an egg in about 8 to 10 weeks. I went to see my doctor and we scheduled a mammogram. After the results came back, I went to have the lump biopsied. The surgeon told me, I regret to inform you, it is Breast Cancer. I was in shock, so much so, that I didn't even ask him what stage or grade. I just thanked him for the information and continued traveling to work. This new life twist, will I live or die? For a moment I died mentally. I woke up and started researching Breast Cancer. There are forty different types of BreastCancer. Wow! My oncologist, a wonderful doctor wanted me to start chemotherapy after the bi-lateral mastectomy surgery. She just didn't know that I had is not planned to take the Chemo. She told me; I give you five years to live without it. (Chemotherapy) Here is the kicker, the pathology report was inconclusive. I was thought to have triple-positive breast cancer.When I read the report, it said in small print at the bottom, this test is inconclusive. I went to my family Doctor and we read the report together and she confirmed that the report stated that that they did not know what kind of breast cancer I had. Meanwhile, my oncologist still was pressing Chemotherapy, again I said no, I wanted to have the Oncotype DX test to determine what type of breast cancer was in that tumor. She told me to take could take 6 to 8 weeks. I told her; we will just have to wait. (She just didn't get it; I really had decided I wasn't going to take the Chemo.) After the Oncotype DX testing, the results were; that I have ER+ Breast Cancer. This is an Estrogen receptive cancer. Again, she was insisting on Chemotherapy. She didn't know that I had been researching, about all the different types of breast cancer and the medications used to treat them. I declined the treatment; my family doctor was not happy with my decision. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/letssipandtalkwithfrema/message Support this podcast: https://anchor.fm/letssipandtalkwithfrema/support

In this episode, Javier Cortes, MD, PhD; Stephen R. D. Johnston, MA, FRCP, PhD; and Sara Tolaney, MD, MPH, answer questions from an  audience of healthcare professionals on topics related to leveraging CDK4/6 inhibitors for HR-positive/HER2-negative early breast cancer, including:Clinical role of Ki-67 testingCore biopsies for identifying potential benefit with neoadjuvant endocrine therapyCombining CDK4/6 inhibition with tamoxifenPresenters:Javier Cortes, MD, PhDHead, Breast Cancer ProgramIOB Institute of OncologyMadrid and Barcelona, SpainStephen R. D. Johnston, MA, FRCP, PhDProfessor of Breast Cancer MedicineBreast UnitDepartment of MedicineRoyal Marsden HospitalLondon, United KingdomSara Tolaney, MD, MPHAssistant Professor of MedicineHarvard Medical SchoolAssociate DirectorSusan F Smith Center for Women's CancerDirector of Clinical Trials, Breast Oncology  Director of Breast Immunotherapy  Clinical ResearchSenior PhysicianBreast Oncology ProgramDana-Farber Cancer InstituteBoston, Massachusetts, USAContent based on an online CME program supported by an educational grant from Lilly.Link to full program, including downloadable slides and associated Podcast Pearls PDF:https://bit.ly/37tfvtj

In this episode, Carly chats with Holistic Health Coach and breast cancer survivor, Stephanie Fletcher about her healing journey + how to best support a friend or loved one going through chemotherapy. This episode covers: - Stephanie's journey through diagnosis and treatment - How Stephanie blended traditional and holistic cancer treatments to form an integrative approach that worked for her - The importance of mindset in a healing journey - The holistic protocols Stephanie blended with chemotherapy to keep herself feeling well - What tools Stephanie recommends having with you during a chemo session, or as a gift for friends or loved ones attending chemo sessions - Ways to empower yourself as a patient - How Stephanie kept the negative side effects of chemotherapy treatments at bay using fasting, high-dose Vitamin C, mistletoe injections and more - Some of the possible contributing factors for Stephanie's breast cancer - The power of self-reflection in a healing journey - Information on the mammaprint, Oncotype DX, and circulating tumor cell tests + how they help diagnose cancer - How to best support a loved one going through chemotherapy Resources: The Health Haven– (San Antonio, TX) Certified Holistic Health Coach Namaste Health Center– (Durango, CO) Dr. Stacy Mulkey, ND The Breast Center– (New Orleans, LA) @HealthHavenCoach The Daily Detox 8-week course Connect: IG: @carlyloveskale web: carlybrownwellness.com Stephanie earned her Bachelor of Arts in exercise science from Abilene Christian University in Abilene, TX. She spent 16 years helping employees in corporate America reach fitness and nutritional goals while leading personal and group training classes across South/Central Texas. She has also started two outdoor fitness companies in two countries. Currently residing in San Antonio, Texas, Stephanie holds a holistic health coach certification from The Institute of Integrative Nutrition.

Returning guest, Dr. Eric Klein, Chairman of the Glickman Urological and Kidney Institute at Cleveland Clinic discusses new 20-year outcomes from a development study of the Oncotype DX Genomic Prostate Score® (GPS) test that was recently published in JCO Precision Oncology (March 2021). The study highlights the role of the GPS test, the only genomic test for prostate cancer with 20-year outcomes, in assessing the risk of long-term distant metastases (DM) and prostate cancer-specific mortality (PCSM) for patients with localized prostate cancer. Eric A. Klein, MD, is the Chairman of the Glickman Urological & Kidney Institute and a staff member in the Taussig Cancer Institute at Cleveland Clinic. His clinical interests are cancers of the prostate, testis, and kidney. For several years, including the current edition, Dr. Klein is listed in Best Doctors in America. Board-certified in urology, Dr. Klein is a frequent lecturer and visiting professor at numerous national and international universities. He was the National Medical Study Coordinator for the National Cancer Institute-sponsored Selenium and Vitamin E Cancer Prevention Trial (SELECT). Dr. Klein is the editor of Urology and has been the recipient of numerous awards from the American Cancer Society, the University of Pittsburgh School of Medicine, and the Cleveland Clinic. Dr. Klein received his medical degree from the University of Pittsburgh School of Medicine in Pennsylvania. He completed his residency in urology at Cleveland Clinic and a fellowship in urology at the Memorial Sloan Kettering Cancer Center in New York. #GenomicProstateScoreTest #GPSTest

Returning guest and study author, Steve Shak, Chief Medical Officer at Exact Sciences discusses results presented at SABCS (San Antonio Breast Cancer Symposium) from the Phase 3 RxPONDER (Rx for Positive Node, Endocrine Responsive) study, one of the largest randomized, prospective clinical trials in women with node-positive, hormone receptor-positive (HR+), HER2- early-stage breast cancer. Dr. Steve Shak is the Chief Medical Officer for Exact Sciences. Joining the company in 2019 upon the closing of the Genomic Health / Exact Sciences combination, his key responsibilities include leading strategy for the company’s clinical development plans, building relationships with key leaders and institutions in the cancer community, and ensuring the voice of patients and physicians are heard at all levels of the organization. Before serving as Chief Medical Officer, he was the Co-Founder, Chief Medical Officer, and Chief Scientific Officer at Genomic Health, driving Oncotype DX assay development in breast, prostate and colon cancer. Before then, he was the Research Director and Staff Clinical Scientist at Genentech, leading the clinical team in the development of the targeted breast cancer drug Herceptin®, and the research team in the discovery of the cystic fibrosis drug Pulmozyme®. He also taught as an Assistant Professor of Medicine and Pharmacology at New York University School of Medicine. Dr. Shak received his medical degree from New York University School of Medicine and his formal post-doctoral training at Bellevue Hospital and the University of California, San Francisco. He has a bachelor’s degree from Amherst College in Massachusetts.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In this podcast, Cancer.Net Associate Editor Dr. Norah Lynn Henry discusses new research presented at the 2020 San Antonio Breast Cancer Symposium, held virtually December eighth through eleventh. Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. View Dr. Henry’s disclosures at Cancer.Net. ASCO would like to thank Dr. Henry for discussing this research. Dr. Henry: Hi. I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of updates from the 2020 virtual San Antonio Breast Cancer Symposium. My institution enrolled patients in the first trial that I will discuss, otherwise, I have no conflicts of interest for any of the trials that I will talk about. Today, I'm going to focus primarily on treatment of non-metastatic breast cancers that are hormone receptor-positive and HER2-negative. These studies highlight personalizing treatment for individual patients. In the first and last trials I will mention, the studies examine whether it is possible to give less treatment without substantially increasing the risk of breast cancer recurrence. In general, giving less treatment leads to fewer long-term toxicities and better quality of life. In contrast, the other 2 trials I will mention are examining adding more therapy to standard treatment with the goal of increasing breast cancer cure rates for patients at high risk of recurrence without causing too much additional toxicity. One of the biggest stories in this meeting was the result of the RxPONDER trial. This trial enrolled thousands of women with hormone receptor-positive, HER2-negative breast cancer, who had cancer present in 1 to 3 lymph nodes under her arm. The standard treatment for patients who have lymph node positive breast cancer has been to recommend chemotherapy in addition to anti-hormone therapy. This trial is testing whether that is actually the best treatment. In this trial, every patient's tumor was tested with a test called Oncotype DX and was given a recurrence score ranging from 0 to 100, depending on how quiet or aggressive the tumor is. Women whose tumors had a score between 0 and 25, which is at the low range, were randomized, like flipping a coin, to either receiving the standard, which is chemotherapy followed by anti-hormone therapy, or to just anti-hormone therapy alone. The patients were then monitored to see if they developed recurrence of their breast cancer. Overall, there was no difference between the groups. Meaning that adding chemotherapy to the treatment did not provide a benefit in terms of reducing risk of recurrence. When they divided the groups by lower or higher score, it still didn't make a difference. However, when they divided the women by menopausal status, it did. Women who were post-menopausal when they were diagnosed with breast cancer did not get any benefit from chemotherapy. In contrast, women who were pre-menopausal did get a benefit from chemotherapy. And in fact, they lived a little longer than those who only got anti-hormone therapy. However, there's still a question about how much of the benefit is from the chemotherapy itself acting directly on the cancer and how much is from the chemotherapy putting the ovaries to sleep, which also treats the cancer, although indirectly. Therefore, the take-home message for a post-menopausal woman with hormone receptor positive, HER2-negative breast cancer who has 1 to 3 involved lymph nodes, is to talk with her oncologist about whether her tumor should be tested to help make a decision about chemotherapy as opposed to just assuming that she needs chemotherapy because her lymph nodes have cancer in them. For pre-menopausal women, it's a little less clear, unfortunately. In that case, it is important to talk about the pros and cons of chemotherapy with her oncologist depending on her exact situation, including her age and the amount of cancer in the breasts and the lymph nodes. Hopefully, we will learn more about how best to treat pre-menopausal women when additional analyses are performed on the data from this trial. Also related to non-metastatic hormone receptor positive, HER2-negative breast cancer, updates on 2 trials related to the use of adjuvant CDK4/6 inhibitors on patients with high risk to breast cancer recurrence were presented. The CDK4/6 inhibitor medicines are routinely used to treat patients with metastatic breast cancer since the combination of these drugs plus anti-hormone therapy results in longer time to disease worsening compared to just anti-hormone therapy alone. Therefore, these drugs are now being tested in the non-metastatic setting to see if they increase the likelihood of cure of breast cancer. In the first trial called MonarchE, addition of abemaciclib, which is a CDK4/6 inhibitor, to standard aromatase inhibitor therapy decreased the likelihood of recurrence of invasive disease in patients at high risk of disease recurrence. However, the length of follow up of the patients who participated in the trial is still rather short, and so far, adding the treatment has not shown that people will actually live longer. The other trial that was presented, called PENELOPE-B, studied a similar CDK4/6 inhibitor medicine called palbociclib in a similar setting. In that trial, although the benefits looked promising early on, with longer follow up, the benefits have unfortunately disappeared. Therefore, although the results of MonarchE look very promising, we still need more follow up to determine the actual benefit to patients. Also importantly, this drug is not currently approved for treatment of early stage breast cancer at high risk of recurrence, and it is not currently included in treatment guidelines. So at this point, it is unlikely that the drug costs will be covered. We await additional updates from these and other trials of similar design in order to know whether patients should be receiving these drugs as part of their breast cancer treatment. And finally, to change gears a little to patients who are at low likelihood of disease recurrence, we also got an update of the PRIME II trial. This trial asked whether radiation therapy is beneficial in women over the age of 65 who have small lymph node-negative, hormone receptor-positive breast cancer. In this trial, most patients had tumors that were smaller than 2 centimeters, and all underwent lumpectomy and were planning to take adjuvant anti-hormone therapy. Patients were randomized either to receive radiation therapy or to not receive radiation therapy. Radiation therapy is the standard of care in this setting. Consistent with their earlier results, not having radiation therapy did increase the risk of local recurrence a little from 1% to 10% over 10 years. And this really highlights that although the risk of local recurrence in the breast is a bit higher if a patient does not have radiation therapy, it still has a 90% chance of not having a recurrence during that 10-year period. Also, not getting radiation did not affect survival from breast cancer. It is important to note that most patients likely took endocrine therapy, and it is thought that risk of recurrence is higher if both radiation therapy and endocrine therapy are omitted. Therefore, patients over the age of 65 or 70 who have small hormone receptor-positive breast cancers should talk with their surgeon, medical oncologist, and radiation oncologist about the benefits and risks of radiation and make a personal decision about whether or not to undergo radiation therapy. Well, that's it for this quick summary of this important research from the 2020 virtual San Antonio Breast Cancer Symposium. Overall, we continue on a fast track in breast cancer with many new and exciting therapies being actively studied and research helping support our patients do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you. ASCO: Thank you, Dr. Henry. You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

A number of groundbreaking and practice-changing studies were presented at the San Antonio Breast Cancer Symposium 2020. The RxPONDER, ADAPT, and PRIME-2 trials revealed patients who can forgo chemotherapy or radiotherapy, monarchE and PENELOPE-B showed conflicting results with CDK4/6 inhibitors, one study indicated that a new tool can guide adjuvant chemotherapy, and another study suggested that circulating tumor cells (CTCs) can predict overall survival (OS). Alan P. Lyss, MD, subprincipal investigator for Heartland Cancer Research NCORP, joined host David H. Henry, MD, to discuss these and other studies — their top 10 presentations from SABCS 2020 — in this episode. 1. Abstract GS3-07. Identifying patients whose symptoms are under-recognized during breast radiotherapy: Comparison of patient and physician reports of toxicity in a multicenter cohort. https://bit.ly/2MGCVEH This presentation could be one of the most important stories to emerge from SABCS 2020, according to Dr. Lyss. The trial included 9,868 breast cancer patients who received radiotherapy over an 8-year period. Investigators compared patient and physician reports of toxicity during radiotherapy, assessing four symptoms: pain, pruritus, edema, and fatigue. Physicians under-recognized moderate to severe pain 30.9% of the time, pruritus 36.7% of the time, edema 51.4% of the time, and fatigue 18.8% of the time. “The bottom line is: We’ve got to do better at this, and the first step in correcting it is to acknowledge that there is a problem. This abstract established that,” Dr. Lyss said.   2. Abstract GS2-03. Prime 2 randomised trial (postoperative radiotherapy in minimum-risk elderly): Wide local excision and adjuvant hormonal therapy +/- whole breast irradiation in women =/> 65 years with early invasive breast cancer: 10-year results. https://bit.ly/3omINAL The trial enrolled 1,326 women with histologically confirmed, unilateral invasive, hormone receptor-positive (HR+) breast cancer who were all 65 or older, had a tumor measuring 3 cm or less, had no nodal involvement, and were about to undergo breast-conserving surgery. The women were randomized 1:1 to receive adjuvant whole-breast irradiation or no radiotherapy in addition to adjuvant endocrine therapy. At 10 years, the rate of ipsilateral recurrence was significantly lower with radiotherapy than without it (0.9% vs 9.8%, P = .00008). The 10-year rate of regional recurrence was significantly lower with radiotherapy as well (0.5% vs. 2.3%, P = .014). There was no significant difference in the radiotherapy and no-radiotherapy arms when it came to distant recurrence (3.6% vs. 1.9%, P = .07), contralateral recurrence (2.2% vs. 1.2%, P = .20), non–breast cancer (8.7% vs. 10.2%, P = .41), metastasis-free survival (96.4% vs. 98.1%, P = .28), or OS (81.0% vs. 80.4%, P = .68). These results suggest radiotherapy could be omitted in this patient population, but the decision should be discussed and tailored to the individual patient, according to Dr. Henry.   3. Abstract GS1-01. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high-risk early breast cancer. https://bit.ly/38oSHwt The monarchE trial enrolled 5,637 women with HR+, HER2- early breast cancer. Cohort 1 included patients with four or more positive nodes, up to three positive nodes and a tumor size ≥ 5 cm, or grade 3 disease. Cohort 2 included women with up to three positive nodes and a Ki-67 index ≥ 20%. Patients in both cohorts were randomized to standard endocrine therapy alone or standard endocrine therapy with abemaciclib. The 2-year rate of invasive disease-free survival (IDFS) was 92.3% in the abemaciclib arm and 89.3% in the control arm (P = .0009). The 2-year distant relapse-free survival rate was 93.8% and 90.8%, respectively (P = .0009). Dr. Lyss said this is the first real advance in HR+ breast cancer adjuvant treatment in many years and has the potential to save thousands of lives. However, these are early data and should be interpreted with caution.   4. Abstract GS1-02. Phase III study of palbociclib combined with endocrine therapy (ET) in patients with hormone-receptor-positive (HR+), HER2-negative primary breast cancer and with high relapse risk after neoadjuvant chemotherapy (NACT): First results from PENELOPE-B. https://bit.ly/2XeQvRs The PENELOPE-B trial enrolled 1,250 women who had completed neoadjuvant chemotherapy and locoregional therapy. They were randomized to palbociclib plus endocrine therapy or endocrine therapy plus placebo. There was no significant difference in IDFS with palbociclib or placebo at 2 years (88.3% vs. 84%), 3 years (81.2% vs. 77.7%), or 4 years (73% vs. 72.4%).   5. Abstract GS4-10. Development and validation of a tool integrating the 21-gene recurrence score and clinicopathologic features to individualize prognosis for distant recurrence and prediction of absolute chemotherapy benefit in early breast cancer. https://bit.ly/38htoMD The RSClin tool integrates the 21-gene recurrence score and clinicopathologic features, including the grade of the tumor, the tumor size, and the patient's age. Researchers found that RSClin could guide adjuvant chemotherapy in HR+, HER2-, axillary node-negative breast cancer with greater precision, when compared with  clinicopathologic features or genomic data alone. RSClin is available at https://online.genomichealth.com/.   6. Abstract GS4-08. Clinical utility of repeated circulating tumor cell (CTC) enumeration as early treatment monitoring tool in metastatic breast cancer (MBC) - a global pooled analysis with individual patient data. https://bit.ly/2MGUrZp This study included 4,079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements in previous trials. The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether those levels were associated with OS. The median OS was 47 months for patients who were CTC-negative at both baseline and follow-up, 32.2 months for patients who were positive at baseline and negative at follow-up, 29.6 months for patients who were negative at baseline and positive at follow-up, and 17.8 months for patients who were positive at both time points. With the negative-negative group as the reference, hazard ratios were 1.52 for the positive-negative group, 1.74 for the negative-positive group, and 3.15 for the positive-positive group (P < .0001 for all).   7. Abstract GS3-00. First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25: SWOG S1007 (RxPonder). https://bit.ly/35bK7Px RxPONDER included 5,083 adults with HR+, HER2- breast cancer, one to three positive nodes, no contraindications to taxane and/or anthracycline-based chemotherapy, and recurrence scores of 25 or below. Patients were randomized 1:1 to receive endocrine therapy or chemo-endocrine therapy using three stratification factors: recurrence score (0-13 vs.14-25), menopausal status, and axillary nodal dissection vs. sentinel node biopsy. At a median follow-up of 5.1 years, there was no association between chemotherapy benefit and recurrence score values in the whole study population. In postmenopausal patients, there was no difference in 5-year IDFS between patients who received chemotherapy and those who didn’t (91.6% vs. 91.9%, P = .82). However, in premenopausal patients, the 5-year IDFS rate was 94.2% with chemotherapy and 89% without it (P = .0004). The data also showed an OS benefit with chemotherapy in premenopausal patients (P = .032), although this result is considered early due to few deaths at the time of evaluation. “These data really establish that postmenopausal women with between one to three involved nodes and an Oncotype DX score of 25 or less do not need post-operative adjuvant chemotherapy; end of discussion,” Dr. Lyss said. “For physicians who have been giving those women chemotherapy, these data are immediately practice- changing.”   8. Abstract GS4-04. Endocrine therapy alone in patients with intermediate or high-risk luminal early breast cancer (0-3 lymph nodes), Recurrence Score 10% or the patient had clinical N2 or N3 lymph nodes, the patient was assigned to receive neoadjuvant chemotherapy. The 5-year IDFS rate was 92.6% in patients with a recurrence score of 12-25 and a Ki-67 response and 93.9% in patients with a recurrence score of 0-11. The 5-year distant relapse-free survival was 95.6% and 96.3%, respectively. The 5-year OS was 97.3% and 98%, respectively. These results suggest Oncotype DX testing could spare the majority of HR+, HER2- patients with zero to three positive lymph nodes from receiving chemotherapy, Dr. Lyss said.   9. Abstract GS3-01. Additional efficacy endpoints from the phase 3 KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer. https://bit.ly/394UCVX In KEYNOTE-355, 847 patients with locally recurrent, inoperable or metastatic triple-negative breast cancer were randomized to receive pembrolizumab plus chemotherapy or chemotherapy plus placebo. Chemotherapy consisted of nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin. The median progression-free survival (PFS) was longer in the pembrolizumab arm, at 7.5 months, versus 5.6 months with chemotherapy alone (hazard ratio, 0.82). The PFS was superior with pembrolizumab regardless of the chemotherapy partner. However, higher PD-L1 expression was associated with a longer PFS, a higher overall response rate, and a longer duration of response.   10. Abstract GS3-06. Biomarker evaluation in the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. https://bit.ly/3hQ14nJ Trophoblast cell-surface antigen-2 (Trop-2) is highly expressed in triple-negative breast cancer. Sacituzumab govitecan (SG) consists of an anti-Trop-2 antibody coupled to SN-38, an active metabolite of irinotecan. In the ASCENT trial, patients with metastatic triple-negative breast cancer were randomized to SG or standard single-agent chemotherapy. A subgroup analysis of this trial showed that Trop-2 levels correlated with PFS and OS. Patients were divided into three groups by Trop-2 levels — low (H-score

A complete explanation of the scoring system for the oncotype DX test and it's benefits for early stage, node negative, hormone positive, Her2 negative breast cancer.  The trend towards "individualized oncology" in the past ten years has changed the focus from "one size fits all"  to examining the genomic characteristics of the tumor cells.  Early stage breast cancers treated prior to this diagnostic test were all given chemotherapy.  This test identifies tumors who would not respond to chemotherapy and allows these patients to skip this debilitating treatment and treat their cancer with hormone therapy.Support the show (https://give.ccf.org/team/320020)

Oncotype DX in N+ breast cancer, ADT timing, R may need less CHOP, Arimidex cancer prevention, Medical Scribes = good

Jame Abraham, MD, of the Cleveland Clinic joins Blood & Cancer host David H. Henry, MD, of Pennsylvania Hospital, Philadelphia to review two cases of breast cancer, focusing on when to use the 21-gene Oncotype DX breast recurrence score and how to apply the results.   Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, explores what happens when the patient minimizes their symptoms in order to keep getting treatment. *  *  *  Help us make this podcast better! Please take our short listener survey: https://www.surveymonkey.com/r/podcastsurveyOct2019 *  *  *  This Week in Oncology Not all lung cancer patients receive treatment By Richard Franki In the United States, just over 15% of patients with lung cancer receive no treatment, according to the American Lung Association. *  *  *  Breast cancer cases Case 1: A 46-year-old, premenopausal woman who has had a right breast lumpectomy with a 7-mm tumor that is invasive ductal, ER/PR positive, and HER2 negative. Since her tumor is small and low grade, would you do Oncotype DX recurrence score testing? Dr. Abraham recommends: Explain to the patient that her benefit from chemotherapy will be limited, but that she meets the tumor size requirement for the Oncotype DX assay and offer her the test. Case 2: A 57-year-old women who is postmenopausal with a grade 1 tumor that is 10mm, ER/PR positive, HER2 negative, with 4 of 17 positive lymph nodes. Is there an advantage to adding the Oncotype DX testing for this patient? Dr. Abraham recommends: Offer the patient chemotherapy; recommend against Oncotype DX testing. Show notes by Mary Ellen Schneider   References Sparano JA et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018 Jul 12;379(2):111-21. Sparano JA et al. Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer. N Engl J Med. 2019 Jun 20;380(25):2395-2405. *  *  *  For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd Ilana Yurkiewicz on Twitter: @ilanayurkiewicz

An interview with Dr. Lynn Henry from University of Utah Huntsman Cancer Institute on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." This guideline update includes data from the MINDACT and TAILORx trials to clarify the recommendations for patients with hormone receptor-positive, HER2 not overexpressed, axillary node-negative early breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines  TRANSCRIPT 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin. And today, I'm interviewing Dr. Lynn Henry from the University of Utah Huntsman Cancer Institute, lead author on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you for being here today, Dr. Henry. Thank you very much for the invitation. So this guideline was updated to incorporate new data from the TAILORx and the MINDACT trials. So can you give us an overview of these trials and their results? Sure. So patients with hormone receptor-positive, HER2 negative breast cancer, are generally treated with anti-estrogen treatment and are sometimes also recommended to have chemotherapy. Since these tumors don't always respond well to chemotherapy, tests have been developed that provide more information about how much benefit, in terms of reduction of the likelihood of cancer coming back, an individual patient is likely to get from treatment with chemotherapy. It is important that the benefit of a treatment outweighs the risk of toxicity from the treatment. Two of those tests are called Oncotype DX and MammaPrint. And they have recently been tested in large clinical trials. So TAILORx is a large prospective trial that tested the Oncotype DX assay. In the Oncotype DX assay, a tumor is tested to get more information about how likely a cancer is to return and how much benefit the patient is likely to get from chemotherapy. Scores on this assay can range from 0 to 100. Previously, a study showed that patients whose tumors had scores of 10 or less, and who received five years of anti-estrogen treatment, were very unlikely to have their tumors return. So chemotherapy is not recommended for them. For patients with higher scores, above 30, we also already knew that chemotherapy is likely to decrease the chance of cancers in those patients, and, so, therefore, we generally recommend chemotherapy for women with higher scores. In the TAILORx trial, the recently reported trial, more than 6,700 women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer had their tumors tested and were found to have Oncotype DX recurrent scores between 11 and 25, which is in that intermediate range or at the higher end of the low range. Before this trial was conducted, many people with tumors like these, in the intermediate range, were treated with both chemotherapy and endocrine therapy because we weren't sure how much benefit they would obtain from chemotherapy, and we didn't want to leave out a potentially helpful treatment. In this trial, patients were randomized, or randomly assigned by a computer, to treatment with chemotherapy followed by endocrine therapy or to treatment with endocrine therapy alone. The trial was mainly looking at whether leaving out chemotherapy would increase the likelihood of invasive cancer returning. And, luckily, overall, the trial showed that the likelihood of cancer returning in those patients who got endocrine therapy alone, without chemotherapy, wasn't significantly different compared to those who were treated with chemotherapy followed by endocrine therapy. They also looked, specifically, at the group of women who were 50 years of age or younger. So mostly premenopausal women. Now, this was an exploratory question, meaning it provides information that may be correct, but it hasn't been as fully tested as the main question about what do we do for all women? In these younger women, there appeared to be some benefit from chemotherapy in those whose tumors had scores from 21 to 25, and, also possibly, in those whose tumors had scores from 16 to 20. Therefore, we still consider giving chemotherapy to younger women with Oncotype DX scores in the middle range, from 16 to 25, but not to women over age 50. So that was the TAILORx trial. The MINDACT trial was a bit different. It was testing the MammaPrint assay and the trial also included primarily women with hormone receptor-positive, HER2 negative breast cancer. But in this case, most women's sorry lymph nodes were negative, although a few women had up to three lymph nodes involved. In that trial, patient's risk of disease recurrence was assessed in two ways. First, it was assessed based on clinical factors. So the size of the tumor, how many lymph nodes were involved, and the estrogen receptor, progesterone receptor, and HER2 receptors. Second, it was assessed based on genomic factors-- that was using the MammaPrint test. So if patients were low for both clinical factors and genomic factors, they only were treated with anti-estrogen therapy. If they were high for both clinical factors and genomic factors, then they were treated with chemotherapy followed by anti-estrogen therapy. However, if they were high for one and low for the other, then they were randomized to either endocrine therapy alone or chemotherapy followed by endocrine therapy. So it was a little bit of a confusing trial. In the MINDACT trial, those patients who were thought to be high risk based on their clinical risk, so the size of the tumor, the number of lymph nodes, but then found to be low risk on the MammaPrint assay. They found that there was no benefit to treatment with chemotherapy in terms of how likely a woman was to develop distant metastatic disease. And if they were low risk, based on the clinical assessment, then there didn't appear to be a benefit of actually doing the test, the assay, because chemotherapy wouldn't be recommended for the patient, regardless of the results. So that was the MINDACT trial. So what are the new and updated recommendations for the guideline? Yes, so in this guideline, we, based on the TAILORx trial, we made new recommendations for use of the Oncotype DX results. All of these results apply to women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer. So for women older than age 50, if they have an Oncotype score of 25 or lower, then clinicians may offer endocrine therapy and no chemotherapy. However, for women age 50 or under, if they have an Oncotype score of 15 or lower, 15, then, clinicians may offer endocrine therapy and no chemotherapy. But if the score is 16 to 25, then chemotherapy can be considered in addition to endocrine therapy. So it made a difference in that gray area in the middle. For all women with score 26 to 30, chemotherapy may be considered. And for scores above 30, chemotherapy should definitely be considered. The data from the MammaPrint trial actually aren't that new. Results from that trial were originally published in 2016. However, that was after the original guideline was published, so we wanted to add these results to these updated guidelines for completeness. For a patient with hormone receptor-positive, HER2 negative, node-negative breast cancer, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then treatment with chemotherapy can be avoided. If a patient is thought to be at low clinical risk, the MammaPrint should not be used as chemotherapy can be avoided regardless. And for a patient with hormone receptor-positive, HER2 negative breast cancer, but who has one to three positive lymph nodes, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then it is possible that chemotherapy could be avoided, especially if only one lymph node is involved. So I think the bottom line for this part is that both of these tests-- there are now women who previously would have been recommended to have chemotherapy that maybe now we can avoid chemotherapy based on using these assays on their tumors. So why are these changes so important and how will they affect practice? Yes, that's a good question. Before the publication of the TAILORx trial, we had good information about how to treat patients who had either very low or very high Oncotype scores. But we really weren't sure how best to treat those patients who scores fell in the middle. Now, we have important information to guide decisions about chemotherapy for patients with intermediate scores. For many patients with scores in this range, these new results mean they will be able to avoid chemotherapy and just get endocrine therapy. While these results don't give us answers for every patient, they do provide more information that oncologists can use when having discussions with patients about the benefits and risks of chemotherapy. And what does this mean for patients with early-stage invasive breast cancer? And what should they talk to their doctors about? So as a result of both of these trials, we now have additional tools that can help oncologists provide more individualized treatment recommendations for patients and really assess whether or not chemotherapy, in addition to endocrine therapy, is likely to provide benefits. Knowing which patients' tumors will respond to chemotherapy can help some patients avoid unwanted side effects from a treatment that's not likely to actually give them much benefit. Now, these tests aren't appropriate for everyone and don't provide all the answers, but they are an important step in the right direction for providing more personalized treatment for women newly-diagnosed with certain types of breast cancer. Patients should talk with their doctors about whether these tests are right for them when they're making important decisions about whether or not they should receive treatment with chemotherapy. Great. Thank you, Dr. Henry, for this informative overview of the guideline. Keeping these clinical practice guidelines updated is really crucial and it takes a lot of careful thought to ensure these recommendations represent the evidence. So thank you for coming on the podcast to discuss the "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you very much for the opportunity to talk with you today. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

Host Cyrus Webb welcomes Dr. Deepa Halaharvi and Jennfier Merschdorf to #ConversationsLIVE to discuss their own breast cancer survival stories, the Oncotype DX test and the importance of discovering the right breast cancer treatment.  Find out more information at www.nomattermyage.org.   

  William J. Gradishar, MD, of Feinberg School of Medicine and Northwestern Medicine in Chicago, chats with David H. Henry, MD, host of Blood & Cancer, to review some of the top breast cancer research presented at the 2019 annual meeting of the American Society of Clinical Oncology. Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about dealing with help-seeking and help-rejecting patients.   Show notes This episode discusses three randomized, controlled phase 3 trials that were presented at ASCO 2019:  KRISTINE trial (abstract 500) Design: Patients with HER2-positive breast cancer were randomized to receive either neoadjuvant trastuzumab, pertuzumab, and chemotherapy (docetaxel, carboplatin) vs. trastuzumab emtansine plus pertuzumab. Primary endpoint: Pathological complete response rate. Secondary endpoints: Toxicity, event-free survival, invasive disease-free survival. Conclusion: Docetaxel, carboplatin, and trastuzumab plus pertuzumab resulted in a higher rate of pathological complete response than did trastuzumab emtansine plus pertuzumab, but was associated with more serious adverse events. PREDIX trial (abstract 501) Design: Patients with HER2 positive and hormone receptor positive breast cancer were randomized to receive either neoadjuvant trastuzumab emtansine monotherapy vs. docetaxel, trastuzumab, and pertuzumab. Primary endpoint: Pathological complete response rate. Secondary endpoints: Toxicity and quality of life. Conclusions: Trastuzumab emtansine monotherapy was better tolerated while maintaining comparable PCR rate as the group which received docetaxel, trastuzumab, and pertuzumab.  TAILORx trial (abstract 503) Design: Patients with node-negative, estrogen receptor–positive breast cancer with an Oncotype DX recurrence score of 11-25 were randomized to receive either hormone therapy alone or hormone therapy together with combination chemotherapy. Primary endpoint: Rate of distant recurrence at 9 years.  Conclusions: There was no benefit from chemotherapy for younger women (aged 50 years or younger) with a recurrence score of 16-20 and at low risk clinically (small tumor size and favorable histologic grade). Those age younger than age 50 years with a score of 16-20, but high risk clinically, may benefit from chemotherapy. Much of the benefit derived from chemotherapy was because of ovarian suppression. Using the recurrence score in combination with clinical risk stratification allows clinicians to identify more young women who can be spared chemotherapy, and more young women who may benefit from antiestrogen therapy.   Show notes by Sugandha Landy, MD, a resident in the department of internal medicine, University of Pennsylvania, Philadelphia.   References J Clin Oncol 37. 2019 May 20 (suppl; abstr 500). doi: 10.1200/JCO.2019.37.15_suppl.500. J Clin Oncol 37. 2019 May 20 (suppl; abstr 501). doi: 10.1200/JCO.2019.37.15_suppl.501. J Clin Oncol 37. 2019 May 20 (suppl; abstr 503). doi: 10.1200/JCO.2019.37.15_suppl.503. Lancet Oncol. 2018 Jan;19(1):115-26. N Engl J Med. 2019 Jun 20;380:2395-405.    For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd Ilana Yurkiewicz on Twitter: @ilanayurkiewicz  

Mr. Anson Tharayanil, a Medical Science Liaison from Genomic Health rejoins Joel Nowak from Cancer ABCs to talk about another test for men diagnosed with low or favorable medium risk prostate cancer, the Oncotype DX Genomic Prostate Score.The test should be used along side the traditional measures we use like biopsy Gleason Grade and scans to help a man decide if he is a good candidate for Active Surveillance (AS) as opposed to having surgical or a radiation intervention. Biopsies only sample 1% of a man's prostate gland, so as a stand alone measure it does not provide us with an accurate understanding of the aggressiveness of a man's prostate cancer. When added to the other measures, we traditionally still fall far short of accurately knowing which prostate cancers need immediate treatment and which can be monitored. Research shows that at least 20% of men who qualify for AS using the traditional measures if they go on and have surgery they find that their cancer is actually a lion in sheep's clothing, or is very dangerous. The Oncotype DX Genomic Prostate Score has been well validated and should automatically be used by any man who is trying to decide if they are a good candidate for Active Surveillance. Support the show (https://www.cancerabcs.org/new-page-2/)

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. The 2019 ASCO Annual Meeting, held May 31 to June 4, brought together physicians, researchers, patient advocates, and other health care professionals from around the world to present and discuss the latest research in cancer treatment and patient care. In the annual Research Round Up podcast series, Cancer.Net Associate Editors share their thoughts on the most exciting scientific research to come out of this year’s ASCO Annual Meeting and what it means for patients. First, Dr. Lynn Henry will discuss 3 studies that explored new treatment options for women with breast cancer, including a study on immunotherapy for triple-negative breast cancer and 2 studies on treatment for hormone receptor positive, HER2-negative breast cancer. She also discusses research on the effects of a low-fat diet in women diagnosed with breast cancer, and a study on whether pregnancy after breast cancer increased the risk of recurrence.   Dr. Henry is an Associate Professor and Interim Division Chief of Oncology in the Department of Medicine at the University of Utah and Director of Breast Medical Oncology at the Huntsman Cancer Institute. She is also the Cancer.Net Associate Editor for Breast Cancer. Dr. Henry: Hi. My name is Dr. Lynn Henry. I'm a medical oncologist who specializes in treating breast cancer at the University of Utah. Today, I'm going to discuss research on breast cancer that was presented at the 2019 ASCO Annual Meeting in Chicago. In particular, I'm going to focus on the results of some clinical trials that directly impact how oncologists treat patients with breast cancer. First, I'm going to give just a very brief overview of the types of breast cancer and then talk about some research that was presented on triple-negative and hormone-receptor-positive breast cancer. Then I'm going to briefly review findings related to diet and breast cancer as well as pregnancy after breast cancer in women with BRCA mutations. As a quick reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone-receptor positive or estrogen-receptor positive, and those are stimulated to grow by estrogen. We treat those cancers with anti-estrogen treatments or anti-hormone treatments to block estrogen or lower the estrogen level in the body. Other breast cancers are called HER2-positive. These are often more aggressive cancers. But because they have extra copies of HER2, they often respond to treatments that block HER2. And finally, there are breast cancers that don't have hormone receptors or HER2, and these are called triple-negative breast cancer. So first, I'm going to focus on this type, triple-negative breast cancer. Until recently, most of the time, we treated triple-negative breast cancer with chemotherapy because we hadn't found other drugs that worked very well. There's a new type of drug, however, called immunotherapy that tries to use a patient's immune system to help fight the breast cancer. Early in 2019, the FDA approved a new treatment for triple-negative breast cancer that is a combination of a chemotherapy called Abraxane and a new immune drug called atezolizumab or Tecentriq. The combination increased the length of time until cancer progressed or grew. Overall, the treatment was fairly well tolerated. But we did learn that in order for the treatment to work, the cells surrounding the cancer have to have at least a small amount of a very specific protein called PD-L1. So at this recent ASCO meeting, we heard an update about this treatment. In the trial, the patients whose cancers had the PD-L1 protein and who got the combination treatment lived 7 months longer than those who got just the chemotherapy, which was an increase from 18 months to just over 2 years. This is an important first step towards finding a better treatment for this difficult type of triple-negative breast cancer. And this treatment is currently available to patients. Additional clinical trials are going on now to try to find even better combinations of chemotherapy and immune therapies to treat this type of cancer. So next, I'm going to talk about hormone-receptor-positive breast cancer. There were two trials of this type of cancer that had important results presented at the ASCO meeting. First, I'll focus on the treatment of early-stage node-negative breast cancer that is hormone-receptor positive and HER2 negative. The Oncotype DX test is a test we commonly run on tumors of this type to help determine whether treatment with chemotherapy is likely to be helpful. For this test, if your tumor has a score over 25, then chemotherapy is generally recommended in addition to anti-hormone therapy. If you have a score under 11, then chemotherapy is not recommended and a patient should receive only anti-hormone therapy. But for those with scores between 11 and 25, it was unclear how beneficial it was to receive chemotherapy. Last year, the results of the TAILORx trial were reported. And that showed that for women over the age of 50, if their tumor had a score between 11 and 25, they were not likely to get benefit from chemotherapy. However, it turned out it was a bit more complicated for women aged 50 and under. For those with scores between 11 and 15, chemotherapy was not likely to be beneficial. However, for those who score 16 to 25, chemotherapy might be beneficial. So we got some answers but not everything. At this recent ASCO meeting, additional information was reported to help guide treatment decision making for this middle group of women aged 50 and under. So for women whose scores were at the higher end, 21 to 25, chemotherapy was found to be likely to be beneficial. However, in that middle group, the 16 to 20 group, chemotherapy might be beneficial but generally only for women with higher risk cancers, meaning larger cancers or higher grade. This information is helpful because it provides more information for oncologists and for patients when they are discussing whether or not chemotherapy should be included as part of their treatment. So switching gears a little, still staying with premenopausal women and hormone-receptor-positive HER2-negative cancer, but now thinking about metastatic breast cancer, so cancer that has spread. We now have additional information about treatment with an anti-hormone therapy plus an additional drug called the CDK4/6 inhibitor. We've routinely been recommending this treatment combination because it leads to a longer time before the cancer progresses. But until now, we didn't know if it actually allows women with this type of cancer to live longer. The results of the MONALEESA-7 trial, which looked at the combination of an anti-hormone therapy plus the drug called ribociclib, showed that women who received the combination instead of anti-hormone therapy alone live almost 30% longer. So looking at women 3 and a half years after they started treatment, just over 70% of the women who were treated with ribociclib plus anti-hormone therapy were alive compared to just under half of women treated with anti-hormone therapy alone. So these results reinforce that this is an excellent first approach to treatment of premenopausal women who have newly diagnosed, hormone-receptor-positive HER2-negative metastatic breast cancer. So in addition to studies looking at these specific types of breast cancer, there were 2 other interesting studies that were applicable to breast cancer more generally. So there was a large study that was reported that looked at whether having a low-fat diet reduced the likelihood of developing triple-negative breast cancer. So in this study, postmenopausal without cancer were randomized to either a low-fat diet or their usual diet and followed for many, many years. Over time, some of these women developed breast cancer with no difference between those who followed the low-fat diet or the regular diet. However, in this new report, they looked specifically at the women who developed breast cancer who were enrolled in this trial. Fewer women died from their breast cancer if they ate the low-fat diet, especially if they had preexisting high cholesterol, diabetes, and obesity. These findings suggest that having a low-fat diet may actually reduce the risk of dying overall and also specifically from breast cancer. Now, these need to be validated, and we don't quite understand why this would be the case. But in general, it seems like having a low-fat diet, avoiding high cholesterol, diabetes, and obesity is a good thing. And then finally, 1 question that comes up often is whether it is safe to have a baby after the diagnosis of breast cancer. This is especially concerning for patients who have a mutation in genes called BRCA1 or BRCA2 since those mutations greatly increase their risk of developing both breast and ovarian cancer and also leads to the diagnosis of breast cancer at an early age. In addition, patients with these mutations are often recommended to have their ovaries removed at a young age. So in this study, patients who became pregnant did so about 4 and a half years after they were diagnosed with breast cancer. There was no apparent increase in miscarriage, preterm birth, or birth defects compared to what would be expected in women without cancer. And in the patients, there was no increase in the risk of breast cancer recurrence compared to those who did not become pregnant. And in fact, those who became pregnant were slightly less likely to have their cancer return, especially those who had mutations in BRCA1. So while there are some limitations to the study, the findings are reassuring that there does not appear to be an increase in risk of breast cancer returning in these patients with BRCA mutations who become pregnant after breast cancer diagnosis. So overall, as you can see, there's a lot of exciting research going on across all the different subsets of breast cancer. The results of many important clinical trials were reported at the recent ASCO meeting, and there are many more trials ongoing that will hopefully result in the approval of multiple new effective treatments for breast cancer. In addition, there's research going on examining the impact of treatment on patients with breast cancer and trying to improve the lives of those living with breast cancer. Clinical trials are critical for the development of these new treatments. Well, that's it for this quick summary of this important research from ASCO 2019. Overall, we continue on a fast track in breast cancer, with many new and exciting therapies being actively studied and research helping support our patients do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you very much. ASCO: Thank you, Dr. Henry. Next, Dr. Ezra Cohen will discuss several studies that looked at using immunotherapy and targeted therapy to treat different types of head and neck cancer. Dr. Cohen is Associate Director of Translational Science and leads the Solid Tumor Therapeutics research program at Moores Cancer Center at UC San Diego Health. He is the Cancer.Net Associate Editor for Head and Neck Cancer. Dr. Cohen: Hi. I'm Dr. Ezra Cohen from UC San Diego Moores Cancer Center. Today, I'm going to talk about research on head and neck cancer that was presented at the 2019 ASCO Annual Meeting. I think the most impactful presentation at the meeting was a follow-up on the KEYNOTE-048 study, which implemented the drug pembrolizumab, an anti-PD-1 antibody in first-line recurrent metastatic head and neck cancer. These were patients who were treated with curative intent or presented with metastatic disease, and either way, either had recurrence or eventually developed metastases. The first-line standard of care for these patients used to be the so-called extreme regimen, which involved platinum, 5-FU, and cetuximab. This was validated in an earlier phase III study that was conducted about 10 years ago and was the approved first-line regimen for these patients. In KEYNOTE-048, this extreme regimen was tested against either pembrolizumab alone or pembrolizumab, platinum, and 5-FU, in other words, substituting cetuximab for pembrolizumab in one of the experimental arms. We'd initially seen the interim analysis data at last year's ESMO meeting, but this year, we have the final analysis presented at ASCO. And what we saw was that both experimental arms actually achieved an improvement in overall survival compared to the extreme regimen. Interestingly, for pembrolizumab alone, this occurred in patients whose tumors expressed some level of PD-L1. That was evaluated by something called the composite score and takes into account both stromal and tumor cell staining of PD-L1. In fact, even at a very low level—that is CPS greater than or equal to 1—pembrolizumab monotherapy was superior to the extreme regimen with respect to overall survival. For all patients, the regimen of pembrolizumab plus chemotherapy was superior to the extreme regimen irrespective of PD-L1 staining. What we saw at this year's ASCO meeting was that, in fact, first, the higher the expression of PD-L1, the greater the benefit one derived from pembrolizumab either as monotherapy or in combination with chemotherapy. And in patients who had higher levels of PD-L1 and received both pembrolizumab and chemotherapy, the overall survival was quite remarkable with a hazard ratio of just higher than 0.6. In fact, we now have FDA approval in the United States for pembrolizumab monotherapy with tumors that have some expression level of PD-L1—that is CPS greater than or equal to one—or for all comers in patients who either the CPS status is unknown or patients whose tumors don't express PD-L1. Beyond KEYNOTE-048, we saw interesting data in first-line recurrent metastatic using a regimen of taxane, platinum, and 5-FU compared to the same extreme regimen that we just mentioned. That regimen turned out to be much better tolerated with fewer adverse events but with no improvement in overall survival, giving us a regimen that we could substitute for the extreme regimen if one wanted to, realizing that it does not involve immunotherapy, and for some patients, this may still be an appropriate treatment. Beyond the first-line recurrent metastatic studies, we saw a few interesting trials looking at targeted therapy in head and neck cancer but specific subsets. The first was in patients whose tumors expressed HER2 at very high levels—that is HER2 amplified—and had salivary ductal carcinoma. We've known that a proportion of salivary ductal carcinoma patients' tumors amplify this gene, HER2, similar to breast cancer and some other malignancies and that trastuzumab may, in fact, be effective. Well, in this study conducted by the Memorial Sloan Kettering Group, an antibody-drug conjugate trastuzumab emtansine was employed as a single agent in these patients whose, again, tumors amplified HER2. And what they saw was a remarkable 90% response rate. Now, this was only in 10 patients, so the study is small, but I think it's safe to say that this drug appears to be quite effective in patients with HER2-amplified salivary ductal carcinoma. Along those lines, in the subset of thyroid cancer patients whose tumors either mutate or have a RET fusion, the gene RET, there appeared to be very high efficacy for a novel agent that targets the RET oncogene. This was in both patients with medullary thyroid cancers that often have a RET mutation or in papillary thyroid cancers whose tumors often have a fusion of the same RET gene. Again, underscoring the idea that if we can target a driver even in a relatively small subset of patients, the benefit may be quite large. Along those lines, we had seen prior data for track inhibitors in patients who have in track fusions. And again, this applies to subsets of head and neck cancer patients that have either salivary gland cancers or thyroid cancers. Lastly, we continue to see emerging promising data of combinations with immunotherapy, and 2 highlights from ASCO were pembrolizumab with cetuximab showing a response rate of over 40% in a small group of patients and pembrolizumab with a TLR9 agonist called SD-101 showing about a 30% response rate. Of course, these data are very early and uncontrolled, and so we have to follow these stories further along to see if, indeed, these early signs of efficacy turn out to validate. But the idea that further combinations of immunotherapies eventually making their way to larger studies and hopefully approval is now well enforced in head and neck cancer. Thank you very much for your attention and hope you enjoyed the ASCO 2019 Annual Meeting. ASCO: Thank you Dr. Cohen. Next, Dr. Charles Loprinzi will discuss new research on ways to prevent or treat nausea and vomiting caused by cancer treatment. Dr. Loprinzi is a medical oncologist and the Regis Professor of Breast Cancer Research at the Mayo Clinic. He is also the Cancer.Net Associate Editor for Psychosocial Oncology. Dr. Loprinzi: Hello, I'm Charles Loprinzi, Regis Professor of Breast Cancer Research at Mayo Clinic. I'm going to be talking today about chemotherapy-induced nausea and vomiting. Now, chemotherapy can cause a lot of nausea and vomiting. That's well known, for years and years, by many people. It's not all types of chemotherapy, but some chemotherapy drugs cause a lot of nausea and vomiting, and others cause little to none. It's not as big a problem now as it was decades ago when we didn't have good drugs to try to prevent nausea and vomiting. Many drugs over the time have been developed for trying to prevent this nausea and vomiting problem. Examples of the drugs that cause a lot of nausea and vomiting are Cisplatinum, and Adriamycin and cyclophosphamide is a combination that is oftentimes used for patients with breast cancer. So in the past, we have developed many, many drugs for this. Three of the drugs that have commonly been used for the last many, many years for treatment or prevention of nausea and vomiting associated with chemotherapy are corticosteroid medications like Dexamethasone. It's quite cheap. It's got some side effects, but relatively cheap. Then there's a group called 5-HT3 receptor antagonists. I didn't make up that name, but that's the long name for it. They're relatively expensive, some more expensive than other ones. And then there's another group called NK1 receptor antagonists, and they can be quite expensive, sometimes being hundreds of dollars for each dose that's given to try to prevent nausea and vomiting related to chemotherapy. So a couple years ago, 2016, there was a report in the New England Journal of Medicine, which is a prominent journal for us in the business, that looked at a drug called olanzapine. It's a relatively cheap drug. It's a drug that was developed for psychosis-type problems, given for long term in those patients. But it had been noted that if it's given for just a few days, it seems to markedly improve or decrease the instance of nausea and vomiting, or if people were having nausea and vomiting, it appears actually to help and reverse that particular problem. So this trial looked at 10 milligrams of this drug for 4 days, given before chemotherapy, and then for 3 more days after that. Patients who were on this study got the 3 drugs that I talked about before with the olanzapine or with the placebo. And it noted that it improved things by quite a bit. The patients who had what we call a complete response, which means no vomiting and no need to take extra medications because of nausea and vomiting, improved from 41% of the patients who were on the placebo, to 64% who were on the olanzapine, a 23% improvement. And if we looked at a different endpoint there, the number of patients who had no nausea during the five days after chemotherapy, it was 22% in the group that got the placebo and improved to 37% in the group that didn't. So it was a good result in that area. One of the problems with this drug is that it can cause some sedation, cause some drowsiness for some patients. Most patients, not much, but some patients, it's a problem. So most trials that have been done in the past use this 10-milligram dose. And what we learned at ASCO in 2019, our main meeting that we have once a year, was that people looked at a 5-milligram dose and had looked at 5 milligrams instead of the 10 milligrams. And what it showed is that the results seemed to be quite similar to what was seen with 10 milligrams. They did the study quite the same as what had been reported in the previous trial and the results looks similar. They didn't compare 5 milligrams versus 10 milligrams, which would've been nice because then we would have better information along that line. They did note that there was drowsiness that some patients had, and it looks similar to what was seen with the 10-milligram dose. But these data support, but don't prove, that giving 5 milligrams does look like it's good in this particular setting. So data from this year also supported that instead of giving the drug during the day when getting the chemotherapy, sometimes, people take it at bedtime, and there, the drowsiness is not as big a problem because you want to be drowsy at bedtime. So it's not proven that it works as well at bedtime, but it suggests that that actually is the case. Data from this year also supported that if you looked at those 3 drugs I mentioned before and just took out that 1 really, really expensive one, the NK1 receptor antagonist, and put the olanzapine in there instead, that very cheap medication, that that looked like that one with the olanzapine did better than the very expensive one. Not a whole lot better; they looked similar, but a little bit better in that setting, and it was a whole lot cheaper. This was also seen in a publication that came out a couple of years ago which showed the same sort of result. Again, not proof that it's beneficial, that it's okay to do that, but it looked better. So the next obvious question that comes up then is when you have these 4 drugs that you give, the 3 drugs I mentioned before and this fourth one, what about if you take away that more expensive one and see how they do there? So there was a trial at the ASCO meeting that suggested that the addition of that expensive medications didn't provide a whole lot more benefit. Right now, there is a trial going on across the United States, with about 800 patients who are scheduled to go on this trial, and it's approving about 30 patients a month, which is a pretty good accrual rate, which is looking at this particular question where people would get the 4-drug regimen versus 3 drugs where they take away the expensive intravenous medication. So, in summary, 35 to 40 years ago, when I started my cancer career, when I was about 10 years old, most patients had a lot a trouble with nausea and vomiting with drugs like Cisplatinum. Now, this a minority of patients who have a lot of problems, and we're continuing to find new things that will make things better along this line. Thank you for your attention. ASCO: Thank you Dr. Loprinzi. Learn more about these topics and other research presented at the 2019 ASCO Annual Meeting at www.cancer.net. If this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. And stay tuned for additional Research Round Up podcasts coming later this summer. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

An interview with Dr. Lynn Henry from University of Utah Huntsman Cancer Institute on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." This guideline update includes data from the MINDACT and TAILORx trials to clarify the recommendations for patients with hormone receptor-positive, HER2 not overexpressed, axillary node-negative early breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines  TRANSCRIPT 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin. And today, I'm interviewing Dr. Lynn Henry from the University of Utah Huntsman Cancer Institute, lead author on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you for being here today, Dr. Henry. Thank you very much for the invitation. So this guideline was updated to incorporate new data from the TAILORx and the MINDACT trials. So can you give us an overview of these trials and their results? Sure. So patients with hormone receptor-positive, HER2 negative breast cancer, are generally treated with anti-estrogen treatment and are sometimes also recommended to have chemotherapy. Since these tumors don't always respond well to chemotherapy, tests have been developed that provide more information about how much benefit, in terms of reduction of the likelihood of cancer coming back, an individual patient is likely to get from treatment with chemotherapy. It is important that the benefit of a treatment outweighs the risk of toxicity from the treatment. Two of those tests are called Oncotype DX and MammaPrint. And they have recently been tested in large clinical trials. So TAILORx is a large prospective trial that tested the Oncotype DX assay. In the Oncotype DX assay, a tumor is tested to get more information about how likely a cancer is to return and how much benefit the patient is likely to get from chemotherapy. Scores on this assay can range from 0 to 100. Previously, a study showed that patients whose tumors had scores of 10 or less, and who received five years of anti-estrogen treatment, were very unlikely to have their tumors return. So chemotherapy is not recommended for them. For patients with higher scores, above 30, we also already knew that chemotherapy is likely to decrease the chance of cancers in those patients, and, so, therefore, we generally recommend chemotherapy for women with higher scores. In the TAILORx trial, the recently reported trial, more than 6,700 women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer had their tumors tested and were found to have Oncotype DX recurrent scores between 11 and 25, which is in that intermediate range or at the higher end of the low range. Before this trial was conducted, many people with tumors like these, in the intermediate range, were treated with both chemotherapy and endocrine therapy because we weren't sure how much benefit they would obtain from chemotherapy, and we didn't want to leave out a potentially helpful treatment. In this trial, patients were randomized, or randomly assigned by a computer, to treatment with chemotherapy followed by endocrine therapy or to treatment with endocrine therapy alone. The trial was mainly looking at whether leaving out chemotherapy would increase the likelihood of invasive cancer returning. And, luckily, overall, the trial showed that the likelihood of cancer returning in those patients who got endocrine therapy alone, without chemotherapy, wasn't significantly different compared to those who were treated with chemotherapy followed by endocrine therapy. They also looked, specifically, at the group of women who were 50 years of age or younger. So mostly premenopausal women. Now, this was an exploratory question, meaning it provides information that may be correct, but it hasn't been as fully tested as the main question about what do we do for all women? In these younger women, there appeared to be some benefit from chemotherapy in those whose tumors had scores from 21 to 25, and, also possibly, in those whose tumors had scores from 16 to 20. Therefore, we still consider giving chemotherapy to younger women with Oncotype DX scores in the middle range, from 16 to 25, but not to women over age 50. So that was the TAILORx trial. The MINDACT trial was a bit different. It was testing the MammaPrint assay and the trial also included primarily women with hormone receptor-positive, HER2 negative breast cancer. But in this case, most women's sorry lymph nodes were negative, although a few women had up to three lymph nodes involved. In that trial, patient's risk of disease recurrence was assessed in two ways. First, it was assessed based on clinical factors. So the size of the tumor, how many lymph nodes were involved, and the estrogen receptor, progesterone receptor, and HER2 receptors. Second, it was assessed based on genomic factors-- that was using the MammaPrint test. So if patients were low for both clinical factors and genomic factors, they only were treated with anti-estrogen therapy. If they were high for both clinical factors and genomic factors, then they were treated with chemotherapy followed by anti-estrogen therapy. However, if they were high for one and low for the other, then they were randomized to either endocrine therapy alone or chemotherapy followed by endocrine therapy. So it was a little bit of a confusing trial. In the MINDACT trial, those patients who were thought to be high risk based on their clinical risk, so the size of the tumor, the number of lymph nodes, but then found to be low risk on the MammaPrint assay. They found that there was no benefit to treatment with chemotherapy in terms of how likely a woman was to develop distant metastatic disease. And if they were low risk, based on the clinical assessment, then there didn't appear to be a benefit of actually doing the test, the assay, because chemotherapy wouldn't be recommended for the patient, regardless of the results. So that was the MINDACT trial. So what are the new and updated recommendations for the guideline? Yes, so in this guideline, we, based on the TAILORx trial, we made new recommendations for use of the Oncotype DX results. All of these results apply to women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer. So for women older than age 50, if they have an Oncotype score of 25 or lower, then clinicians may offer endocrine therapy and no chemotherapy. However, for women age 50 or under, if they have an Oncotype score of 15 or lower, 15, then, clinicians may offer endocrine therapy and no chemotherapy. But if the score is 16 to 25, then chemotherapy can be considered in addition to endocrine therapy. So it made a difference in that gray area in the middle. For all women with score 26 to 30, chemotherapy may be considered. And for scores above 30, chemotherapy should definitely be considered. The data from the MammaPrint trial actually aren't that new. Results from that trial were originally published in 2016. However, that was after the original guideline was published, so we wanted to add these results to these updated guidelines for completeness. For a patient with hormone receptor-positive, HER2 negative, node-negative breast cancer, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then treatment with chemotherapy can be avoided. If a patient is thought to be at low clinical risk, the MammaPrint should not be used as chemotherapy can be avoided regardless. And for a patient with hormone receptor-positive, HER2 negative breast cancer, but who has one to three positive lymph nodes, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then it is possible that chemotherapy could be avoided, especially if only one lymph node is involved. So I think the bottom line for this part is that both of these tests-- there are now women who previously would have been recommended to have chemotherapy that maybe now we can avoid chemotherapy based on using these assays on their tumors. So why are these changes so important and how will they affect practice? Yes, that's a good question. Before the publication of the TAILORx trial, we had good information about how to treat patients who had either very low or very high Oncotype scores. But we really weren't sure how best to treat those patients who scores fell in the middle. Now, we have important information to guide decisions about chemotherapy for patients with intermediate scores. For many patients with scores in this range, these new results mean they will be able to avoid chemotherapy and just get endocrine therapy. While these results don't give us answers for every patient, they do provide more information that oncologists can use when having discussions with patients about the benefits and risks of chemotherapy. And what does this mean for patients with early-stage invasive breast cancer? And what should they talk to their doctors about? So as a result of both of these trials, we now have additional tools that can help oncologists provide more individualized treatment recommendations for patients and really assess whether or not chemotherapy, in addition to endocrine therapy, is likely to provide benefits. Knowing which patients' tumors will respond to chemotherapy can help some patients avoid unwanted side effects from a treatment that's not likely to actually give them much benefit. Now, these tests aren't appropriate for everyone and don't provide all the answers, but they are an important step in the right direction for providing more personalized treatment for women newly-diagnosed with certain types of breast cancer. Patients should talk with their doctors about whether these tests are right for them when they're making important decisions about whether or not they should receive treatment with chemotherapy. Great. Thank you, Dr. Henry, for this informative overview of the guideline. Keeping these clinical practice guidelines updated is really crucial and it takes a lot of careful thought to ensure these recommendations represent the evidence. So thank you for coming on the podcast to discuss the "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you very much for the opportunity to talk with you today. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm a medical oncologist, and I'm a researcher at the University of Michigan Rogel Cancer Center. And I'm also the past president of the American Society of Clinical Oncology. Over the last and now the next several podcasts, I've been really privileged to be your host for a series of interviews with the people I feel are the founders of our field. Over the last 40 years, I personally have been fortunate to have been trained and mentored and I've also been inspired by many of these pioneers. And it's my hope that through these conversations. We'll all be equally inspired by gaining an appreciation of the courage and the vision and the scientific understanding and the anecdotes that let these men and women to establish the field of clinical cancer care over the last 70 years. By understanding how we got to the present and what we now consider normal in oncology, I think we can also imagine and work together towards a better future for our patients and their families during and after cancer treatment. Today, I'm really pleased to have my guests on this podcast Dr. Norman Wolmark, who was his mentor and longtime colleague, Dr. Bernard or Bernie Fisher, was responsible for the unbelievable success of one of the most influential cancer cooperative groups in the world, the National Surgical Adjuvant Breast and Bowel Project, or the NSABP, which of course, in recent years has now been merged with two other corporate groups to become the NRG. Doctor Wolmark as a professor of surgery at Drexel served as the executive medical officer from 1979 to 1994 during Dr. Fischer's leadership of the NSABP. And then he became the chairman and PI of the group until 2004 when he assumed the same role with the merger into the NRG. The NSABP is generally credited with what is now called de-acceleration of therapy, in particular of local therapy of breast cancer by applying the scientific method to compare a modified radical mastectomy to radical mastectomies and subsequent breast conserving treatment a modified radical mastectomy, as well as testing the concept of sentinel node mapping, which we now use routinely. NSABP was also one of the pioneer groups to test the value of adjuvant systemic therapy. They started with adjuvant chemotherapy, comparing L-phenylalanine mustard, or L-PAM to nothing in the 1970s, and later, tamoxifen versus nil. Other successes of the NSABP include one of the first trials or adjuvant trastuzumab. And further, NSABP was the first to report the prognostic value of the genomic test to guide the use of adjuvant chemotherapy in ER-positive breast cancer. Incidentally, it also conducted the largest and the most definitive set of studies of chemo prevention, first with tamoxifen versus nil, and then later, comparing raloxifene to tamoxifen. Not just breast cancer-- in gastrointestinal malignancies, the NSABP made seminal observations regarding radiation for rectal cancer and adjuvant chemotherapy in colorectal cancers. Dr. Wolmark himself has published over 300 peer reviewed papers, numerous other commentaries and reviews, and frankly, I started to list your honors, Dr. Wolmark, but I ran out of space. You've just had too many to count here. I think it is safe to say that the reduction of both mortality and toxicities related to breast and GI cancers over the last four decades, coupled with improvement on how we treat people, is in large part due to the brilliance and the courage and the hard work of doctors Wolmark and Fisher. Most importantly, I think they showed so many of us the importance of challenging dogma, for example, how study and thinking in breast cancer and applying the scientific method to clinical research and practice. [GASPING] I have to take a deep breath, Norm. Welcome to our program, and thank you for joining us. Well, thank you, Dan. I think after that glowing and complimentary introduction, which was far too generous, probably the most strategically sound decision that I could make is to thank you and to terminate this discussion, because I don't think that I can possibly improve on it. But I don't suppose that that's the purpose of this endeavor here. Yeah, no. People aren't tuning in to hear me. They're tuning in to hear you. And this is hero worship on my part. I want to start out with your background. I know you grew up in Montreal. You graduated from undergraduate, medical school, and later, you did your surgical training at McGill. What were the circumstances that your family was in Canada? And what got you interested in medicine and, specifically, surgery? Well, that's an interesting question. I did not grow up longing to become a physician. As a matter of fact, my interests at McGill, certainly during undergraduate school, included biochemistry. And I was in the honors biochemistry program and was going to pursue a career in nucleic acid research. And at the last moment, I had a change of heart and decided to go into medicine at McGill. And McGill was not an embracing environment for surgeons. I think surgery, certainly in our era, was regarded as a sub-medical species. And it wasn't until my internship and early residency that I embraced the possibility of developing and evolving a career in surgery. Was that attitude out of also having been at McGill-- long before you were there, I know, but most places were dominated by the surgeons. And then medicine came along after that-- Mayo Clinic, for example. Do you know? Was this an outgrowth of Osler's influence? Well, I don't know that it was an outgrowth of Osler's influence, but it was certainly difficult for us to escape Sir William Osler. I think at the graduation after our second year, we were provided with a leather bound copy of Aequanimitas, which of course, nobody read, because medical students are not interested in the history of medicine. It was only years later that I read most of Osler's non-scientific works. That's interesting. So then you went to Pittsburgh to do your surgical residency and then two years at the NCI and a year at Memorial. But then, you returned to Pittsburgh. Why Pittsburgh in those days? Well, what drew me to Pittsburgh in 1973 was my interest in clinical trials. And in 1973, there was a lot of excitement going on in clinical trials and breast cancer directed by Bernie Fisher and the NSABP. So that was something that attracted me, that one could apply the scientific method to evolve therapy. And this was something that I desperately wanted to participate in as a result of my background in basic research and biochemistry. So tell us about the heady days in the early '70s and even further back, if you'll recount sort of Dr. Fisher's history as well, of starting the NSABP. What was his vision? What was his plan? Why did he do that? How did you get involved? The whole evolution of cooperative groups and in particular, the NSABP, was an outgrowth of the initiative of the National Institutes of Health and more specifically, I think, to Bernie Fisher's mentor, IS Ravdin, at Penn. And that led to the creation by the NIH of the Cancer Chemotherapy National Service Center. And this was started by three surgeons and Michael Shimkin at the NIH, who was a medical oncologist, or what was then called a chemotherapist. And from that grew a number of disease-oriented initiatives called the surgical adjuvant chemotherapy projects for specific diseases, breast being one of them. And this was 1957. And by 1958, the NSABP had randomized its first patient. And certainly, Bernie Fisher was amongst the founders of the NSABP and then, of course, became chairman of the group in 1967 and moved it to Pittsburgh in 1970. What did it take to get a bunch of surgeons to believe that more than just surgery was important? The group started in a modest fashion. There were 23 institutions. And I think it's certainly an enormous credit at Bernie Fisher for demonstrating that a cooperative group could indeed be cooperative, with multiple heterogeneous surgeons joining under the rubric of the NSABP to evolve the state of the art breast cancer and challenge existing dogma. One of my first meetings, Dr. Fisher and Dr. Irvin of New York City were in a debate that I thought was going to get into a fistfight, with Dr. Fisher trying to explain the systemic therapy of cancer and that it was more than just surgery, and Dr. Irvin believing if you did super-radical mastectomies, you could cure more. You must have been in the middle of some of those discussions as well. I was, and remember them, and remember the acrimony, the hostility that existed at that time. As a matter of fact, there were societies that were created to counter the influence of the NSABP. The retreat from radical mastectomy was highly contentious. And of course, the debate of the two mutually exclusive hypotheses was certainly extant in Halsted's era. But Bernie Fisher determined instead of debating the issue to test the two mutually exclusive hypotheses using the scientific method, namely the randomized prospective clinical trial, which convinced surgeons that variations on the theme of operative nuance were not going to increase survivorship, that breast cancer was a disease with systemic components at its initiation, and the retreat from a radical mastectomy and the ascent of systemic therapy are inextricably intertwined. And they are so largely because of the efforts of Bernie Fisher and the NSABP. This is an interview with you, except that you know Bernie Fisher better than any of us-- who, incidentally, turned 100 years old in August of this year. What were the driving forces for him to think this way? Do you know? Was there a sudden aha that systemic therapy ought to be as important as the surgery? I know he did some preclinical studies to suggest this. Can you give us more background of what he was thinking and how he got there? Well, when I first joined him in 1973, it was a unique environment. There was a continuum between the laboratory and the clinic. And hypotheses were generated in the lab from murine models and applied to clinical research, which we now call translational research. And certainly, I think he was influenced in many ways by the preclinical work that he did in murine models on metastases and multiple other observations to challenge the sanctity of the radical mastectomy, which was based on the belief that breast cancer was a local, regional disease and spread in a logical, predictable, stepwise manner, again, along fascial planes. This, of course, to scientists, was something that did not stand up to a solid review of the data. Through the years, I've picked up many pithy comments from Dr. Fisher. One of them is that-- what was it? In God we trust. And for everything else, we like data, which I always thought was a great statement, something to that effect. The other was, you may be logical, but breast cancer is not. That really has stuck with me through the years, which is, it doesn't follow a logical string of linear progression. But rather, it becomes systemic, or it doesn't, which I think changed the field. Well, Bernie always challenged existing dogma that was based on empiricism. I think Bernie taught us to challenge the individual who ascends to the professorial pulpit armed with a retrospective case series. And based on personal charisma or the institution that that individual represented, such an individual was able to influence the way a disease was treated for decades and then close to 3/4 of a century. Challenging that dogma, insisting that therapy be evolved based on data rather than retrospective case series, I think, is a lasting contribution. He blazed the trail for the rest of us. Since you were there for a lot of this, how about some of the other luminaries of the time? Dr. Crile had a lot to do with the early thoughts that maybe you didn't need to do mastectomy. Can you enlighten us on some of the other folks that were some of the early pioneers in the field? There were certainly proponents of lesser operative procedures starting with [INAUDIBLE] and in the UK, Vera Peters, in Canada, Barney Crile, or George Crile, Jr. at the Cleveland Clinic. But again, these were based on anecdotalism. There were very few randomized prospective trials challenging the sanctity of the radical mastectomy. There were some-- Sir Hedley Atkins, the Guy's Hospital trial comparing breast-preserving versus mastectomy, a trial that had few patients and was reported, I think, in 1971 was a case in point. And then Umberto Veronesi with the quadrantectomy study, which was reported in 1981, preceded B-06. But certainly, B-06 had an enormous impact in 1985. And I think to Bernie's credit, he was able to convince his colleagues, even his detractors and his coevals of the value of breast preservation. But more importantly, I think he was able to convince surgeons of the biologic behavior of breast cancer with its systemic components. Yeah, I agree. I remember that paper. Actually, I remember most your papers. B-04 for was the predecessor. And of course, if there is a Rosetta Stone for the NSABP, it was comparing radical mastectomy to total mastectomy, which was a heroic trial to have initiated in 1971. If there is a bellwether turning point, it was B-04. This was the trial that truly compared the two mutually exclusive hypotheses to enormous, enormous resistance by the surgical community. And the paradox was that the 23 institutions that participated in the NSABP were run by surgeons. I came into the field in 1982. I have seen maybe three radical mastectomies in my life based on the fact that B-04 was beginning to change that whole field. And the three or four patients I saw had horrendous qualities of life because of that radical mastectomy. So I think our listeners, the younger ones, need to understand how courageous this was. Let me ask another question. I don't think you were part of it then, but as Dr. Fisher began to, then, think about adjuvant chemotherapy, why L-PAM? Most of the people listening to this probably have never heard of L-PAM, let alone used it. Why was that chosen as the chemotherapy to use in the first trial? Well, that's an interesting question. CMF was being developed at the NCI-- Paul Carbone, Vince DeVita, George Canellos. And L-PAM was an oral agent. And we speculated, sotto voce, of course, Bernie and I, that the reason the NSABP got L-PAM was that it was oral and could be given by surgeons, whereas the CMF, which was more difficult to administer, went to Gianni Bonadonna, who reported on the CMF data in the adjuvant setting a year after the L-PAM data were reported in 1975. Ironically-- correct me if I'm wrong-- but I think the relative benefits of both were almost identical. And the reason L-PAM fell out of favor was the secondary leukemias. Is that your perception? Well, L-PAM fell out of favor, certainly. We did L-PAM, then L-PAM 5-FU, then L-PAM 5-FU plus doxorubicin in a stepwise, sequential manner. I think CMF was embraced. Had there been a direct comparison earlier on, perhaps L-PAM would have had a role. But I think it faded away. And it faded away for us largely because when we compared CMF to four cycles of AC, which could be given in a much shorter time, there was no difference. So AC became the standard, certainly for us. Moving on a bit, as I've already-- another of Dr. Fisher's statements that I've lived on is that the hallmark of a good clinical trial is that it raises more questions than it answers. I love that because it means you have to keep thinking. Can you give us examples how you and Dr. Fisher started designing the next trial as the first one was starting to finish, and how that led, one way to the other? I've always been struck by the fact that the NSABP has been more linear in its trial design than most of the other cooperative groups. Well, it was a continuum. The next trial was based on the results from the previous trial or the anticipated results from the previous trial. A case in point, B-04, total mastectomy, where lymph nodes are not fulgurated, left behind completely untreated, compared to radical mastectomy, where they were removed. 40%, it turned out, of the total mastectomy group had histologically positive nodes. And yet, the outcomes were the same, which supported the use of systemic therapy, that patients were failing not because inattention to operative detail, but because they had systemic metastases. Well, you can ask, how did you transpose this data or know about this data to start your next trial? Well, in that era, the results were available to us in real time. We had a magnetic board, for example, for B-04, where every patient that was entered into the study, of course, anonymized, was on that board, and we could see the treatment failures in real time. So we had a pretty good understanding of what the results were when B-06, for example, was started, and certainly when the L-PAM trial was initiated. To us, in that era, alpha-spending meant buying a suit at Bergdorf Goodman. It's only later that these restrictions, appropriately so, were initiated. So we were able to be very nimble in transposing the data from one trial to formulate the hypothesis for the next trial. And that led to, I think, a very elegant, sequential, logical, stepwise series of trials, which I think in this era, could not be conducted. Did you ever get concerned that you were jumping ahead to the next trial with insufficient follow-up with the last one, and you'd get ahead of yourself in terms of unexpected toxicity showing up or, for example, in the deacceleration of therapy, that in fact, you were wrong, and then you had a bunch of patients that you had given less than enough therapy? I can't think of the fact that you have. But was that a concern as you were designing these? Every clinical trial is a concern. And yes, there was a concern. But we believed that we were basing these trials on objective data, data that were generated through clinical trials and the scientific method. So let me ask another question, because I was never in the NSABP, but I was always struck by the fact that your statisticians sat at the table and thought as much about the biology as they did the p-values. Do you want to talk about some of the statisticians you've had the chance to work with? Absolutely. I think that's an accurate description. Carol Redmond was the first statistician with whom I came in contact and was an integral part of clinical trial development, discussing not only sample size, p-values, interim analyses, but also the biology of the disease and what the biologic end points were going to be, and what the ancillary end points ought to be, and calculate appropriate sample sizes to answer these questions. We were very fortunate to have outstanding biostatisticians who were giants. Sam Weiand, who followed Carol Redmond, who was at the University of Pittsburgh, went to the Mayo Clinic, and returned to us around 1994, '95, and John Bryant, who was absolutely instrumental in the joint analysis for the Herceptin trials, B-31 and N9831, who was a driving force, and was certainly a driving force behind the development of the Oncotype DX genomic profiling. These weren't simply numbers people. They were colleagues. They were part of the assault on the hill. I have to jump in for two reasons. One is I never worked directly with John Bryant, but I can't say how many times I called him and said, what do you think of this? because I knew he would understand the biology as well as the statistics. I miss him dearly. He sadly passed away about a decade ago. As do I. The other is, as you know, we lost Jim Holland this year. My first presentation at CALGB, Dr. Holland was sitting in the back of the room and yelled from the back of the room, because he never used a microphone, not unlike my colleague on the line right now, by the way. Dr. Holland yelled from the back of the room, Hayes, if you need a statistician, it's not worth doing. And I said, well with all due respect, Dr. Holland, and there's a lot of respect here, I have to disagree with you. Did Dr. Fisher get along with the statisticians the way you have? Did he feel that this was a two-way street? Or were there times he said, my way or the highway? There's always robust dialogue and discussion. I think that both Bernie and I embraced our statisticians as colleagues. I have to be very careful. This was not unwelcome embracing. But they were always an integral part of developing and analyzing the protocol. And they were colleagues. And certainly, Bernie had that approach and philosophy as well. So let me, perhaps, describe in 1973, when I first arrived, what struck me as extraordinary. There was passion, excitement, drama. We weren't sure where we were going. But we knew we were getting there fast. And we embraced the journey, the quest. And that was an extraordinary time where we knew that the standard of care was going to be changed. We couldn't predict the outcomes, but we knew that what we were doing at the time would have a lasting impact on the field. Actually, that was my question, which was, did you realize what you were doing in the late '60s and early '70s was as exciting as it was? Sometimes, I think we're in the middle of something, and we don't realize how it's going to turn out. And you've just answered my question, which was it must have been years-- It was challenging the basic sanctity of the dogma, the tyranny that existed at the time. And that, in itself, was a courageous and extraordinary thing to do. And I have to say because of that work, and others, but we've seen a remarkable reduction in mortality due to breast cancer over the last 30 years, probably by more than a third, not quite half. And it's because of these kinds of challenges of dogma and courage to move forward. So I think we all owe you and Dr. Fisher and those who were involved in the early days, then also in the other groups, just an enormous debt of gratitude. My final question to you, Norm, and everybody asks this where did you get your style of presentation? I've argued, although I know you're Jewish, you could have been a Baptist minister. Where did this come from? I have no idea. Everybody loves it. Well, that's certainly very gracious of you, Dan. I've certainly, in the era of protocol B-04 and B-06, I have been summarily booed by an audience in unison. So that may not be a uniform perception. Well, I hope that our listeners who are driving to work or having their morning cup of coffee and listening to this have enjoyed it. I certainly have. Thank you for being so gracious and taking the time to do this. Thank you for all your contributions to the field and for mentoring so many, including myself, frankly. And I consider you a great mentor and a great friend. So I appreciate it deeply. Thank you, Dan. It's been my privilege.

Laurie was no stranger to cancer after she faced a bout with stage 3b non-Hodgkin lymphoma back in 1977, but her second diagnosis of breast cancer left her with a very tough decision on how she wanted to move forward with treatment. After her oncologist recommended she us a diagnostic test, called the Oncotype DX assay, that helps make informed, individualized treatment decisions, Laurie was able to forgo chemotherapy treatment when she received a recurrence score that indicated that she had a relatively low risk of her cancer returning. This week, we spoke with Laurie about her treatment decisions, and how this diagnostic test gave her what she calls “a piece of her life back.”

Host Cyrus Webb welcomes Dr. Ruth Oratz and Jennifer Merschdorf of Young Survival Coalition to #ConversationsLIVE to discuss options for breast cancer patients, what it's been like to share information on new treatment and what consumers should know about the Oncotype DX test.  Find ot more at www.mybreastcancertreatment.org and www.youngsurvival.org.

On this episode of SO Files, Alston, Brad and Linda take a closer look at the recently published TAILORx Clinical Trial Published in NEJM by Sparano and colleagues. The study expands the existing clinical application of the Oncotype DX score. If that score sounds familiar its because it has been making its way into clinical practice over the past few years (see our last episode on the new AJCC guidelines!). We explain the origin of the score, how it has been incorporated into clinical practice thus far, and how this trial addresses a large gap in the existing literature.

The TAILORx study demonstrated that most women with a specific early-stage breast cancer and midrange score on the Oncotype Dx test do not need chemotherapy after surgery. These findings will spare thousands of women from the harmful effects of chemotherapy. We spoke with Andrew Paramore from Genomic Health (CA, USA)to discover insider details of the trial and what’s next for TAILORx.

Dr Kaklamani talks to ecancertv at SABCS 2015 about results from the ongoing, prospective Trial Assigning Individualized Options for Treatment (TAILORx) involving more than 10,000 women with estrogen receptor (ER)-positive, HER2-negative, axillary node-negative breast cancer. TAILORx has been designed to demonstrate whether the Oncotype DX can be used to correctly identify women who may not need chemotherapy and could safely be given endocrine treatment alone. In the study, patients with a low (25) RS assigned to chemoendocrine therapy. Women with an intermediate (11-25) RS were treated with chemoendocrine therapy or endocrine therapy alone and results of that study arm are expected in the future. Dr Kaklamani discusses the data from the low risk group who received endocrine treatment alone. Five-year rates for distant relapse-free interval, the relapse-free interval, invasive disease free survival, and overall survival were a respective 99.2%, 98.5%, 93.7%, and 98.2%. The findings show that despite meeting guidelines for recommending or at least considering adjuvant chemotherapy based on classical clinical and pathological features, the risk of recurrence was very low at 5 years. This population of women patients may be very effectively treated with endocrine therapy alone without chemotherapy.

BreastCancerUpdate.com/ThinkTank – Proceedings from a Clinical Investigator “Think Tank.” Oncotype DX Assay. Interviews conducted by Neil Love, MD. Produced by Research To Practice.

Most patients with ER-positive, HER2-negative, node-negative breast cancer should be presented with the option of participating in the TAILORx trial and of having the Oncotype DX assay performed outside of a trial.