8 Days After the FDA: Breaking Down HRT and Breast Cancer Risk

Preventative HealthBreast Cancer RiskHormone Replacement Therapy (HRT)Human Health XX (Women's Health)
Written By Sharon Kedar

about the episode

On this episode of Innovate & Elevate, Sharon sits down with Dr. Corinne Menn, an OB-GYN, menopause specialist, and breast cancer survivor, to unpack one of the most misunderstood topics in women’s health: the relationship between breast cancer risk and hormone therapy. Recorded eight days after the FDA announced it will remove the long-standing black box language on hormone therapy, this conversation traces the legacy of the 2002 Women’s Health Initiative press conference, what the data actually showed, and how modern evidence can better guide women and their clinicians today.

What You’ll Learn from this Episode:

  • - What really happened in July 2002, and why the WHI press conference (held eight days before doctors saw the full study) reshaped hormone therapy for a generation.

  • - The difference between estrogen alone and combined estrogen–progestin therapy, and why age, timing, and formulation matter.

  • - Why every major professional society (ASCO, ACOG, American Urological Association, The Menopause Society) agrees that local, low-dose vaginal hormones do not increase breast cancer risk, recurrence, or mortality.

  • - The role of tools like the Tyrer–Cuzick breast cancer risk model in understanding your baseline risk - and how Dr. Menn interprets those results in the context of HRT.

  • - Dr. Menn’s own story: being diagnosed with ER/PR-positive breast cancer at 28 during OB-GYN residency, going through abrupt menopause, and later discovering a BRCA2 mutation after updated genetic testing

  • - How she now counsels breast cancer survivors about menopause, quality of life, and when hormone therapy may or may not be appropriate
    - Practical ways women can prepare for a time-limited doctor’s visit to have more informed, individualized conversations about breast cancer risk and hormone therapy

About Dr. corinne menn

Dr. Corinne Menn is a board-certified OB-GYN and nationally recognized menopause specialist with more than two decades of clinical experience. A breast cancer survivor herself, she brings a unique blend of medical expertise and lived experience to her work, helping women navigate menopause, breast cancer risk, and hormone therapy with clarity and compassion. Dr. Menn is certified by the North American Menopause Society and serves as a clinical educator on midlife women’s health, breast cancer survivorship, and evidence-based hormone therapy.

Connect with Dr. Corinne Menn on LinkedIn, Instagram or her website.

Episode Outline

00:00 – Local Vaginal Estrogen and the Black Box Barrier

01:00 – Introducing Dr. Corinne Menn and the HHS Moment

02:00 – What the FDA Label Change Actually Means

04:00 – The 2002 WHI Press Conference and Its Fallout

06:00 – Dr. Menn’s Personal Story: Cancer at 28 and Abrupt Menopause

09:00 – Modern HRT vs. WHI Formulations

13:30 – Time-Limited Visits and the Need for Prepared Patients

21:00 – Knowing Your Baseline Breast Cancer Risk

29:00 – Does HRT Cause Breast Cancer? What the Data Actually Show

36:00 – Breast Cancer Survivors, Choice, and Quality of Life

  • Dr. Corinne Menn: Every single professional medical society that cares for these women, ASCO (American Society of Clinical Oncology), American College of OB-GYN (Obstetricians and Gynecologists), American Urological Association, the Menopause Society, all have clear guidelines that local safe vaginal hormones do not increase your breast cancer risk.

    You don't get breast cancer from it, and you don't get a breast cancer recurrence from it, and it doesn't impact breast cancer mortality. Let's face it. If I sit here and spend a lot of time with a patient and I counsel her and how we can help with her GSM. And she feels confident, and then she goes to the pharmacy to pick up a prescription, and then she looks at that inner label and she goes, oh, but Dr. Menn, like it says breast cancer, and I've already had breast cancer. I'm so afraid of it coming back. Why would you prescribe me this? I know you explained it to me, but this label scares me.

    This is something simple and easy that we can prescribe for patients that we've got safety data on. And this label was part of the barrier.​

    Sharon Kedar CFA: I'm so happy to have Dr. Menn on today.

    Dr. Corinne Menn: Thank you for having me.

    Sharon Kedar CFA: Just to catch the viewers up. I first met Dr. Menn when I gave her an "I ♥️ HRT" pin at Tamsen Fadal's house for Dr. Vonda Wright's Unbreakable book party. Dr. Menn is uniquely qualified. She is an OB-GYN, a menopause specialist, and a breast cancer survivor herself. So we are going to go into the discussion about breast cancer and HRT. We are eight days after we saw each other at the Department of Health and Human Services (HHS) where we witnessed history. We were there with two of our good friends,

    Dr. Rachel Rubin, who's also my personal doctor, Dr. Kelly Casperson were on stage with Secretary Robert F. Kennedy Jr. and with FDA Commissioner Dr. Marty Makary. It was a really big deal in terms of evolving the black box warning, which has been on hormone therapy for over 20+ years.

    And why I'm excited about today is, I think that women deserve to have the educated conversation. They deserve to have choice. This is good for them and their families.

    Dr. Corinne Menn: What's so significant about eight days?

    Eight days from the announcement that the FDA is no longer going to require a black box label on local vaginal hormones, as well as on systemic hormone therapy. The label is still gonna be there, right? We still have drug inserts and we still have information, but the information is going to be individualized and nuanced to the product. So vaginal hormones will emphasize the use of vaginal hormones for the genitourinary syndrome of menopause (GSM), which is really important 'cause so many women have avoided using safe local vaginal hormones because of the fear in the insert. And then with the systemic hormone therapy, the drug companies will petition and ask for new updated language.

    And the FDA is going to require that the language includes data from the Women's Health Initiative that shows younger women, between 50 and 60 starting hormone therapy, showing those benefits versus risks and making it more clear.

    But I was kind of asking a leading question 'cause I have so many questions for you and just thank you for your work. But the book Estrogen Matters from 2018, 7 years ago. It unpacks the information that wasn't accurately shared with women and their families.

    Sharon Kedar CFA: So back in 2002, there was a big splashy, some call it melodramatic, press conference that announced that they were halting this very large, very expensive, and actually really important study. I don't want to throw the baby out with the bath water. We learned a lot from that study.

    Dr. Corinne Menn: But the press conference really overemphasized risks, underemphasized benefits, did not provide any nuance in terms of age of initiation of hormone therapy, or that the things that they were seeing and reporting on simply did not apply to those with premature menopause or even to those who were just starting it within the first 5 to 10 years of natural menopause.

    And it didn't give any information about the nuances between estrogen alone, plus estrogen with a progestin. The news media ran with it. But you're alluding to the eight days. It wasn't until later that the doctors actually got to see the real study because this was before the internet.

    And so no one was able to just click on the link. So there was a press announcement, but you couldn't learn as a doctor what was behind the press announcement.

    Sharon Kedar CFA: I'm a lay person, right? Just for the lay people who are listening, is it typical or not typical?

    Dr. Corinne Menn: That's not typical. We look for peer reviewed journal articles, right? Meaning that you submit it to a publication and then your peers at that journal review it and then publish it. So that was done, but the press conference was before anybody could actually read the article. And so the problem was that physicians who were in practice had all of these patients calling them because they heard on the Today Show or CNN or The New York Times or Time Magazine that HRT causes breast cancer. Get off of it.

    Sharon Kedar CFA: Breast cancer is impactingI imagine for everyone in the audience, given the statistics, that this is personal to you, so we are not taking this lightly. If you could introduce yourself, Dr. Menn, just share a little bit about your own story and your background.

    Dr. Corinne Menn: Speaking of the WHI and the black box label, which this all started back in 2002 when the WHI study on hormone therapy was halted suddenly. And when I look back to where I was in 2002, I was in the middle of chemotherapy for an early stage breast cancer. I was a second year OB-GYN resident. And in December of 2001, I was diagnosed and through that journey of treatment, I was plunged into abrupt, premature menopause. And so I don't remember the WHI announcement, right?

    Because you know why? I was in my program director's office around that time saying I needed to take a leave of absence.

    But the leave of absence was not necessarily from the chemotherapy itself or the trauma of the breast cancer diagnosis, which was certainly really hard. But looking back, it was because I was totally unprepared and nobody helped me with the abrupt menopause that I was thrown into.

    I had horrific hot flashes and night sweats, terrible insomnia, new onset of anxiety and depression. And yes, all of these things were certainly also impacted by the cancer and the stress of that, et cetera. But it wasn't until really years later, when I went through a permanent surgical menopause 'cause my first menopause experience was temporary and then ovarian function returned when treatment ended.

    It wasn't until then that I looked back and I realized that I was not prepared to take care of the average woman seeking menopausal care or considering hormone therapy 'cause

    I don't even know if I ever wrote a prescription for HRT during my residency, because as a second year resident, that's when the black box label got put on. And so it wasn't until years later that I realized I needed to be more prepared to not only help patients, but also to help the most vulnerable women like myself; those who were dealing with an abrupt menopause or premature menopause. And we can certainly talk about that. For certain patients, HRT is not recommended. We can't use systemic estrogen for everybody, but what my experience taught me is that we still have to take care of these women, regardless of whether they can take hormone therapy or not, and that we can always give them local low dose vaginal hormones, which that point is why I am here with you, because the fear that was driven into all of society around the world over estrogen causing problems, cancer, causing heart disease, et cetera, was applied across the board to all patients regardless of age and regardless of formulation, leading to a generation of women being denied access to it, but also a generation of cancer survivors, breast cancer survivors, women who are at high risk of breast cancer, being afraid of even safe local vaginal hormones. And these formulations were never shown to have any increased risk of breast cancer.

    Dr. Kelly Casperson and Dr. Rachel Rubin really highlighted this eight days ago when they presented to the public at this press conference. And I also wanna shout out Dr. Heather Hirsch and all the other doctors who showed up in the summer at the (FDA Menopause) panel. And they were really expressing that the genitourinary syndrome of menopause, which is vaginal dryness, pain with sex, urinary tract infections, urinary frequency and urgency, vulvar atrophy. We call it GSM for short. So local safe vaginal hormones, we've got many data points on their safety in the average woman, as well as in estrogen receptor positive breast cancer patients, right? We've got lots of data on this, right?

    Every single professional medical society that cares for these women, ASCO (American Society of Clinical Oncology), American College of OB-GYN (Obstetricians and Gynecologists), American Urological Association, the Menopause Society, all have clear guidelines that local safe vaginal hormones do not increase your breast cancer risk.

    You don't get breast cancer from it, and you don't get a breast cancer recurrence from it, and it doesn't impact breast cancer mortality. Let's face it. If I sit here and spend a lot of time with a patient and I counsel her and how we can help with her GSM. And she feels confident, and then she goes to the pharmacy to pick up a prescription, and then she looks at that inner label and she goes, oh, but Dr. Menn, like it says breast cancer, and I've already had breast cancer. I'm so afraid of it coming back. Why would you prescribe me this? I know you explained it to me, but this label scares me.

    This is something simple and easy that we can prescribe for patients that we've got safety data on. And this label was part of the barrier.

    Sharon Kedar CFA: As we both well know, it takes 17 years for updated guidelines to actually show up in the doctor's office.

    I am not at all saying that all women should be on it, but I mean, if people understand what you're talking about in lay person's terms are basic things like UTIs, where the alternative is antibiotics.

    So I'd like to sort of frame up the significance of where we are and unpack. 'Cause HRT is like saying a name of a restaurant without getting into the menu. Like there is a menu here. and so this book Estrogen Matters. Avrum Bluming and Carol Tavris wrote it. The intro was called What Killed HRT? The history here is we went from 1995, where the head of NIH, Bernadine Healy basically talked about how heart disease, stroke, osteoporosis, Alzheimer's disease may well be reduced by hormone therapy. And then literally the next page is July 9th, 2002, where it says seven years later, " The National Heart, Lung and Blood Institute of the NIH has stopped early the Women's Health Initiative, a major clinical trial of the risk and benefits of combined estrogen and progestin in healthy menopausal women, due to an increased risk of invasive breast cancer." So let me pause there and ask, can you just share a little bit about where that led us?

    Dr. Corinne Menn: This study was designed to really be a cardiovascular risk-benefit study. The primary outcome was not breast cancer. The primary outcome was, did hormone therapy prevent heart disease? They enrolled women the average age, roughly 63 or 64, but the age ranged quite high up until the late 70s even. These women were, on majority, more than 10 years from their last menstrual period.

    They were well into menopause, right? I think anybody understanding these basic facts can understand that heart disease, atherosclerosis, cholesterol being elevated, other risk factors for heart disease and blood clots, diabetes, cognitive changes, dementia, all increase as we age. Forget about menopause, just as we age.

    So if you start a study and you enroll women who are mostly in their 60s and beyond, to see if you can prevent these things when we know that they've already started, right? We know this, and actually we've known this for a very long time, that the menopause transition is a time of cardiovascular disease risk acceleration.

    And remember, these formulations that were used in the WHI is oral conjugated equine estrogens, and oral medroxyprogesterone acetate (MPA). I'm not gonna vilify these options. I actually think conjugated equine estrogens could be a really important hormone therapy option for some women. But we don't generally use them in modern hormone therapy in most patients. And we generally would not start oral estrogens in an older woman because we just know that it increases blood clotting factors.

    So of course if you start it in someone who's already got risk factors for clotting, like maybe they're heavier, maybe they have diabetes or other things, yeah, you're gonna have an increase in blood clots in venous thromboembolism. And the medroxyprogesterone acetate is a synthetic progestin. Again, we use it very often in GYN.

    It can be really good for helping control bleeding and protecting the lining of the uterus. But in general, we know that it increases breast density. It is a little bit more inflammatory. It's not the ideal progesterone because it's not progesterone. We've learned a lot from the WHI, but we've learned that the modern formulations that we use now, which is generally estradiol, and often in a woman who is maybe at a higher risk for cardiovascular events, we would use a transdermal estrogen, which is incredibly safe for most women.

    And then we pair it, if they have a uterus with progesterone.

    Sharon Kedar CFA: I asked your colleague,

    Dr. Sharon Malone, we were together at HLTH. And I asked her, I'm like, do we ever outgrow menopause? And so, just to remind folks, that if you are born with XX human biology versus XY. XX means you have an extra X chromosome, you're born female, you cannot escape menopause.

    And it's defined as 12 months without your period. The really tricky thing is it's not like hair loss. It kind of like sneaks up on you.

    And 10-15% of your bone density can go away.

    But there's not an alert. If you could just with that context to share more about what you were saying about transdermal estrogen.

    Dr. Corinne Menn: Yeah, so it's just important for people to know there's lots of different FDA-approved formulations of HRT, or we often call it MHT, Menopausal Hormone Therapy. The reason why we say that is just that in menopause, we're really not trying to replace high levels of hormones. We're giving menopausal hormone therapy in order to prevent osteoporosis, treat hot flashes and night sweats, which then in turn has all of these downstream effects.

    Like it helps with, you're not having hot flashes and night sweats, you're gonna sleep better, right? You sleep better and you feel better overall. You're gonna have less brain fog. You're going to feel better during the day. So then, you can actually do all the lifestyle things that we know are key to preventing chronic disease like exercise, nutrition, et cetera, right?

    It's all part of the package. Nobody is saying that all women must be on HRT. Nobody is saying that all women are candidates for HRT, or that HRT will cure all your problems or prevent all disease. But we must be honest with women that we have something that has been FDA-approved in various formulations: oral, transdermal patches, sprays or gels, different forms of progestin or progesterone. And we can find a safe, individualized option for you most of the time. And that for the vast majority of women, the benefits are going to outweigh the risks when we initiate it within the first 10 years of entering menopause.

    So that's just like the big key sentence there, right? Most women. If you can't use HRT, you are not doomed. But getting back to the formulations, in the Women's Health Initiative, they were using this one formulation and it's not all bad; there's good things about those formulations.

    But most of the time these days, we do use a transdermal. And when you take something orally, your liver has to digest it. And that oral estrogen can stimulate some clotting factors. That's generally not a concern for the younger woman who doesn't have any cardiovascular disease risk. But for someone who's a little bit older or has some other risk factors, the transdermal estrogen does not do that.

    And so it doesn't raise clotting factors. It's very, very safe. So the problem, getting back to the label is the label talked about risks, but as only as it really was demonstrated in older women using an oral synthetic progestin with this oral conjugated equine estrogen. So it's kind of like comparing apples to oranges and giving the same warning to everybody.

    And so, moving forward, we're just all excited about trying to teach more clinicians and patients and Alloy health professionals as well, so that they can inform the patients that they see that women deserve a nuanced, intelligent conversation about modern hormone therapy practices and how it's really should be a shared decision making and a choice with a woman.

    Only 5% are using it, but I think it's because most are not even given the option or told the benefits.

    Sharon Kedar CFA: In 2024, Harvard had asked me to do a panel with the Head of Women's Health at Harvard, who's a good friend of mine. And I couldn't sort of unhear what I heard when it comes to some of the disparities in some of the areas where we don't understand the science.

    So, when I did season one, I did three episodes on breast health.

    How the heck are we supposed to have a 10-minute doctor visit conversation when women today, by and large, don't know their lifetime risk factor for breast cancer?

    So now we're compounding it with an HRT conversation, which typically involves, and you'll correct me if I'm wrong: estrogen, progesterone, testosterone if you're lucky, vaginal estrogen, which is sort of the highlight of today. But how do you fit that into a 10-minute doctor visit?

    Dr. Corinne Menn: You don't.

    Sharon Kedar CFA: Okay.

    Dr. Corinne Menn: Listen, this is really important that we support doctors. 'Cause there's a lot of criticism that, oh, my doctor doesn't talk about menopause. Or, my doctor didn't inform me about this. But honestly, in defense of doctors,

    Sharon Kedar CFA: In a typical practice for an OB-GYN or a primary care doctor or a medical oncologist, really anybody. They are packed all day, 10-15 minute appointments. So much pressure on them to pack stuff in. And now we're asking doctors to provide even more care, right?

    Dr. Corinne Menn: So, I understand the pressures that doctors have, and that's a whole other topic. It's super toxic for physicians, right? And this is why as a patient, you really, unfortunately, there's a huge burden on you. You must be educated, you must be informed, and you must be prepared for your appointments. And understand that an annual visit is probably not going to be the time where you're going to want to have a nuanced conversation.

    Sharon Kedar CFA: My brain just exploded.

    What you just said is the PSA.

    Where is an average person supposed to go? People do not realize that they need to come in educated. It is unfair to assume that doctors have this all figured out. This is not like a broken bone.

    Dr. Corinne Menn: But listen, menopausal hormone therapy, this is not rocket science. The reality is the doctor is not informed. But even if the doctor is informed,

    because I've got a lot of excellent colleagues who are still practicing in an insurance-based model. They're seeing a ton of patients.

    And the patients come in for the annual exam and we need to do things like their breast exam and their pap smear and talk to them about preventative screenings to do hereditary cancer screening. We could talk about all the things we need to do for breast assessments, et cetera, and fit all of that in and answer questions and then counsel them on risks, benefits, alternatives, whether they're a good candidate to hormone therapy.

    You can't fit it all in into your annual exam. But the problem is, is patients wait months for their annual exam and then if they wanna follow-up, then they're gonna have to wait more months for it, right? If the doctor even has room in her schedule.

    So then you've gotta get a referral and you're gonna have to wait months and months and months . So that is a huge problem. It's one of the reasons why I do telehealth. I work with Alloy Health, and we have OB-GYNs in all 50 states. So we're complementing the GYNs of the primary care doctors.

    We're not replacing them. We're trying to provide access to evidence-based care for these women because we have a problem that we have to solve. There is an increasing demand for this care and doctors just don't have time or they don't have the clinical training to provide it. So I'm glad the black box label is removed.

    The next problem is now we've got to educate all of these clinicians. And it's very hard for women to even access basic primary care.

    Sharon Kedar CFA: Yeah. In some ways the FDA removal of the black box warning helps to uplevel to science and remove a part of the fear factor, but it does not change the reality that there's massive fear for over 20 plus years. And even before this announcement, we've been trying to educate doctors on the latest science, and it's not their fault.

    But the reality is that there's just a huge gap. And so where do you think women should go? And I think about what Dr. Vonda Wright said that she wants 30 something year old women to really get ahead of this.

    So when we say like, where does a woman go? There is the 30-year-old, there's the 40-year-old, 50, 60, 70, 80. Where does someone go?

    Dr. Corinne Menn: The first thing is, as a woman, you have to take ownership and control over your health. You cannot outsource this and just assume that you're being given the best information from your routine primary care doctors, right? Even with the best intentions, it's not enough. So where do you go?

    You have to go to trusted sources to get basic evidence-based information on your body, the physiology of perimenopause, of menopause, what your options are, what you can do to get ahead of things. And relating it to say the breast cancer risk.

    We're not even doing a great job of capturing the women early to identify who is at an increased risk and who would benefit from increased screening. The breast cancer risk assessment is intricately linked to the fears around hormone therapy. I always say that the fear of breast cancer is the driving force behind medical decisions by doctors and patients when it comes to how they're going to manage their menopause.

    And there's a lot of misinformation there. So I tell doctors and patients know your baseline risk of breast cancer and your baseline risk for other chronic disease: osteoporosis, dementia, heart disease. What's your baseline risk?

    Sharon Kedar CFA: What baseline risk test do you recommend?

    Dr. Corinne Menn: This is what the recommendations are. By the age of 30, really even earlier, 25. Women should start to talk to their doctor about, what's my baseline risk of breast cancer? And your risk is gonna change over time, right? So for instance, a younger woman should know some basic things, like how old was she when she started her periods?

    Does she have a family history? Look at both sides of the family; mom's side and dad's side. And go back a couple of generations and ask not only about breast cancer only; ovarian cancer, pancreatic cancer, prostate cancer, melanomas, different cancers. So that's one thing that women should know and understand that your family history evolves and changes, right?

    You should update your family history with your primary care doctor because there might be a new red flag just developed, and that might mean something. And then, as we get a bit older, there's other risks that might get incorporated to this. So there's a lot of risk assessments out there.

    The primary one that I would recommend is something called the Tyrer-Cuzick, right? Which is really important because it's a bit more nuanced than things like the Gail model, which not been validated for other women. And it likely slightly overestimates your risk, but it will give you a more short term as well as a long term risk of developing breast cancer.

    Sharon Kedar CFA: I've been trying to figure out a better answer for early detection. Please get your mammograms. That's our first line right now.

    But I've been trying to figure out like, how do we do better.

    Dr. Corinne Menn: So mammograms for the average person, for the average risk woman starts at age 40. So part of what we're talking about is risk assessment is earlier, because we wanna identify the high risk people earlier than 40 because some of these women would qualify for earlier screening.

    They might qualify for genetic testing. So that's really important and the Tyrer-Cuzick can do a good job at that.

    Sharon Kedar CFA: How old were you when you had your breast cancer?

    Dr. Corinne Menn: So I was diagnosed when I was 28. I felt the lump myself. I dismissed myself for four months 'cause I thought I was too young for breast cancer. I was also just too busy being an OB-GYN resident to actually be a patient myself. So a number of colleagues and even my own GYN says, let's just watch it for a couple of cycles.

    You're too young. It's probably a cyst. It's probably fibrocystic breast changes. Around the same time my mom had been diagnosed with stage four ovarian cancer. And so a few months later, she died ovarian cancer in November of 2001, and the day of her funeral, I came home and I was like, damn, this lump is still there. I should probably get it checked out. It took another month for me to finally do it with my call schedule and all this stuff, and I really wasn't scared. I mean, looking back, I was clueless. And right before the holidays in 2001, I was diagnosed with stage two ER/PR positive breast cancer, and initially was tested negative for the BRCA mutation.

    We did not have a family history of breast or ovarian cancer. I had a mastectomy on one side, did chemo all my treatment, the premature menopause, all the insanity. Later on, decided to go back and have the other breast removed prophylactically the following year, even though I did not carry the mutation.

    Fast forward years and years and years later. And this is why you have to be a squeaky wheel. I demanded retesting and follow-up genetic testing, and I do carry the BRCA2 mutation. But nobody told me to get updated testing. Nobody encouraged it. In fact, when I brought it up, they said, oh, you don't need that.

    Sharon Kedar CFA: What do you mean that it basically, it was a higher sensitivity specificity...

    Dr. Corinne Menn: So before 2013... This is really important for people to hear this. Before 2013, genetic testing for the BRCA gene did not include the full rearrangement analysis of the BRCA mutation. So the full rearrangement is now standard on most tests, which you wanna make sure. And it includes something called the Large Rearrangement or the BART sequence (BRACAnalysis Rearrangement Test), BART. In addition to that, since 2013, 2014, we now do panel tests and that's evolved as well.

    And it does evolve every number of years where there's other genes. It's not just BRCA. So I'm a living example of, I dismissed my breast lump. I wrote it off, the doctor says, you're too young. Fine. I finally pushed, I got diagnosed. I pushed to get the BRCA test. They weren't even encouraging it in me because we didn't have any breast cancer family history, although my mom died at 54 and I was 28.

    I was like, hello, red flags. And finally I got genetic testing after my initial mastectomy. And it was negative. And so I just believed it and it was negative at the time. I'm not blaming the doctors. That's what the test was done. But someone should have recalled me. Like I shouldn't have had to be doing continuing medical education on my own and finding, oh wow there's update testing.

    I need to do this because I was still being seen by my doctors, right? Nobody told me to get updated testing. And so when you talk to women who say they have a family history, they're like, yeah, but my mom had that test when she had her breast cancer. But like, when was that?

    She was like, oh, I don't know, in 2004, 2009. So you need update testing, right? If you had your test after 2014 or so, you're probably okay. But it doesn't harm to just be like, hey, can I see my results? And maybe let me just check in with my genetic counselor.

    Sharon Kedar CFA: That field is evolving quickly. A ton of genetic breast cancer that we just don't have the test yet for. So that's a lot of medicine we just don't have the diagnostic test.

    Dr. Corinne Menn: But remember most, I don't want people to listen to this and think that if I don't have a family history or I don't care a mutation, I'm not at risk. Most women who get breast cancer don't have a significant family history. And most women who get tested genetically do not carry it.

    It's like 10 - 15% max percentage. So most women are just like this "average population", but there are other risk factors. Breast density, previous breast biopsies. Patterns in childbearing and breastfeeding, et cetera. There's lots of factors. So this is why we want to routinely check in on these factors to see who could get earlier screening, even if they don't carry a gene, right?

    That's important. Now, one thing I wanna point out that's tied to the Tyrer-Cuzick and to hormone therapy, and this is really important and maybe I'll get some pushback on this, but when we look at the different inputs in the Tyrer-Cuzick risk calculator, breast density, family history, your menstrual history, , if you've had breast biopsies, what they were, et cetera.

    There's a lot of things that go into it. One of the questions is, have you ever taken hormone therapy.

    So I pushed and dug and figured out like, where are they getting the source data in the Tyrer-Cuzick model to make predictions of breast cancer risk based on HRT. And it's unbelievable. It's large epidemiologic study data, but it doesn't include even the WHI data. So if you could take the least reliable data, like large epidemiologic observational studies, that's what they chose to use for this model.

    If it did reflect the WHI data, it would give you actually even a more accurate result because the WHI data, women who were taking estrogen alone had a lower risk of breast cancer and a lower risk of dying of breast cancer. And worse case scenario, this is randomized controlled study data, right?

    Like this is gold standard. The combined estrogen and synthetic progestin data from the Women's Health Initiative, while it did show an increased incident of breast cancer detection, which was not statistically significant, but let's take it at face value, it did not show an increase in breast cancer mortality.

    And we know from subsequent data that the risk is likely very different depending on the formulation. And that progesterone appears neutral. So when all these women are now gonna take this Tyrer-Cuzick and plug into their HRT, I'm telling you it bumps up your lifetime risk. And it can scare women. It'd be like, oh, well I should get off this HRT, right?

    So what I do is I do the Tyrer-Cuzick without plugging in the HRT. I get their baseline risk. And then I say, for you, based on your baseline risk, this is how I would interpret giving you these various formulations of hormone therapy. And I think that's a much more intelligent and wise way to do it.

    Sharon Kedar CFA: Just to be clear also on your point, and so what Dr. Menn is saying is, use the test if you have the privilege of having a doctor like her, she's giving you an option for how to increase the accuracy. But if we also just talk about, and I'm very pro knowing, no test is perfect, all of these things.

    So if you're gonna use it or not use it. But also what is HRT? Because to your point, it's a question, but it doesn't ask: are you on estrogen? Are you on progesterone? Are you on vaginal estrogen? Testosterone is part of HRT, but it doesn't unpack that.

    And a woman who is on vaginal estrogen to protect against UTIs, versus a woman who's on systemic estrogen. it's not specific enough a question for something that really matters.

    If I could take it one step further and ask you, does HRT cause breast cancer? Did it cause it in the WHI and what conversation do we want women to have?

    Dr. Corinne Menn: It doesn't cause breast cancer. In the Women's Health Initiative, the estrogen alone arm of the trial, that was conjugated equine estrogen. So that's the formulation we could specifically say this data was shown to decrease the risk of being diagnosed with breast cancer, and it decreased the risk of breast cancer mortality, and that was shown at the 20-year follow-up.

    So that's estrogen alone. So when people say, oh, estrogen causes breast cancer, I'm like, did you actually read the WHI data? Because the WHI data showed that actually estrogen alone decreased it. Now, to be totally accurate, it's really important to say, conjugated equine estrogen - that's what the study used, right? We've got the best data that conjugated equine estrogen alone decreases the risk of not only incidence of breast cancer, but death of breast cancer. And this is in women who don't have breast cancer. Okay? Like we gotta put breast cancer patients in a different bucket when you talk about it.

    Subsequent smaller trials, observational data, other data points, show that estradiol alone appears to also have that lowering of incidents, right? So critics will say, no, you can't say estrogen lowers the risk of breast cancer 'cause it was just CEE (conjugated equine estrogen).

    But we can say the totality of evidence right now that we have is that yes, great data on CEE, and lots of data points that suggests that estradiol alone also does that. And then when I say, if you have a uterus and we're going to use a progestin, a synthetic progestin, which I rarely prescribe. I will tell them, this is what the WHI showed a non statistical significant increase of less than 1 additional woman for every 1,000 women using it, in breast cancer diagnosis, but not breast cancer mortality. And subsequent data, not quite as robust, not as large, unfortunately. But subsequent data points suggest that when we use a progesterone, like a bioidentical FDA-approved micronized progesterone, it appears neutral: that it does not increase the breast cancer risk. That's the data we have.

    That's how I counsel my patients, that formulation matters and that even if we accept a slight increased risk of diagnosis, looking at the WHI data, it showed that it was largely driven by this increase in breast density. Okay, really important. And so what do we know?

    We know that medroxyprogesterone acetate (MPA) increases breast density. Hence why we've moved towards progesterone, which has less of effect on breast density. Not a zero effect, but much less of effect. And then we can go even further and know that we've actually evolved. We even have something called Duavee, which is conjugated equine estrogen, which remember lowered the risk and it's paired with a medication called bazedoxifene, which is a SERM, or selective estrogen receptor modulator, where it blocks estrogen receptors in the breast.

    So when I have women who are really high risk of getting breast cancer; very, very dense breasts, really strong family history, a BRCA previvor who maybe still has her breasts and has not had a prophylactic mastectomy. If they've lost their uterus alone, I'm gonna be really happy giving the estrogen alone.

    We've got data to show that even those women have a lower risk of ever getting breast cancer if they use that. But if we've gotta use a combined product to protect their lining of the uterus, I really love Duavee. So that's a great option and I am not afraid to give them estradiol or progesterone. But I don't want women to fear learning their breast cancer risk out of fear that they're going to be told no to hormone therapy.

    You could have your cake and you could eat it too. We wanna know your risks so that I know what kind of surveillance, how often should we do your breast cancer screening? You know, should we use a mammogram with an MRI. Do you qualify for that? If you have a greater than 20% lifetime risk, you do. We can do two things at once.

    We can also treat your menopause symptoms.

    Sharon Kedar CFA: This is just such an important conversation and, if I read Estrogen Matters correctly, when it talked about, it's not estradiol, it's horse estrogen, and it's not progesterone, it's a progestin, which is synthetic.

    But when it talked about the increased risk of one in a 1,000 patients, I read that there was this "dirty placebo group." What's your opinion about the placebo group that they had been on HRT and so that might've reduced their risk of breast cancer, which then showed this statistically insignificant gap with the control group.

    Dr. Corinne Menn: So this is a really important point, and this has been a criticism of the data for literally as long as the WHI data has been out. But just to try to make it simple. So for women in the placebo arm of the combined estrogen plus progestin, those women, 'cause remember these women were older, right?

    And these were not like mostly 51 year olds. These are women in their mid 60s and beyond. Many, many, many of them had used hormone therapy in the past. So when you look at this group of women who were taking both an estrogen and progestin, and you look at the women in the placebo group, a large number of them at some point in time had used hormone therapy, right?

    The placebo group's baseline risk of breast cancer was strangely lower. Now we don't know exactly why. There could be lots of reasons for that. But it was lower, right? The best way I can put it in the estrogen alone arm that showed no difference between breast cancer risk was like here.

    This was the curve, right? The placebo group in the combined estrogen and progestin arm for some reason was really low. They just had a low baseline risk. So then when you looked at the risk of the estrogen and progestin compared to that placebo, it was basically the same as the estrogen alone arms.

    It was the same risk curve. But the placebo group's risk was strangely low. So it made this gap. It looked like there was an increased risk. But the increased risk, many critics who have reviewed the data say the increased risk really seemed driven by the incredibly low baseline risk of the placebo group.

    And so when we look at women who were initiating hormone therapy in the first 10 years, right? Women in this study who previously had used hormone therapy as well, these women did not show an increased risk of breast cancer.

    Sharon Kedar CFA: Dr. Menn, you are a gift to all of us to be tackling such an important topic for women and their families.

    When it comes to breast cancer and hormones, who can't take HRT? And feel free to put vaginal estrogen aside.

    Dr. Corinne Menn: So the way I like to talk about hormone therapy for breast cancer survivors is this. Listen, vaginal hormones are safe and effective to treat your GSM. Genitourinary Syndrome of Menopause I don't care what your breast cancer diagnosis is. You deserve to have a consideration to get a prescription for local, safe vaginal hormones.

    Even if you're on an aromatase inhibitor or Tamoxifen, you can use it. Women who are on aromatase inhibitors, we've got lots of formulations. FDA-approved formulations of estrogen, as well as DHEA in the brand Intrarosa. That could be really safe and effective for you, so talk to your doctor. Great. When we're talking about menopausal symptoms in general, for women who are living with a breast cancer diagnosis, whether an early diagnosis or in the past, the guiding principle is yes, we are going to first lean on to non-hormonal options as the first line for hot flashes and night sweats, and we are going to lean into the five pillars of lifestyle, medicine, nutrition, exercise, sleep, community, mental health. These things are incredibly important because what women who have breast cancer and other cancers, but breast cancer in particular here in the HRT conversation is, if I don't take HRT, I'm gonna get dementia, or I'm gonna get heart disease, or I'm doomed.

    The reality is, even women who are taking HRT, if you don't eat well and you don't exercise and you have a horrifically stressful life and you are not managing those things, the HRT is gonna do minimal in terms of protecting your heart and your brain and all the good stuff, right? So pillars of lifestyle medicine are key.

    And guess what? If you're a breast cancer survivor, you have an extra reason to double down on those and you can live a long, healthy life. But you should understand that breast cancer is not one disease. Meaning breast cancer is heterogeneous, meaning we cannot give blanket recommendations to someone who say, had DCIS, and maybe had a bilateral mastectomy or DCIS and was treated with a lumpectomy and radiation and is doing well. We can't lump her into the same woman who had early stage triple negative breast cancer. She was cured of it. She's done well; she might have even gone many years with a menstrual period after her triple negative breast cancer 'cause there's no hormone suppression in the treatment.

    And maybe now she's going through natural menopause. Or maybe now she's having her ovaries removed because she maybe has the BRCA gene and now suddenly she's plunged into menopause and no one will talk to her about hormones, even though she was allowed to have her natural hormones for years while she ovulated after her triple negative breast cancer.

    We need to have a nuanced conversation for these women and then our estrogen receptor positive breast cancer patients. We need to look at them with nuance and with empathy because it's tricky and we do not have perfect data. Dr. Avrum Bluming and Dr. Carol Tavris do an excellent job in Estrogen Matters at looking at the data that we have. And they admit the data is not perfect.

    No one is saying that all breast cancer patients should be offered HRT. Absolutely not. But what we're saying is, we are grown women who can look at our baseline risk of ever having a recurrence. We can look at what has worked for us in terms of menopausal symptom relief. We can try the non-hormonal, we could do the lifestyle, but if we, as a grown adult woman say, I understand, here's my risk. And there is a theoretical risk if you have estrogen receptor positive breast cancer, that it could come back at five years, at 10 years, at 15 or 20. It's true, ER positive breast cancer can come back at later times in your life. The lower your risk of recurrence at baseline, that's a good thing.

    And so if you're an early stage ER positive breast cancer patient who's completed her treatment, and you're suffering and you're worried about osteoporosis and you've done these things and you want the option of an intelligent conversation of what the data shows, you deserve to have that conversation with informed consent and leaning into all the tools.

    But there is a percentage of breast cancer survivors, probably about 15% who are using hormone therapy. We cannot ignore these women.

    We must treat their menopause, and in certain cases we must give them choice. Because you know what? They gave me a choice to pause my Tamoxifen to get pregnant. They gave me the choice to use IVF medications to preserve my fertility prior to chemotherapy. We have randomized controlled studies that were published in New England Journal of Medicine called the POSITIVE Trial, which supported women with stage one and even stage two disease to stop aromatase inhibitors for up to two years to get pregnant. We give women choice. We studied it. We said, this is an important part of your life to have a baby. We value this, right? But somehow, when we're years past our diagnosis and we might be suffering and we want something for quality of life, or we're concerned, we want to explore this, suddenly the choice is completely off the table.

    Sharon Kedar CFA: It's about the dignity of the conversation.

    I thank you Dr. Menn. You are on the forefront of this and I had chills when you were talking about your own story and I know that we will learn, the world will learn from your story and it is just incredible for you to share your time today and just share what you do with the world. So thank you.

    Dr. Corinne Menn: Thank you for giving me the opportunity.

Additional Resources

Breast Cancer Risk Models & Screening Tools:

Hormone Therapy, Menopause Guidelines & Professional Societies:

WHI & FDA Background Materials:

Publications & Books Referenced

FDA-Approved Therapies Mentioned:

Micronized Progesterone (Prometrium) - https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/20846_prometrium_lbl.pdfings

About Your Host

Sharon Kedar, CFA, is Co-Founder of Northpond Ventures. Northpond is a multi-billion-dollar science-driven venture capital firm with a portfolio of 60+ companies, along with key academic partnerships at Harvard’s Wyss Institute, MIT’s School of Engineering, and Stanford School of Medicine. Prior to Northpond, Sharon spent 15 years at Sands Capital, where she became their first Chief Financial Officer. Assets under management grew from $1.5 billion to $50 billion over her tenure, achieving more than 30x growth. Sharon is the co-author of two personal finance books for women. Sharon has an MBA from Harvard Business School, a B.A. in Economics from Rice University, and is a CFA charterholder. She lives in the Washington, DC area with her husband, Greg, and their three kids.

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Sharon Kedar
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Special episode with Dr. Kelly Casperson on HRT