Pregnancy After Breast Cancer: Is It Safe?

Welcome to The Breastcancer.org Podcast, the podcast that brings you the latest information on breast cancer research, treatments, side effects, and survivorship issues through expert interviews, as well as personal stories from people affected by breast cancer. Here’s your host, Breastcancer.org Senior Editor Jamie DePolo.

Jamie DePolo: Hello. Thanks for listening. My guest is Dr. Ann Partridge, professor of medicine at Harvard Medical School, who holds the Eric P Winer, MD, Chair in Breast Cancer Research at the Dana-Farber Cancer Institute, where she also serves as vice chair of medical oncology. She is also the founder and director of the Program for Young Adults with Breast Cancer and director of the Adult Survivorship Program.

At the European Society for Medical Oncology 2023 Congress, Dr. Partridge chaired a session titled, Pregnancy After Breast Cancer: Is It Safe? She joins us to discuss this session and the factors young women need to take into account if they’re considering becoming pregnant after a breast cancer diagnosis. Dr. Partridge, welcome to the podcast.

Dr. Ann Partridge: Thanks for having me, Jamie.

Jamie DePolo: So, the session at ESMO was labeled a controversy session. So, I have to ask you, how controversial is having a child after breast cancer? Because I know in the session you discussed some of the research that showed that it was pretty safe. So, how, you know, was that to draw people in, or is it truly controversial?

Dr. Ann Partridge: So, it really is controversial, and it’s controversial because, I think with good intentions, there has been a concern for many, many years, probably ever since there’s been breast cancer occurring in women who could still get pregnant, that having a child after breast cancer could throw gasoline on the embers for women who are at risk for recurrent breast cancer, particularly hormone-sensitive breast cancer, and, and that’s not without concern.

Most of our treatments for breast cancer are about reducing estrogen when we’re treating ER-positive breast cancer, and a pregnancy, of course, builds up lots of hormones, estrogen, other hormones related to pregnancy, and so, it’s a reasonable thing to worry that having a baby after breast cancer might have a negative impact on a woman’s prognosis, on her risk of recurrence, if she’s treated for early-stage hormone-sensitive breast cancer so, it’s actually highly controversial. 

And the good news is, we have a ton of data retrospectively that has suggested safety, but people still feel uncomfortable because they worry that the data are biased. And there’s lots of reasons for that, and that’s the reason we did the POSITIVE trial, to do a prospective study to try to remove some of the biases, and that’s why it’s controversial because these are new data and we’re trying to incorporate these new data, and of course, all data are imperfect and have limitations, and that’s really what it was about.

Jamie DePolo: Okay. Okay. Now, I know several times in the session the research of Dr. Matteo Lambertini was mentioned and I’ve done podcasts with him, talked to him. He’s done a lot of research on pregnancy after breast cancer, and I believe, if I’m remembering correctly, that while women who are of child-bearing age who have been diagnosed with breast cancer, they’re less likely to get pregnant than the average woman, most of them do have healthy babies and the pregnancy had no real effect on long-term outcomes.

And so, is it again, because that’s retrospective, looking-back data, rather than prospective data where people are randomized? Which, I don’t know if you could ever do a study like that saying, you know, this group, you have a child, no, this group, you don’t have a child. Was that part of the reason that, you know, those studies are, that there’s still controversy even after those studies, as well?

Dr. Ann Partridge: That’s correct. So, I’ve worked very closely with Matteo over the years. He’s fantastic and he’s done a ton to further the research here, and also wave the flag to highlight this important issue because I think young patients represent only a minority of our patients, but this is such an important issue. And yes, indeed, Matteo’s work has pulled together a bunch of other studies, essentially. He’s done what’s called meta-analyses, which pull together data from other studies, and he created a cohort, particularly of mutation carriers, people with a BRCA1 or BRCA2 mutation, and he looked at the safety of pregnancy in those patients.

Full disclosure, I’m part of his research team when it comes to that. We actually contribute our data from our young women’s cohort at Dana-Farber. But that being said, all of the data that he’s amassed and the meta-analysis that he’s conducted, suffer from the same thing as each of the individual trials, which historically have been retrospective, or registries that were not collected necessarily to look at this question.

And so, that’s what’s so unique about POSITIVE is it’s prospectively-collected data to look at this question. If you went on POSITIVE, you had to have ER-positive breast cancer, you had to be willing to take a break from the endocrine therapy at a particular timeframe, and you had to want to get pregnant, right? And you had to have no evidence of recurrence at that time. And in all of our retrospective data, it’s hard to tease that out. But in this study, you know, which we enrolled 500 some patient worldwide, that was a requirement for getting on the study.

So, it’s a pure, not randomized, so there’s still some limitations because you can’t randomize baby or no baby for women who…what woman would go on that study?

Jamie DePolo: Right.

Dr. Ann Partridge: And so, we couldn’t randomize, but at least we could kind of distill down and make more homogenous the patient population so, we at least knew their intent, and then we’re following them very closely, and also what’s happening to them prospectively.

Jamie DePolo: And you presented those results for the POSITIVE trial at San Antonio last year and they were, to quote the study, positive. I mean, it looked like…I mean, there were some people that had a recurrence, but overall it looked like women who had a baby, it didn’t really affect the recurrence and the babies were healthy. Am I remembering all that right?

Dr. Ann Partridge: You got it right. And so, what we showed was that unfortunately pregnancy isn’t a treatment for breast cancer, and there were women who recurred on the POSITIVE trial, but the recurrences were not more than we would expect from a group of women with similar characteristics in terms of their risk of recurrence. Node positivity, grade, size of tumors, what they were treated with. 

And so, it was very clear from our data that it wasn’t throwing gasoline on some, you know, simmering tinder box and that there wasn’t an explosion of recurrence in this prospective trial so, it validated what we’d seen in the retrospective work, in the look-back work which had more limitations. 

And so, that’s really, really good news, and I think the controversies therefore that we needed to discuss were okay, we now found that in this group of patients there’s no clear sign of harm, but can we translate these data to women with say, stage III disease because the bulk of the patients had stage I or II disease. And are the data good enough because we reported on 41-month follow-up. That’s a little over three years, is that good enough to say, “Oh, it’s perfectly safe,” when you’re talking about estrogen receptor-positive breast cancer where the risks of recurrence go out now unfortunately, you know, 10, 20 years. 

So, that’s what the controversy is now. It’s not that these data aren’t good, they’re very robust. I think everybody agrees, the pros and the cons all agree that they look pretty good, right? And that we, you know, it was a well-conducted trial. Now it’s how do we take those data and interpret them for our patients in the clinic, off-trial, and how comfortable are people saying, fly, be free, have your babies when you want to, whoever you are coming in with ER-positive early-stage breast cancer?

That’s where the debate lies, and some of that’s about kind of comfort with, you know, new data, and some of that’s about, in my mind, talking with the patients, removing our own paternalism and saying to a patient, you know, how comfortable are you with three-year follow-up data recognizing that we’re going to follow these people out, and we could find out that there is some, you know, difference five years from now, and we’ll follow them, recognizing that the retrospective data don’t suggest that. 

Jamie DePolo: Right. Is there any thought going forward with sort of, I don’t know if expanding is the right word, but like, adding women who have been diagnosed with stage III disease to something like the POSITIVE trial or doing another trial that would include them?

Dr. Ann Partridge: Well, we did include them. 

Jamie DePolo: Oh, you did. 

Dr. Ann Partridge: So, they were included, it’s just that they weren’t well represented. So, we allowed anyone with, you know, early-stage breast cancer, and there were 6% of women, or 36 women, who had stage III disease. And you know, when we looked at who recurred on POSITIVE, the higher the risk disease, the more likely a person was to recur, but the vast majority of women, whatever stage they were, did not recur.

And then the other important thing is that when we talk about recurrences, all recurrences aren’t created equal, right? So, a recurrence distant from the breast, chest wall, underarm, is obviously the most life threatening and the one that at least in 2023 we can’t cure. And about half of the recurrences, or the breast cancer events in POSITIVE were distant and that was translated to about 4.5% of the whole population.

So, the vast majority of people didn’t have one of those events, right? 95+ percent didn’t, but among those who did, the 4.5%, those are the ones where we say, “Oh, did the pregnancy change that?” And the answer is probably not when you compare them to the well-calculated control group that we compared them to from recent trials, the SOFT and the TEXT trials.

So, I think we can feel really good at least about the early follow up, and then when you translate for your patients in clinic, I usually say, you know, it’s early data, our retrospective data say it’s safe, these early data could also say it’s safe enough, but in a person who has, you know, 20 lymph nodes positive, I’m worried about them, and even if the pregnancy doesn’t change their risk, that person’s living with a fair bit of risk so, that’s a kind of…very much a conversation with the oncologist and her family and their comfort level with getting pregnant when a recurrence could happen during a pregnancy, during a washout, or during early motherdom if they’re lucky enough to get pregnant and have a baby.

Jamie DePolo: Okay. Thank you. And I know, too, since, you know, the POSITIVE study was done, obviously the people in that study had hormone receptor-positive disease, but we have all these different treatments now. We have CDK4/6 inhibitors, you know, we have anti-HER2 medicines. Do those types of treatments affect the safety of pregnancy or are studies going to look at that? Because if I’m remembering right, I don’t think those were included in a lot of these studies. 

Dr. Ann Partridge: So, that’s a really great point. So, on POSITIVE you could have gotten anything in the way of treatment…

Jamie DePolo: Okay.

Dr. Ann Partridge: …you just had to have gotten at least 18 months of endocrine therapy. 

Jamie DePolo: Okay.

Dr. Ann Partridge: So, some people on POSITIVE probably got CDK4/6 inhibitors on the monarchE trial, right? They could have gotten them. That being said, probably small amount, right? Because it’s not a standard and the studies were limited. And so, I think you make a really good point, and I think if anything, the ones that make it to prime time, as in become approved, those patients are going to be doing better and better, right? They’re going to have lower and lower risk of recurrence, thank goodness for these novel therapies that are changing the, you know, prognosis for women with higher risk early breast cancer, hormone receptor-positive.

On the flip side, and this is true also for the hormone receptor-negative, you know, patients with that kind of disease, the big issue we worry about is the feasibility of pregnancy and the washout period. So, for example, if you take two years of abemaciclib, which is our current new standard for high-risk hormone-sensitive breast cancer patients, they take it for two years. When’s it totally out of their system? When is the damage done out of their system? And then importantly, how much might that impact their ovarian function and their ability to get pregnant? 

We don’t have any good data on that. Same thing with the PARP inhibitors, which we take for a year. Patients take for a year if they have a BRCA1 or BRCA2 mutation and enough risk. And then finally, same thing with like, checkpoint inhibitors, that is like, pembrolizumab or some of the other ones that are being tested right now in clinical trials. But pembrolizumab has been approved in this setting for triple negative breast cancer, pre-operatively and post-operatively. 

And so, that’s where we say we have no good data about how that impacts on future fertility, as well as how it might impact on the pregnancy itself safety, the progeny, the child. We hope once it gets out of the system that the ovaries are good enough, but we don’t know and we don’t know whether those women should be, you know, more likely to be infertile. We know chemo can hurt the eggs, we know that endocrine therapy hurts with time, just the time that it takes, we don’t think it directly hurts the eggs, right? It’s not gonadotoxic for women.

But we don’t know what PARP inhibitors do, we don’t know what checkpoint inhibitors do, and we don’t know what the CDK4/6 inhibitors do like, abemaciclib. So, we need to do more research around that. Really important.

Jamie DePolo: Okay, thank you. And then I guess, finally, so, as you said, this is a very personal, emotional conversation between a young woman and her oncologist and you know, perhaps the spouse. If someone, if it’s one of your patients, a young woman been diagnosed and does want to have a child after breast cancer, what are some of the top things that you sit down and talk to her about? Like, what does she need to consider? I’m, I’m assuming that her own personal risk of recurrence is up there, but what are, what are some of the other things you would talk about?

Dr. Ann Partridge: Yeah. So, first I start with their personal risk. You know, what is their risk of their recurrence as best we can tell? And that has to do with their stage of tumor, the extent of disease, stage, as well as the personality or phenotype of the tumor, you know, the receptor status, the grade, any other features. Was it inflammatory breast cancer? And then it’s, what treatment did you get for risk reduction, and how did your cancer respond if you got neoadjuvant therapy? We know that people have a, you know, pCR [pathologic complete response], which is cancer went away completely with neoadjuvant therapy those people have a much better prognosis than if it didn’t. 

And so, you take all that stuff into account to try and help a person understand well, okay, what’s her risk trajectory over the next five to 10 years, and then how do you feel about having a baby in terms of timing for that person, both in terms of their life, you know, because some people are 25, they’re finishing school, they’re unpartnered, or is this a 35-year-old who was in the obstetrics office trying to get pregnant or they, you know, the IVF doctor’s office trying to get pregnant? So, very different parts of their lives they may be in. So, there’s the social aspects for the woman, and the biologic aspect for the woman or if her, you know, reproductive clock is ticking. That’s obviously an age thing. 

And so, I take their personal preference as well as their disease risk into account to try and help them come up with the best plan for them. One of the things I tell my oncology colleagues that I personally have to do is to say, you know, all risks are not created equal, and people have very different perceptions of risk and what’s important to them. And then also what’s of value for them. 

So, I’ve had patients come in to me and say, “Oh, yeah, the oncologist said to me, ‘You already have one kid, you should be happy.’” And I always joke and say, “I’m a second child, I resent that.”

Jamie DePolo: Right. That’s…

Dr. Ann Partridge: And to tell a woman like, you should be happy with one, it’s really not okay, right? Like, that woman may get there but for a person to tell someone that…

Jamie DePolo: Yeah.

Dr. Ann Partridge: …in that, you know, I think it’s okay to say, “I don’t think you should have a baby because I’m really worried about your cancer…”

Jamie DePolo: Right.

Dr. Ann Partridge: …and this is why. I think that’s okay, but to, you know, that one is good enough is in the eye of the beholder and that we as oncologists shouldn’t be making that decision or that judgement for a patient. And so, be careful. I’ve seen many second opinions and I tell my colleagues, just don’t say anything like that. Please, because people get pissed and they should, right? Wouldn’t you?

Jamie DePolo: Oh, yeah. That’s… I mean, you talked about paternalism at the beginning. That to me seems like the very definition of it.

Dr. Ann Partridge: It’s well, it’s well intended but it just comes out poorly, and I think it…it, you know, all of this is again, well intended but we really…I try to do a pretty explicit values kind of elicitation with a woman and say, well, how important is pregnancy to you? How important…I had someone like this yesterday where I, I said to her, if it’s tricky because her mother was there, too, and I could sense this vibe from the beginning. The patient said I don’t care about fertility, but she’s very young, and her mother cared, and you see this in kind of young adults. The kids, the young adults, they don’t care sometimes, especially teenagers, right? They’re trying not to get pregnant, but their parents are like, yeah, you might change your mind. 

And so, you know, walking that line as a doctor is a whole different thing. But the point is that you want to figure out what’s right for the patient, both in terms of the treatment of the disease, share that with them, and then understand with them where their values lie, because some people care a lot and won’t, will give up therapies. They’ll give up risk reduction because having a baby after or during or skipping something is more important than risk reduction for them. 

And on the flip side, some women look at you and go, I don’t want to do any of that, I don’t really care, and you just want to make sure that they’re aware that they can, you know, and share things like POSITIVE. So, some patients are so scared and they have a low-risk ER-positive breast cancer and I say, you don’t have to be that scared, you know? Let’s talk about this because I don’t want you to close that door because of fears that are not informed by data. 

Jamie DePolo: Right. Right.

Dr. Ann Partridge: You close that door because you don’t want babies. I’m not going to tell you not to have a baby, but don’t do it because you’re afraid of the breast cancer based on what, you know, in a low-risk situation.

Jamie DePolo: Right. Well, I know, and kind of on the flip side, you, you talked about this with the POSITIVE trial results, that there were some women who were not going to take anti-estrogen therapy because they wanted to have a baby. So, they were just going to forego that completely so, you know, obviously that information that you provided was very helpful. 

But you know, I kind of want to ask you one more question about the whole, you know, talking to a younger woman and you talk about closing a door or keeping the door open, and I know obviously you can’t do this, you’re not a mind reader, but that’s got to be very difficult because if it is somebody who’s very young like, say, between 22 and 25, they, their values could change by the time they turn 30 and you know, do you have to talk to them about that? Like, you know, you’re going, you’re making this decision now but remember, you may change your mind in 10 years. Is that something that you have…I mean, it sounds like you have to be a psychologist and an oncologist.

Dr. Ann Partridge: You’re 100% right, and I have three young adult daughters which I’ve learned a lot from, and I also have learned a lot from my patients over the years before they became young adult daughters and so, I think I’m pretty careful and thoughtful and I would implore all of my colleagues to be this way. And I think, I do try and tease out where they are today and try and make sure that they know their options and that people do change their mind about these things over time.

And most young women, even in their early 20s or younger, they get it. You know, they, they might be mad at their mother and the mother’s pushing an agenda or something, or their parents, I don’t need to single out the moms, but most of them are, you know…or they just say no, I don’t care, and then I say, okay.

The good news is that our modern-day breast cancer therapies, at least the ones we know about seem to be the least toxic on the youngest ovaries and so, they kind of get a pass anyway from the majority. Not everything and you know, not with all diseases, but when we’re talking about our common breast cancer regimens, the younger you are the less likely it is to make you infertile, and so, that’s a, that’s a good thing. They can kind of grow out of it if they’re really not in a place to think about this stuff yet.

Jamie DePolo: Okay. Dr. Partridge, thank you so much, this has been really helpful. I know it’s going to help a lot of people and I really appreciate your insights here.

Dr. Ann Partridge: Thank you, Jamie.

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