From Breast Cancer Patients to Healthy Mothers

TRANSCRIPT:

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Dr. Chuck Ryan: ​This is The Good News About Cancer. I'm Dr. Chuck Ryan.

Dr. Alicia Morgans: And I’m Dr. Alicia Morgans. 

Chuck: We're oncologists, and we've spent our careers working to understand cancer. We believe that there's more progress now in research and treatment than there ever has been, and we're here to share that with you.

Alicia: In each episode of this show, we talk to one of our colleagues about a new development and cancer treatment or diagnosis. We'll break down what's new, why it matters, and how it points the way forward.

Dr. Ann Partridge: What we saw was not only did the pregnancy not increase the likelihood of a recurrence, but actually it was pretty much dramatically the other way. 

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Chuck: So, Alicia, today we're going to talk about pregnancy during treatment for breast cancer, which gets us into an area of oncology where frankly you are one of the world's experts. And that is survivorship. And how to live life during cancer treatment, after cancer treatment. It is really a discipline in and of itself. 

I wonder if you might want to help us introduce this topic, not only of pregnancy in breast cancer treatment, but also just cancer survivorship in general.

Alicia: Sure, and thanks. You know, I think after a diagnosis of cancer, it's really easy to be overwhelmed, and of course when you're going through all of the treatments or living after treatment, and cancer survivorship is really an area of care that tries to help support people through that as whole people. And make sure that they get through on the other side as well as they can, and hopefully in great shape.

So one of the ways that people want to get on with their lives after this diagnosis is to do some family planning, or continue family planning, because cancer interrupts what we want to do. 

So when we think about that in particular with breast cancer, we know that many of these cancers are actually fed by the hormones that are needed for a healthy pregnancy. These hormones, like estrogen or progesterone, are absolutely necessary to have a healthy and normal pregnancy – without them, people can't get pregnant – and they're the exact same hormones that feed some of these cancers. 

So women, after treatment for breast cancer, or if they're on ongoing treatment with hormone-lowering medicines after breast cancer, really have a lot of stress around getting pregnant – and a lot of fear. 

Chuck: So one of the treatments that women take in the course of their treatment for breast cancer is called endocrine therapy. You may have heard of some of these drugs, Tamoxifen, aromatase inhibitors. Many of them are actually even advertised on TV. So they're very commonly used drugs. And most importantly, in this context, is that they're taken for a long time, five or ten years even. And so when a young woman who is of childbearing age has to take one of these therapies, the duration of therapy means that by the time she finishes, she may no longer be of childbearing age.

Alicia: Absolutely. And a lot of people won't even consider getting pregnant after a diagnosis of breast cancer or don't have the opportunity because their doctors tell them that they don't have evidence that it can be safe. But there has been a trial that recently showed us that not only can we have a healthy pregnancy and a safe pregnancy, but also healthy babies on the other side. 

This was a really important study called the POSITIVE Trial, which is a clinical trial that looked into whether people could get pregnant safely after their diagnosis, and during their treatment. And pause their cancer treatment in order to have that pregnancy. 

And one of the lead researchers is a colleague and a friend of mine, Dr. Ann Partridge. Dr. Partridge is the interim chair of the Department of Medical Oncology at Dana-Farber Cancer Institute, where I work, where we both work. And she's a professor of medicine at Harvard Medical School.

Let's hear our conversation with Dr. Ann Partridge.

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Alicia: So Ann, I think one of the things that's so important just to set the stage for people to understand breast cancer– this is a cancer that's really driven in a lot of ways by hormones, by things that our bodies make that can be female hormones, male hormones. 

Can you tell us a little bit about how these hormones, what, what they are, how hormones like estrogen, progesterone might affect a breast cancer, but also how they're really important for pregnancy?

Ann: So hormones are super important for all of us – men and women in our reproductive hormones, estrogen, progesterone, androgens – these are the female and male conventional hormones. And we all have them all, just in different proportions. And in breast cancer, the majority of breast cancers that are diagnosed, whether people are young or older, have estrogen receptors positive and progesterone receptors that are positive. 

And one of the things we've learned for many years is that if you target those receptors with hormonal therapy – drugs that either block the estrogen receptor or lower estrogen in a woman's body – you can actually treat breast cancer. And in early stage breast cancer, that reduces the chances that you would hear from that breast cancer again. So it's been a mainstay of therapy for women with early stage hormone-sensitive breast cancer to get hormonal therapy. 

And so, it's really important that we try and do that. And at the same time, we know in pregnancy there are a lot of hormones flying around at high levels, and those include hormones that are reproductive hormones and including estrogen and progesterone. And so we've always worried that a pregnancy might impact on the risk that a breast cancer might come back, by virtue of affecting or getting in the way of the ability to block a hormone, right. 

And it brings up this clinical conundrum that women want good breast cancer treatment with the hormones for five to ten years, which is the conventional time that we give them. And yet also, if they're diagnosed and haven't completed their families, they may want another pregnancy. So trying to help them to sort that out and do it safely is a big area of research.

Alicia: So I know you were recently involved in a trial that looked at a new strategy to help women with breast cancer become pregnant. I wonder, could you just share in a sentence or two what you looked into and what you found in that really important investigation?

Ann: So the study that we did was to say, we know that hormone-sensitive breast cancer comes back, and the hazards, or the risk of it coming back, in year five or six is not that different from the risk of it coming back in year two or three, or the risk of it coming back in year ten. 

And so the question was: instead of treating with all of our endocrine therapy upfront, which is what we historically do, just like when we do the chemo and the radiation and the surgeries. Could we take an interruption or a break from the endocrine therapy for pregnancy and then get back on, complete the full course and have patients have similar outcomes as if they had done a full course of endocrine therapy? That was the premise of the POSITIVE trial. 

And the good news is that our early findings, looking at it at 41 months median follow up from enrollment, which was about on average two years out from diagnosis, is that it does appear to be safe to take that break and get back on. 

Alicia: So this is all fantastic news, obviously for the moms, but tell me a little bit about the babies. I wanna hear about the babies, Ann! Were they okay? They were normal babies, right?

Ann: Yeah. So, the babies were looking okay, overall, that was the other really good news. So first, the vast majority of women who went on positive got pregnant, the majority of them had a live birth. 

And a nice proportion, somewhere in the 20% range used IVF or reproductive technology strategies to get that pregnancy. And so we allowed people during that break to do what they needed to do to get pregnant. It wasn't the majority, but it was a substantial minority who indeed did use reproductive technologies. And of course that was more likely if women were older, generally. 

Chuck: What was the upper limit of the age group here? Where you say an older patient, how old were some of these women who were able to get pregnant during this pause?

Ann: So the upper limit was 42. And so when we thought about like, what was the older age group? It was the women who were more in their late thirties to early forties.

And that's, you know, kind of, you know, the older people use the reproductive technologies and had success. The younger people got pregnant on their own and sometimes used the reproductive technologies, for different reasons. 

The other thing was to get back on the endocrine therapy. So some people wanted to have very short times off. And other people, you know, took the full two years plus to do it, because we supported and recommended per protocol to try and get off, have a washout so that those babies wouldn't be exposed to endocrine therapy in utero. So they needed to have a washout before they could try to attempt pregnancy. And then up to two years total off the endocrine therapy for, you know, hopefully a pregnancy, nursing, if they were interested in that and it was feasible. And then getting back on the endocrine therapy, that was the goal.

Not everybody got back on the endocrine therapy, nor did everybody get back on it, within the two years. But people were pretty close and the majority got back on it. 

Chuck: So the take home message for future generations of women going through endocrine therapy for breast cancer is: it appears safe, no increased risk of breast cancer recurrence during that pause or even after that pause, to get pregnant. 

Ann: Very much so, and the cool thing is we actually looked and did a landmark analysis among the women who got pregnant on POSITIVE, and we compared them to the women who didn't get pregnant on POSITIVE. And all of them had to be disease free at 18 months. And what we saw was not only did the pregnancy not increase the likelihood of a recurrence, but actually it was pretty much dramatically the other way. 

So the women who had gotten pregnant had way fewer events than the women who didn't in that landmark analysis, which really, I think, nails the coffin on the idea that a pregnancy causes a recurrence. Which is very exciting. That's the first– we've seen that in other data, but everybody called it the healthy mother bias, and you can't, you know, maybe a recurrence was brewing, but in this setting, prospectively, we showed that. So we can feel pretty confident about that. We'll see what five-year follow up shows.

Chuck: You were able to enroll 516 patients, if I'm reading correctly, in this study, who were brave enough to interrupt their anti-cancer therapy to test getting pregnant. And it highlights a couple of different really important issues. 

One is the bravery and the challenge and the risk that patients take when they enroll in a clinical trial, when they enroll in something investigational. And two: the chance that we take, as researchers ourselves, as the physicians in doing this. Because sometimes these things don't go as planned. 

But you had enough background experience to dive into this. Tell us a little bit about how you got to that point where you were able to say, “Sure, we can do this big study.”

Ann: You know, and, and the other big piece about this highlighting is the altruism of the women because they could have gotten pregnant without us. They didn't need their oncologist in the room. And they were willing to, you know, give us their time and fill out our surveys and show up more. As we all know, clinical trials add a little more hurdles to jump over. 

And at the same time, women wanted to know the answer, too. They wanted to be supported to do this, to answer this question, both for themselves and for future patients coming down, down the lane. 

And so the question though, and how we designed it, because it wasn't a randomized trial, right. Because who would go on that study? You know, you get a baby and you don't? This is not a thing we could randomize to.

And so what we did, through a big international consortium, working closely with a group called the IBCSG or International Breast Cancer Study Group, and the Alliance for Clinical Trials in Oncology, and other groups around the world, we basically worked with our patient advocates and our statisticians to say, you know, what will women tolerate? What do the data tell us is good enough endocrine therapy so we can kind of feel comfortable taking a break and then getting back on? 

Chuck: So where do you go next from here? Is it now going to be a standard clinical recommendation that this approach can be followed? Is this an answered question? Are there still more studies to do? What's next?

Ann: I think the breast cancer community is very much embracing these data and starting to support people, because we had this very good retrospective data. The places where I think people still feel very uncomfortable is, you know, we didn't enroll a whole lot of high-risk people. Only about 6% had stage three disease. And so, we probably need more data there. 

And then of course, the data right now, it's – you know, we had 41 month follow up, it looks really good, but longer term follow up. So we're gonna follow these women for at least 10 years and hopefully it will stay looking as safe as it does today.

And then the other thing is, unfortunately people still do recur. It's just that they don't recur at higher rates than we would've thought. And so we continue to need to kind of step on the gas for this very prevalent type of breast cancer, uh, hormone-sensitive early breast cancer.

Chuck: So potentially endocrine therapy is going to get more intense or it's going to get better at controlling the cancer, which may lead to further questions about pregnancy down the road, perhaps, if endocrine therapy improves. But that would be a sign that the overall outcomes for women with breast cancer are likely getting better.

Ann: You got it. So we're victims of our success. More questions to ask. And I have a lot of patients who had one baby and they want more, and they want to know if that's safe and I’m like, “Well, it’s now what we’re studying, but we can!”

Alicia: Yeah. That's great. That's, that's certainly one of the next questions. You just keep your cohort rolling and say, okay, who wants to have another one? 

Ann: Who wants to go at it again?

Alicia: Yes. Oh, that's wonderful. So, Ann, you see people in clinic all the time with breast cancer. You have a particular focus on that young women's population, who are really in the prime of so many wonderful things in their lives when this happens. How do you approach them now when they come in to see you? That conversation has got to be different. And what hope or what good news do you get to share with them?

Ann: Yeah, so I see a lot of these patients in my clinic, and our whole group here at Dana-Farber – we have a program that supports our faculty and our patients to make sure they're getting all of these, really kind of, new and improved supportive care types of information and resources early on. Because it really can inform their decisions and how they feel about things and how they get through it.

You know, women tell us that the idea of still being able to have a baby really provided them with hope through their whole early stage treatment and beyond. And it kind of gets them to take the endocrine therapy at the beginning because they see the light or the break at the end of that part of the tunnel.

And so I try to come at each of those patients, depending on where they are, with a pretty holistic approach to this. That, you know, our goal is for you not only to survive this breast cancer, but to thrive after it, and to be able to live the most fulfilling life possible. And of course when it comes to things like fertility, that's a really important thing for many of these patients, not everybody, but certainly a large proportion of them.

And being able to plan with them from the beginning: here's how we might accomplish this. It's very gratifying. And I think they feel, this person sees me and they're not, you know, historically it was, let's sideline that. And our, our whole programmatic approach and for individuals, we try to make sure they understand that we get it. 

Chuck: In part, this is the healthy mother effect. Women who have hope that, “I can get through this, I can have a baby. I'm going to get cured of my cancer.” They're going to have a more positive outlook in general. Maybe that's going to lead to better outcomes. You suggest that that's something of a bias in the studies, but it's a kind of a favorable bias, if you will.

Ann: Chuck. I completely agree and I'm going to use that now to say we are harnessing the healthy mother effect.

Chuck: Yes, It's not a, it's not a detractor from the– Yes, exactly. 

Can we zoom out a little bit from breast cancer and just talk about pregnancy after cancer therapy in general? This is very specific to endocrine therapy, hormonal treatments, but what do we know about women with lymphoma, leukemia, survivors of childhood cancer, et cetera, et cetera?  Is there work being done there? And what can you tell our audience about that?

Ann: For all young adult cancer patients and survivors, there is so much work going on, not only to understand and improve the research so that we can inform patients of their risks, of the things they can do to preserve their fertility, of the safety of having babies after breast cancer, both for the moms and for the babies. 

And the good news with most of the other diseases – there are some exceptions – is that we're not so worried about the pregnancy causing a cancer to recur, because usually they're not driven by hormones. We're more worried about the ability to have a pregnancy. And you don't wanna burn a bridge if you don't think about that up front. Because many diseases we need to give people significant amounts of therapy that might make their fertility either thwarted or completely impaired. And so banking, eggs, embryos, sperm is something that we need to talk about from the get-go for a lot of these diseases.

And then in just understanding how older and new therapies do impact on fertility. Because some don't. 

But there's actually a lot of work going on in the policy area trying to push laws through states so that they are supported and resourced to preserve fertility, should they be diagnosed with a cancer at a young age when they are interested in having future children.

So it's really, really, right now a great time to not step back and rest on our laurels because there's been a lot of good work done, but to really step on the gas and push forward on both the research and the getting it into care, and the way to get it into care for everyone is to make sure that our systems support that kind of care. 

Chuck: So when we get together in 12 years for season 14 of The Good News About Cancer, will we be having a reunion of all the children born of these mothers?

Ann: So Chuck, when people ask me what kind of research I do, and they say, you know, tell me about your lab, I say, well, you know, I don't have a conventional lab. The kind of work I do is I count babies. And that is one of the most fun jobs in the world. So yes, I think we should get them together too, to celebrate that. 

Chuck: I look forward to being invited to that event. And Alicia and I can record a live event, maybe interview some of the kids. 

Because, if you're an oncologist and you're counting babies, and you're focusing on breast cancer. You're winning. You've got a great career. You've, you're making a huge impact on not only the patients in front of you, but the patients of the future. And that's really impactful, and great news about cancer.

Alicia: Could not be better. 

Thank you so much for sharing your insights and for sharing with all of us this great news about cancer, about cancer survivorship and these mothers, and also healthy babies that are being born after a really terrible diagnosis. This is absolutely good news about cancer. Thank you.

Ann: Thank you for having me.

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Chuck: Okay, listeners, stay tuned for a very special episode of The Good News About Cancer, season 15, episode one, when we have a picnic and we will record live recording of all of the babies that were born to these women who were receiving breast cancer treatment and got pregnant, and were able to get pregnant during that course of treatment.

Alicia:  What a great thing to look forward to, and there's something else to look forward to: and this is the Cancer Center's Survivorship Research Forum, which is happening on September 18th and 19th, 2025 at Dana-Farber Cancer Institute. We are so excited to be really pushing forward cancer survivorship research, hoping to create more good news about cancer when it comes to survivorship. And we will put a link to this in the show notes from this show.

Thank you so much for listening to The Good News About Cancer. I'm Dr. Alicia Morgans at Dana-Farber Cancer Institute in Boston.

Chuck: And I am Dr. Chuck Ryan at Memorial Sloan Kettering Cancer Center in New York. The views we express on this show are our own and do not represent the views or opinions of the institutions where we work.

Alicia: Thanks to Lilly for support of the show. Our production partner for this series is CitizenRacecar. This episode was produced by Anna Van Dine with post-production by Alex Brouwer.

Chuck: And there's a whole lot more good news to talk about. So make sure you subscribe to this wherever you listen to your podcasts. And if you like the show, share it with someone you think might find it interesting.

Alicia: We will be back again soon with more good news about cancer.