B (7:13)

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C (7:59)

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B (8:33)

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A (8:41)

All right, fascinating stuff. And this is why our tagline is medicine moves fast. Because, man, it's moving fast on this topic. First, I think we need to do quick reminders of stuff that we forget. It's kind of in the back of the hippocampus. Got to drive that up to the frontal lobes. So first, let's talk about numbers. All right, this is important just to get an idea of population at a glance so we know what we're talking about here. First, According to the CDC and the National Comprehensive Cancer Network, about 5 to 10% of all breast cancers are hereditary. And among those, BRCA 1 and 2 are responsible for about 60% of the cases. Okay, so we're not talking about the general population, but we're just looking at breast cancers themselves when they've already been diagnosed. 5 to 10% are some form of hereditary mutation. BRCA 1 and 2 are 60%. Remember, there's others that don't get a lot of attention, and that's because BRCA 1 and 2 are about 60%. More than half. So the majority are those, but there are others. Okay? Now, at a population level, however, only about 1 to 2% of all breast cancers in the general population are caused by BRCA mutations. All right, so you see the difference. Looking at Everybody, it's only 1 to 2%. But when you look at those who are diagnosed with breast cancer, that's 5 to set 5 to 10% of all breast cancers. All right? So know that the numbers, because they're a little bit different based on which population you're looking at. Now, as I've said many times before, I love our podcast community because this comes directly from that Question super, super deep. Shouldn't they take out the uterus at the same time that this podcast family member's family member is having risk reducing a BSO for her BRCA status? Fascinating. So I'm going to tell you with a little bit more verbosity what I answered back because it's very timely because of this recent data from 2025. Okay, so again, back to our basic stats, back to our basic science component, if you will. BRCA1 sits on chromosome 17, BRCA2 sits on chromosome 13. BRCA1, 17, BRCA2, 13. Both are tumor suppressor genes, when they take a hit, causes cells to go haywire because now the tumor supp suppressor is now not functioning correctly. All right, so BRCA 1, 17, BRCA 2, 13. Now here's what the numbers look like for a carrier women who have a pathogenic BRCA1 mutation. Let's do BRCA1 first. Have a lifetime risk of breast cancer of about 57 to 72%. I would remember like 50 to 70. Okay, 50 to 70. Now that's gonna make sense because the risk of ovarian cancer just abuts that going down. It's about 40 to 50%. Okay, so that's how I remember BRCA1. Breast cancer is 50 to 70. And then what started at the 50? Just take that down to about 30. So 30 to 50 is ovarian cancer. The lifetime risk for breast and ovarian cancer with BRCA2 is still high, but it's a little bit lower than it is for BRCA1. So that breast cancer is around 40 to 60 for breast cancer, and then ovarian cancer is around 11 to 20%. Okay, so you don't want either of them. But BRCA2 has lower overall risk prevalence than BRCA1. Now, the traditional recommendation, as we said in the intro from the National Comprehensive Cancer Network and international societies, was that in order to reduce the risk of a cancer that we don't have good screening tests for ovarian, tubal, peritoneal, you got to get those suckers out when fertility is done. But the age at when to do that varies based on BRCA status. Okay, so very quickly, let's do this quick. For BRCA1, the rate, the best time to undergo risk reducing BSO is around 35 or 40. So remember BRCA1 because it's higher incidence, you got to get out earlier. So 35 to 40, and then it's between 40 and 45 for BRCA2. Again, you can have a little bit more leniency if you will, for BRCA2. I always remember though, 40, because 40 is the watershed. Age 35 to 40 with BRCA1 and then age 40 to 45 with BRCA2. I just remember 40 and I split the difference. Okay, so is there a role for removing the uterus at the time of risk reducing bilateral subpingual oophorectomy? Now, again, historically, uterus was just kind of left in place and all it would do, of course, is run the potential for a continued cervical surveillance, cervical cancer, endometrial cancer, even though BRCA doesn't raise that risk. Well, let me back up. There was one weird meta analysis that said maybe like papillary serous endometrial cancer, which is very rare, could be increased in BRCA patients for the uterus. But that really hasn't borne out in other population studies. The point is, if the uterus is just sitting there and its job is basically not there anymore, shouldn't we just take it out? And that opens up the avenue for estrogen only therapy as opposed to estrogen and progestin therapy? Not. Let me say that right now, guys. Not that estrogen and progestin therapy is harmful in these patients. It is not. But it's not the same goodness as estrogen only therapy. I'm gonna explain that in just a minute. Okay, so let's get into this now because I want this to be relatively quick because it's fascinating and I just want to focus on two main publications, both from 2025. The latest one from August 2025, which was by a physician I respect very much from University of Florida, Jacksonville, that is Andrew Konitz, a phenomenal, phenomenal leader and researcher. Just wonderful. Been around forever. And I mean that in a good way. But Andrew Konitz et al. Helped write a commentary, a narrative review actually, on menopausal therapy after risk reducing BSO in BRCA carriers in The Green Journal, August 2025. And we need to cover this. Okay? So first of all, before we get Into Andrew Conit, Dr. Conit's narrative review from the Journal of the national cancer institute in 2025, we have to talk about the Katsopolis publication. That's with a K. Katsopolis. Okay? Now this was a prospective study. This was prospective data from BRCA1 carriers that showed. Here it is, guys, let me just hit you with it quickly. That estrogen alone, hormone therapy after olfactomy was associated with. Here it is. A statistically significant decreased risk of breast cancer compared to no HRT use at all. Now let's Stop there for a minute. So remember, these are BRCA patients who had risk reducing olpherectomy and then were given estrogen only therapy. Their risk of breast cancer was less. The hazard ratio was 0.37. So everybody freaks out. Hey, you're giving a BRCA patient estrogen replacement therapy. Of course, because there's never been any data that's been harmful, but now we have data that's actually protective. It actually reduced the risk with a hazard ratio of 0.37 with 95% confidence intervals that were under 1. It was 0.2 to 0.5. It worked. Okay, how weird is that? Now, here's the catch. Estrogen progestin therapy thankfully didn't show an increase. It just didn't show any protective effect. It actually had no effect at all with a hazard ratio that was pretty darn close to 1 at 0.94. Do you all see this? So put this in perspective. Just last year, Journal of the National Cancer Institute, hey, BRCA patients who get estrogen only therapy actually had a hazard ratio of 0.37 with a confidence interval under one that was protective against breast cancer. What? Mind blowing. So let's say that again. Estrogen therapy decreased the risk of breast cancer in BRCA carriers. Fascinating. Fascinating, fascinating. But there's a catch. There's a catch. So don't lose this, okay? Because, yes, that statement is true, but the protective effect was particularly pronounced. Okay? So it was mainly seen once you do the scatter graph. It was mainly seen in women who underwent olpherectomy before the age of 45. So there seems to be an age dependent risk factor here. And this goes all the way back to these same authors who published in JAMA Oncology in 2018, that when you have prophylactic olpherectomy under the age of 45 and start estrogen therapy, it can be helpful. Even if you start estrogen progestin therapy, it can be helpful, but the catch is that you'd have to have olpherectomy at or under the age of 45. Over age 45, there was potentially the increased risk with hormone therapy. Okay, so you see, there's two things here, guys. The age that went to surgery was done. That's why I said just a little while ago, I always remember the age of 40, because as long as she's done with fertility, BRCA1 or BRCA2, I recommend you get out at 40, because then you can start estrogen only therapy, especially if you have a hysterectomy, which is really what should be done. Or even if you start estrogen and progestin therapy, it doesn't reduce the risk of breast cancer, but it doesn't necessarily increase it either. However, you want to do that under 45, because there is some evidence that the risk may actually increase a little bit with estrogen and progestin therapy at or over the age of 45. So two things. The age of when you had it done, and then the type of hormone therapy that you received with a protective effect being noted with estrogen alone. Now, remember, guys, this isn't just about hot flashes, even though that's a big thing, because unlike natural menopause, remember that surgical castration, which is what we're doing here, removing the tubes and the ovaries, you know, there's a precipitous drop in ovarian function because they're out of the body. Much more aggressive hot flashes, much more mood issues, much more sexual dysfunction because there's no normal climacteric transition. There's no perimenopausal interval where the body kind of adjusts. All right, so there's like ovaries in, next morning, ovaries out. So these patients need some kind of hormone therapy. And I want to be very clear. Even estrogen progesterone therapy in these patients has not been shown to cause breast cancer. I'm going to give you that data in a minute. But the unexpected perk is that if you could just give them estrogen by themselves that actually seemed to be protective of breast cancer. Now, what I mean by themselves, I mean systemically, we'll get into. Maybe the effect is there with a progesterone releasing IUs. I get that. However, there's still some progesterone that enters the system. So it's not a clean study. All right, we're talking about uterus out, since its job is not there anyway. Not there anymore. Anyway, just remove it. If the patient desires a shared decision making so that you can just do estrogen only therapy and it's one less thing to worry about. Okay? Now if you think this is like just my opinion, it is not. I'm going to give you the direct verbiage here in just a minute, all right? Because the quote from this author is striking. But I have to. Let's pause the breaks here. Put. Pump the brakes here for a minute because I don't want. Even though I've reset it, I have to say it again. I don't want to give the. The idea that combination hormone therapy in these patients is somehow bad that is not what I'm saying at all. This was actually Andrew Conditz's point in that narrative review from August 2025 in the Green Journal where he states, quote, prospective studies of patients with BRCA1 or BRCA2 did not demonstrate an increased risk of breast cancer with menopausal hormone therapy. They go on to say, quote, similarly, in matched case control studies, the median duration of menopausal hormone therapy use of four to five years was also not associated with breast cancer risk. End quote. So I'm not trying to throw estrogen and progestin therapy under the bus at all. These patients need hormone therapy even after risk reducing septing olpherectomy because they're at dramatic risk for quality of life issues. Estrogen replacement therapy, either alone or with progestin is safe. What the data is showing though, is that if you can just give estrogen by itself, it seems to not only be safe, but seems to be protective of breast cancer. Do you all get this now? They're not going to take it for life. They're supposed to take it until the age of natural menopause and then taper down. Even though the Menopause Society, formerly called nams, North American Menopause Society, says they can take it for as long as they want to without stopping at a set age, as long as they understand risks and benefits. But for me, because there are BRCA patients, I would probably stop that between the age of 50 and 55 with a taper down effect and then switch to a non hormonal agent like maybe Vioza. She's almost left my, my. Almost with my brain there, which is Venalizident or Linkette, which we've talked about as well. The two neurokinin B antagonists. Right, the non hormonal agents that work centrally on the brain. We've covered both of those. Vioza or Linkette. Okay, so what was I doing now? I have totally left. I have an outline and none of that has been. I haven't even looked at that. Did I talk about the quote from Candidates? Yes, I did. All right, so Candidates gave that data that even estrogen and progestin therapy is okay in these patients. It's okay, y'. All. Even birth control pills? Birth control pills are all right because the amount of estrogen in the body after conversion of ethyl estradiol is nowhere close to the estrogen that is reached at mid cycle during ovulation. So yes, you can give low dose birth control pills in a continuous fashion. That's preferred Rather than cyclic, just keep it at a constant dose that is not harmful for BRCA patients. And I have an episode on that several years back called like OCPS and brca. Yes. Or something like that. So yes, these patients can take birth control pills. These patients should not be discouraged from pregnancy. Nothing wrong with that because they're a reproductive age. But they should kind of get the show on the road here so they can try to finish up by age 35 at the earliest or 40 based on their BRCA status. Okay.

C (23:39)

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A (24:10)

Where am I going to now? All right, now that I've said all that very quickly, let me give you the quote from the study from 2025 from the Journal of the National Cancer Institute. If you all can't tell when I get all fired up, I like, I don't even look at. I'm supposed to look at the script. I'm getting little messages like you're all over the place. Yeah, thank. Because this is so exciting. Honestly, I find this remarkable. And what a good question from our podcast family member. But let me read you this quote from the publication from the Journal of National Cancer Institute. Also just from last year, 2025, which was the Katsopolis publication. This is a bold move. So if you all want to send me a message that I oh my gosh, Chava wants to take away people's uteruses. Uteri. Uteruses. Uteri. At time of surgery. Yeah, I do. If it's for a BRCA patient. Because the ovaries are coming out, the tubes are coming out. May as well get the central part. Why not? Especially because the job of the uterus will no longer be there. Okay, so this is the quote, not mine. This is the quote from the authors from 2025 and back in the JAMA Oncology publication in 2020, 2018 from Katsopolis. Listen to this powerful quote. Women undergoing preventative olfactomy, particularly women undergoing oophorectomy prior to age 45, should consider removal of the uterus to avoid the use of progesterone containing hormone replacement therapy. End quote. Now, to be devil's advocate they are talking about systemic estrogen and progestin. Maybe using a progestin in the uterus is a little bit different, but because there is still some systemic absorption, that would not be a clean estrogen only therapy. Y' all get that right? Because even though the progestin is just hanging out in the uterus, there is still some absorption. And it's unclear how that works with a BRCA patient. But we know, we don't have to guess. We know that estrogen only therapy in BRCA patients who have had their tubes and ovaries removed, estrogen only therapy gave an odds ratio, or a hazard ratio rather of 0.37. Amazing. So can you imagine my met my response to our podcast family member? I tried to put all of that in random text and I voiced to text, so there's typos in there. It was terrible. But I was so excited. I'm like, wow. I mean that's a cutting edge question. Yeah. Now, we're not typically in the business of taking out normal organs, but hello, welcome to the world of gender confirming or rearrangement. However we're calling it now surgery. That's exactly what's done for that, for a gender dysphoric issue. Whereas this has real medical implications with hormone therapy. Do you see how things change based on the flavor and the environment and the culture of surgery? So while uteri were left in place and we just took out the tubes and the ovaries because that's the site of origin of what we're trying to prevent, there is now growing commentary. And again, Andrew Conditz mentioned this in the August 2025 narrative review in the Green Journal as well. Just take out the uterus and give the patient estrogen only therapy, because that has not only quality of life benefits, it has bone benefits, it has metabolic benefits, it has cognitive and mood benefits, sexual benefits. Why not just do it? It never made much sense to me. What is uterus doing there anyway? It's just kind of hanging out there and now we have to add a progestin just to protect it when we're using the very indicated hormone therapy. Fascinating. So we all started this with the question hysterectomy plus BSO for BRCA risk reduction. Yes. Now that's not a formal guidance, but the commentaries, the data happens first and then the ship turns around. So I'm telling you, you remember you heard this here first because we're covering this and the tide is definitely going to move to a shared decision making model of what to do with the uterus for these patients. Podcast family, as always, we're thankful for you. Thank you for your wonderful questions that come in. That was a fascinating, great question. Thank you for asking. And now that we've done all that, Michael, let's take it home. Foreign. This is Dr. Choppas, obgyn clinical pearls no spin podcast.