In the Pursuit of Parenthood: Pregnancy, Breast Cancer, and BRCA Mutations

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals. Exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale. Shepard, a Medical Oncologist here at Cleveland Clinic directing the Taussig Early Cancer Therapeutics Program and co-directing the Cleveland Clinic Sarcoma Program. Today I'm very happy to be joined by Dr. Halle Moore, Director of Breast Medical Oncology at Cleveland Clinic. She's here today to talk to us about the safety of pregnancy after breast cancer with BRCA mutations. So welcome.

Halle Moore, MD: Hi, Dale, nice to see you again.

Dale Shepard, MD, PhD: Welcome back, I guess, we have some previous episodes people can look up.

Halle Moore, MD: Thank you.

Dale Shepard, MD, PhD: So tell us again a little bit about what you do here.

Halle Moore, MD: So as you mentioned, I direct the breast medical oncology program and co-direct our comprehensive breast cancer program for the Cleveland Clinic.

Dale Shepard, MD, PhD: Excellent. So we are going to talk about pregnancy and breast cancer. So I guess this is a very important topic because oftentimes breast cancer occurs in women who might be thinking about pregnancy. There was some data that came out recently at San Antonio Breast Conference, is that correct?

Halle Moore, MD: Yeah, so we participated in a study looking at breast cancer outcomes in young women who carry pathogenic mutations in the BRCA genes, and that was presented at the San Antonio Conference and then actually more recently published in JAMA.

Dale Shepard, MD, PhD: Excellent. So tell us a little bit about what led to the study and what the findings were.

Halle Moore, MD: Yeah, so we have a fair amount of information now with respect to pregnancy safety after a breast cancer diagnosis. We've had a lot of retrospective data suggesting that outcomes in terms of breast cancer are very good. And now we even have a prospective study demonstrating the safety of interrupting endocrine therapy in order to conceive. And again, all the data suggests safety. However, we have very limited information in the subset of young breast cancer survivors who carry these pathogenic mutations in the BRCA genes.

Dale Shepard, MD, PhD: And so when we think about the subsets of patients with breast cancer, what were some of the factors that led us to think that maybe there would be differences?

Halle Moore, MD: This is a group of patients who may have more concerns about pregnancy with respect to am I going to pass on a gene mutation to my offspring? Or perhaps there are fertility concerns, there's some data to suggest that women who carry these mutations may have some fertility problems. And also it's frequently recommended that these women undergo risk-reducing oophorectomy and salpingectomy, and so for those reasons pregnancy may be more challenging. In addition, these are individuals who are predisposed to a higher risk of future cancers, and so all of these may weigh into their concerns about future pregnancy.

Dale Shepard, MD, PhD: And so what does that look like in terms of women that might be thinking about getting surgeries that of course would not enable them to have children timing-wise? I mean, they've been treated for breast cancer, they need maintenance hormonal therapies, for instance, they're thinking about pregnancy, they're thinking about preventive surgeries, how do you walk through what to do and when?

Halle Moore, MD: Right. So these are discussions that are very much individualized depending on the age of the patient, their future reproductive concerns, and perhaps their family history in terms of whether there is a family history of ovarian cancer, what age that occurred at. But interestingly, even women who have undergone risk-reducing surgery for their ovaries can actually still become pregnant now that we're able to support these women hormonally with assisted reproductive technology.

Dale Shepard, MD, PhD: And tell me a little bit about that, when we think about the ability to do hormonal therapies, hold hormonal therapies, do these reproductive technologies.

Halle Moore, MD: So the study that we participated in recently, it was a retrospective study, so it really didn't look at this issue of holding versus not holding endocrine therapy, we do have information on the receptor status of the individual patients and how likely they were to have pregnancy. So for instance, those with ER-negative disease were more likely to achieve pregnancy than those who had ER-positive disease. And the time to pregnancy was longer in patients with endocrine-responsive disease, presumably because they were waiting until some good time on endocrine therapy prior to starting.

In terms of assisted reproductive technology, in our retrospective study most of the women achieved pregnancy spontaneously, so did not require assisted reproduction. So obviously that means that many of them held off on having their ovaries removed until they'd completed childbearing, which is what we often recommend.

We do have an ongoing analysis that is looking at the safety of the assisted reproductive technology in these individuals who carry these mutations. So we will have more information coming out about that in this cohort of patients.

Dale Shepard, MD, PhD: So one of these studies, it showed a pregnancy rate of about 22%, in that ballpark, is that higher or lower than you would've thought?

Halle Moore, MD: I think it's actually a little higher than we might've expected. So we did include only women under the age of 40 who carried BRCA mutations, and we only looked at pregnancies occurring after their breast cancer diagnosis. So we didn't count any pregnancies that happened before they were diagnosed with breast cancer. So one in five patients becoming pregnant in this cohort I thought was quite a lot.

Dale Shepard, MD, PhD: What sort of factors played more of a role in the ability to have a successful pregnancy, hormonal status you mentioned briefly, mutation status, what were the most important factors?

Halle Moore, MD: Yeah, so a major factor is that the younger the patient was the more likely they were to become pregnant. Now, of course, we were not able in this retrospective study to collect information on pregnancy desire in these patients, but certainly younger age was associated with a higher likelihood of achieving pregnancy, as was negative hormone receptors and earlier stage cancers.

Dale Shepard, MD, PhD: Makes sense. I guess when you think about timing, women get a breast cancer diagnosis, they go through treatment, they may want to have children. What's the general guidelines, and of course it's individualized, but I'm guessing there's concern on the part of the patient and you as the provider, what's a safe period of time to make sure this isn't coming back before you start a pregnancy? How long is too long to wait if you're thinking about these surgeries for ovaries and things like that? What's kind of the sweet spot there?

Halle Moore, MD: Yeah. So the conventional wisdom has been to wait two years after a breast cancer diagnosis before attempting conception. That's certainly what was done in the positive study where it required interruption of endocrine therapy. Certainly I've had patients in my practice with ER-negative disease who have chosen to attempt sooner. But of course what we want to avoid is the development of a recurrence while that patient is pregnant. So we just want to make sure that they're doing well before pregnancy is attempted.

We also want to think very early on, before we start any treatment for the breast cancer, about what their goals are with respect to reproduction because there are things we can do in advance of cytotoxic chemotherapy treatments or prolonged endocrine treatments to enhance their prospects for future fertility.

Dale Shepard, MD, PhD: Yeah, which is what came to mind when we talked about the one in five being able to become pregnant, seemingly a lot of these women may have had chemotherapy. Tell us a little bit about that and how we might be able to avoid problems.

Halle Moore, MD: Yeah. So one way to help maintain fertility is being young at the time of diagnosis. And so I think because we looked at a younger subset of patients, that's why we saw a little bit higher pregnancy rate than we might've expected. There are medications we can give to suppress ovarian function during the chemotherapy, and that reduces the risk of early menopause as a consequence of the chemotherapy. And then we also would always offer consultation with a reproductive endocrinologist to look into freezing eggs or embryos prior to any type of chemotherapy.

Dale Shepard, MD, PhD: You mentioned things like the reproductive endocrinologists and things like that, these are no doubt emotionally charged discussions, these are not easy office visits and conversations. Who gets involved? How do we work in a multidisciplinary way? What other resources do we use to help out?

Halle Moore, MD: Yeah. Well, so we really feel that the sooner we can start these discussions the better. So it really depends on your practice. We tend to see at our institution patients in a multidisciplinary manner. So the first day that they're meeting with the surgeon, they're also meeting with the medical oncologist and other providers as well. But in other instances, they may be seeing a surgeon first and not seeing a medical oncologist till after their surgery. So it's important that all of the providers be aware of the resources that are available and make these referrals as early as possible.

We also have social workers in our clinic, psychologists if that's necessary to process some of this information. So it really is a group effort. We also have very good connections with our reproductive endocrinologist to get our patients in quickly so that we can really give them the best chances to do what they need to do without delaying their important cancer treatment.

Dale Shepard, MD, PhD: Makes sense. So looks like there have been some successes, but where are the gaps, what do we need to be thinking about to make things even better for these patients?

Halle Moore, MD: Yeah. So I think there's still a lot of oncologists who warn their patients not to become pregnant or that are very concerned about the safety of pregnancy after what is often a hormone sensitive disease. And so I think getting this kind of information and learning that patients can do very well with pregnancy and the pregnancy outcomes are generally very good for these individuals. But that we often need to do things ahead of time to assure that they have those opportunities.

Dale Shepard, MD, PhD: And I guess it seems like sometimes a younger population, dare I say, more informed for lack of a better way to put, population, so I think fertility preservation thoughts probably a little bit more top of mind in breast cancer than some other diseases. But room for improvement in that area as well?

Halle Moore, MD: Yeah, I mean, so because we have so much data in breast cancer, I think that patients are able to access information on the internet and read about this. And I think there is good knowledge among breast cancer providers for other disease types where a diagnosis in a young female may be less common, it just may not be at top of mind. So I think it is important regardless of the type of cancer an individual has that these issues be addressed for young women.

Dale Shepard, MD, PhD: So, it seems like important issue, if we think about all the breast cancer awareness things going on, this is a really, really important part to make sure people are aware of.

Halle Moore, MD: Yeah, it's the kind of thing that you don't want to put somebody through chemotherapy, remove their ovaries, whether it's for risk reduction because they have a genetic predisposition for ovarian cancer or because they are using that as part of their hormonal treatment for their breast cancer. And then have them realize, "Oh my gosh, you mean I could have still had children if only I'd known that those were options ahead of time." So we don't want to close windows for people.

Dale Shepard, MD, PhD: Yeah. I guess a couple of other things, are there patients, patient characteristics, patients you see that you think it's a bad idea to talk about having children and exposing them to extra risk because of their breast cancer? Who are some of the patients you'd be concerned about? We talked about how we sort of encourage it if people that are interested. Are there people you'd just say bad idea?

Halle Moore, MD: Yeah. So that's a really important question. So this is a time where it's important to have frank discussions with individuals about what their risk is for this cancer recurring or metastasizing. And a patient with a very high risk cancer, perhaps you're not going to alter their risk of the cancer coming back with a pregnancy or no pregnancy. However, they need to be aware that they may not be around to raise that child if they have a very high-risk situation.

We're now actually running into situations where we have patients with metastatic breast cancer who are doing so well, they want to have children. That's a situation where it is rare that we can safely interrupt treatment for a pregnancy. So these can be challenging discussions as people are doing better and better.

Dale Shepard, MD, PhD: Yeah, I guess that's sort of a measure of success, people are living longer, they feel better, and then these sort of issues come about, huh?

Halle Moore, MD: Yeah.

Dale Shepard, MD, PhD: It's unfortunate. Are there other trials that we're working on here at the clinic that might help answer some of these questions, or really education being one of the key components right now?

Halle Moore, MD: Yeah. So we don't have an active trial right now looking at this particular issue. However, we have ongoing collaborations with our colleagues in reproductive endocrinology, and are always ready to look at new questions and try to find more answers.

Dale Shepard, MD, PhD: And I guess you have a really well-developed way to address these questions, so are there people that you may see in clinic, really to have these discussions about resources available, risks and things, you may not have even treated their cancer, but they have these questions, and maybe providers might be listening in might say, "I don't really feel equipped to address that, maybe I needed some help"?

Halle Moore, MD: Yeah, so I think this is a very appropriate reason to get a second opinion, and these can be challenging issues to address. And oftentimes there are solutions that either somebody experienced in this may be able to come up with, or our reproductive endocrinologists may have answers. There are topics that our reproductive endocrinologists can discuss like surrogacy that may apply to some patients who thought they couldn't otherwise have children. So yeah, I think this is something that if one is not comfortable with the discussions, we have plenty of resources that can help.

Dale Shepard, MD, PhD: Excellent. Well, it's a really important area. And you're doing really important work within it. And appreciate your insights.

Halle Moore, MD: All right. Well, thank you very much.

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