Breast Cancer Podcast

Treatment and Follow-up Care for Premenopausal Women With Breast Cancer

Lidia Schapira, MD; Kathryn J. Ruddy, MD, MPH


May 17, 2022

This transcript has been edited for clarity.

Lidia Schapira, MD: Hello. I'm Dr Lidia Schapira, and I want to welcome you to Medscape InDiscussion: Breast Cancer. Today, we'll be talking about treatment and follow-up care for premenopausal women with breast cancer, a topic that is challenging for all clinicians — not only oncologists but also obstetricians, gynecologists, primary care clinicians, and mental health professionals. Identifying young women at risk for breast cancer and guiding young women diagnosed with breast cancer requires a very special approach. We need to see them through treatment and involve them in making decisions about their treatment that take into consideration the urgency of treating their cancer. At the same time, we need to keep many options open to preserve their future health and happiness as we think about surgical options and systemic treatments.

Before I introduce the guest for this episode, I want to begin with a case study that will help anchor some of our questions and conversation. A 32-year-old nurse comes to see you after being diagnosed with breast cancer. She just got engaged and would like to have children in the future. She self-palpated a small lump. This turned out to be a 2-cm grade 2 invasive ductal cancer that was strongly ER/PR positive and HER2 negative with an Oncotype DX score of 16. She underwent genetic testing and was found to have a MutYH mutation.

Let me introduce my guest, Dr Kathryn Ruddy. Dr. Ruddy is professor of medicine at Mayo Clinic, where she leads the cancer survivorship program and has a practice focused on caring for patients with breast cancer. Dr Ruddy has an extensive research portfolio focused on the natural history and characteristics of young women with breast cancer, novel interventions to improve quality of life for cancer survivors, as well as analyses of costs associated with cancer care. I must add that I've known Dr Ruddy since her fellowship and that we have coauthored 33 publications. I can think of no better partner to discuss treatment and survivorship care of young women with breast cancer. Welcome to the program, Katie.

Kathryn Ruddy, MD, MPH: Thanks so much for having me.

Schapira: Before we begin our conversation, can you briefly describe a time early in your career when you realized that you wanted to focus on this topic and specialize in caring for young breast cancer survivors?

Ruddy: Yes, I first became interested in cancer survivorship when I was a medical student at Penn, and at the time, my best friend was diagnosed with acute promyelocytic leukemia. We were in our early 20s, and now she's a 20-year cancer survivor with three healthy kids. But at the time of that very shocking diagnosis, she was very concerned, understandably, about potential loss of fertility. I started working with Dr Angela DeMichele [at Penn] early on during medical school, which got me interested in breast oncology. Then, I quickly found Dr Ann Partridge working in fertility preservation, and I started working with her at Dana-Farber [Cancer Institute]. I found that I loved that work both clinically and from a research perspective. That was kind of the start of my career.

Schapira: It's amazing. So, my first question is, "How would you approach the conversation about fertility with a young woman who's 32 years old and has just been diagnosed with breast cancer?"

Ruddy: I actually had a very similar situation in clinic yesterday. I think it's so important that all patients who haven't completed their desired childbearing at the time of the cancer diagnosis see a reproductive endocrinologist as soon as possible. In the case that you presented, it sounds like the patient has maybe already had a breast surgery. But theoretically, it's ideal to send patients to reproductive endocrinology as soon after the diagnosis as possible, even before surgery. And I think for this young patient, even though it looks like she doesn't need chemotherapy based on that low Oncotype DX score, she still might want to consider egg harvesting. With our adjuvant endocrine therapy, she's going to experience some natural ovarian aging even outside of having cancer. Now, something that's changed quite a bit over the last decade is that many young women in their 30s are freezing their eggs even in the absence of a cancer diagnosis to allow more reproductive options.

Schapira: How would you use that Oncotype DX score in thinking about adjuvant therapy?

Ruddy: I use Oncotype DX widely, and I think it's useful across a broad age spectrum. I looked recently at the TAILORx trial publication; there were women even as young as 23 enrolled in that study. So, I think we can use Oncotype DX to help us feel comfortable not giving this young woman chemotherapy. I would recommend adjuvant endocrine therapy for her, but not adjuvant chemotherapy, given that her tumor was small, the node was negative, and her Oncotype DX score was only 16.

Schapira: Holding on to the idea of women who may need chemotherapy, if there is a woman who has an endocrine therapy–unresponsive tumor or very high Oncotype DX score, what do you do, or what can we do, to help preserve her fertility if she is going to have chemotherapy?

Ruddy: Egg freezing is my number-one choice. So obviously, I would say immediate referral to reproductive endocrinology to consider oocyte cryopreservation, embryo cryopreservation, or sometimes both. If a patient doesn't opt to undergo that, or even if she does, I think we can consider the use of gonadotropin releasing hormone agonists, as well. The POEMS trial data, as you know, showed that women with estrogen receptor–negative tumors who used goserelin at least a week prior to their first dose of chemotherapy and then during chemotherapy were more likely to go on to become pregnant than those who didn't receive that gonadotropin-releasing hormone agonist. We think this is likely because the gonadotropin-releasing hormone agonist was ovarian protective in this setting. So, I do think [goserelin] is a possibility, but I don't think it should be relied upon if egg freezing is considered by the patient as a viable option from a financial standpoint. I do recommend [egg freezing] be pursued.

Schapira: Going back to women who may benefit from endocrine therapy, such as the patient in our case, what type of endocrine therapy do you recommend? How do you think about it both in terms of the kinds of agents used and the duration? This is another very pressing question in these cases.

Ruddy: For this patient, with a 2-cm node-negative tumor at a very young age, I would probably be tempted to consider trying tamoxifen, maybe with a gonadotropin-releasing hormone agonist if she were willing to take on more side effects from her treatment. We know that from the SOFT trial data, patients younger than 35 did have substantially better with disease-free and distant recurrence-free survival if they received a gonadotropin-releasing hormone agonist in addition to tamoxifen. I think if this patient could tolerate that combination, it's probably optimal. I would say an aromatase inhibitor with ovarian function suppression is probably more than she needs for this small tumor. And if she can't tolerate it, which many women can't — the gonadotropin releasing hormone agonist, as you know, has a significant toxicity in terms of vaginal dryness and hot flashes and other issues — then tamoxifen alone for 5 years would also be very reasonable. In her case, with her interest in pregnancy, it may end up that she doesn't want to do all 5 years. She may be somebody who's thinking about coming off adjuvant endocrine therapy for some time, and this may play into wanting to be a little more aggressive with the addition of the gonadotropin-releasing hormone agonists, at least up front.

Schapira: So, how do you weave these two threads together — the conversation about adjuvant therapy, fertility, desire for a biological child, and the timing?

Ruddy: Have the conversation upfront about when she thinks she wants to try to start her biological childbearing in the absence of cancer. And then how might the cancer treatment fit optimally into that? What kinds of possible delays on her optimal childbearing age would she be willing to accept? If she were really hoping to get pregnant a year from now, I would be talking with her about getting going on the adjuvant endocrine therapy, and then when she might take a break to try to become pregnant.

Schapira: Can you tell our listeners a little bit about the POSITIVE trial?

Ruddy: Yes, this is a really exciting and important study. More than 500 women around the world enrolled in the POSITIVE trial to assess the safety of taking a break in adjuvant endocrine therapy for an attempted pregnancy. These were women who had been on adjuvant endocrine therapy between 18 and 30 months, and that could have been tamoxifen alone or any type of adjuvant endocrine therapy was allowed after the 18 to 30 months of upfront adjuvant endocrine therapy. They took a break. They attempted pregnancy, and what we're waiting for and hope we will get pretty soon are data to say how often they became pregnant and how many [breast cancer] recurrences happened in relation to the pregnancies. The women, after they became pregnant or finished their pregnancy attempts, were encouraged to go back on their adjuvant endocrine therapy to complete their planned full duration of treatment. So, we're hopeful we won't see any detrimental impact of taking this break on breast cancer–related outcomes. I think it will be important to see these data hopefully soon.

Schapira: You bring up a very important point, and that is the safety of becoming pregnant after having breast cancer. Of course, there will never be a randomized controlled trial, or registration studies such as the one you've just described will be very important. Until we have those results, can you tell us if, in your perspective, it is safe and if you reassure patients that it is safe?

Ruddy: Yes, I think we have lots of data, not from randomized trials, as you said, but from large cohorts to show that women who do become pregnant after breast cancer do not have a higher risk of recurrence than those who do not become pregnant. So, I feel it's relatively convincing that becoming pregnant does not increase risk of recurrence regardless of tumor biology. That's true of women with estrogen receptor–positive tumors and estrogen receptor–negative tumors. I'm very supportive of survivors pursuing pregnancy for that reason, in addition to obviously wanting to be supportive of this as a very important quality-of-life issue. I do think that we can be relatively optimistic with our patients who are desiring future childbearing — that this should be something they can pursue, and that fertility preservation techniques at the time of diagnosis can help make it a reality.

Schapira: Let's talk a little bit about quality of life. You mentioned that for some young women, ovarian suppression, for instance, is intolerable. How do you track the symptoms of the cancer survivors, both those on endocrine therapies and those who are off treatment?

Ruddy: This is a very important issue, and we know that young women, especially if they're receiving gonadotropin-releasing hormone agonists that put their ovaries to sleep, are experiencing some significant side effects. We know from the SOFT trial data that we saw quite different rates of various toxicities between the arms of the trial. As you know, the SOFT trial included a randomization to tamoxifen alone, tamoxifen with ovarian function suppression, or exemestane with ovarian function suppression. Certainly, the use of the gonadotropin-releasing hormone agonist increased things like vaginal dryness and hot flashes. And so, in my practice, I talk about sexual functioning, which can be very much impacted by the vaginal dryness issues with ovarian function suppression. We also have the development of tools that can help us assess patients in between visits. Patient-reported outcomes, which often comprise surveys that patients can complete between visits, can help us keep a better eye on how our patients are doing at home and what we might help them with. Sometimes, we can tie those patient-reported outcomes to educational materials and encourage patients to reach out to us if those are not adequate for symptom management.

Schapira: Basically, you're using some version of electronic patient-reported outcomes, and then you push out some customized materials. How's that working for you?

Ruddy: We have one really exciting effort across all of medical oncology at our Mayo Clinic in Rochester and Midwest Health System sites that's not specific to breast cancer. It's a cluster randomized trial funded by the National Cancer Institute. The principal investigator of this study is Dr Andrea Cheville, who's one of our Physical Medicine and Rehabilitation doctors, and she's assessing six symptoms that are not directly linked to a particular cancer or a particular treatment. The symptoms are physical dysfunction, sleep, pain, anxiety, depression, and fatigue. Patients are asked to report on their level of each of these six symptoms on a zero to 10 scale before every medical oncology visit. In response to those reports, they receive just patient educational materials if they score four or higher on any of those symptoms; if they score seven or higher, they're offered a phone call from one of our nurse symptom care managers, physical therapists, or social workers, depending on the symptom of concern. It's really exciting. I can't tell you any of the data yet coming back in terms of the results of the intervention and whether this is actually reducing symptoms. But I can tell you I've received a lot of really positive feedback from my patients on the benefits of having that connectivity and symptom response. I think this is the way of the future to expand beyond those six symptoms to be able to really understand how our patients are feeling. I should also mention that part of this is also a survey that goes out in between visits. Patients being cared for solely in our practice, also receive monthly surveys. So, we are able to then see how their symptoms trend over time in between our visits. I think this is really exciting.

Schapira: I share your enthusiasm and look forward to seeing how this works. It certainly seems to me to be a very good way of maintaining that connection that patients find so helpful. And also in this era of connectivity and telehealth, it allows us to have a far greater reach for patients who perhaps find it difficult to come to see us or who may otherwise not think of calling before they crash. And then we tell them that we wish they had come to us sooner. So, this sounds like a wonderful line of research, and I'm sure we all look forward to seeing more of it. How often do you prescribe nonpharmacologic therapies for your cancer survivors? I'm thinking specifically about acupuncture, mindfulness techniques, yoga, and exercise.

Ruddy: I try to talk about exercise in every visit. I think it's really important for management of symptoms, possibly for reducing risk of recurrence, and for optimizing quality of life. Now, thinking about other types of integrative therapies, they can also be really valuable, especially for patients who are already interested in mindfulness and yoga or who have some experience with these techniques. I think that for a lot of patients, they can be very, very beneficial.

Schapira: Before we return to our case, I have a last question, and one I've asked you many times informally, so we can now get you on the record: How do you integrate at Mayo the referral back to primary care for women who are at low risk of recurrence?

Ruddy: We actually have a very unique model at Mayo Clinic that I know you and I have talked about before. Our patients who have low-risk cancers — low risk enough that we don't treat them with chemotherapy — often transition almost immediately out of medical oncology to our internal medicine–led breast clinic. This is a clinic that often sees our patients initially before they even get to medical oncology. Most patients will come into Mayo Clinic via this internal medicine–led breast clinic. So, it's a very natural transition for them to then return to that clinic for their follow-up, physical exams, breast imaging, prescribing of their adjuvant endocrine therapy, and management of endocrine therapy side effects. The clinic is staffed by a truly remarkable team of nurses, advanced practice providers and physicians who have tremendous expertise in the care of this population. I wouldn't say that they are primary care providers. They really are breast cancer experts, but they're internists rather than medical oncologists. Many patients will only see a medical oncologist once, and then they will be seen by these internists for the remainder of their adjuvant endocrine therapy course. The transition back to primary care often happens at the end of the adjuvant endocrine therapy course. Other patients, particularly those who have to travel quite a way to get to us, might decide to transition to primary care instead of making the transition to the internal medicine breast clinic. And we certainly support that. Then, if that's going to be the patient's preferred follow-up strategy, I'll often reach out directly to their primary care provider to have a warm handoff of their care, but I certainly think it is very appropriate for many patients, as well.

Schapira: Thank you so much, Katie. Let's come back to our case. The 32-year-old nurse who is engaged and wants to have a family — we've already decided we're not going to recommend chemotherapy for her. She also undergoes genetic testing, which is something I wanted to include to remind our listeners that anybody diagnosed in this age group should have genetic testing. And as often happens, we find something that is important but not necessarily known to guide our therapy; in this case, it is a MutYH mutation. So, we're going to recommend that she gets colonoscopies and so on, but it's not going to directly affect her breast management. What advice would you give to her if she comes to you as a patient?

Ruddy: I think there is currently an open trial through the Alliance aiming to improve persistence and adherence with adjuvant endocrine therapy, so enrolling in that study might be an option for her. I would also talk to her about the importance of other pieces of survivorship care. Assuming she's had a lumpectomy and has residual breast tissue, she is going to need annual mammograms, depending on her breast density. She might also benefit from supplemental breast imaging, and this usually comes up in my visits. What else is needed? Do I need other types of imaging? Do I need blood work? I would certainly assure her that I wouldn't be recommending any routine blood work in the absence of symptoms, but she does need a history and a physical exam. At Mayo, we usually recommend that this be done twice annually for the first 3 years of follow-up and then either once or twice annually until the completion of adjuvant endocrine therapy. I think she's very likely to do very well. I think her risk of recurrence from breast cancer is relatively low, and I would reassure her of that.

Schapira: Thank you very much, Katie, for your very wise approach to this case. I think we've covered a lot of important issues, including the initial evaluation and management, treatment options, and the importance of symptom management during survivorship.

Ruddy: Thank you so much, Lidia, for asking me to speak with you and for covering this important topic.

Schapira: Thank you, Katie, and thank you to the listeners. This concludes our program for today.


MutYH Mutation Carriers Have Increased Breast Cancer Risk

Kathryn J. Ruddy, MD, MPH Biography

Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer

About Oncotype DX Breast DCIS Score

Goserelin for Ovarian Protection During Breast-Cancer Adjuvant Chemotherapy

Adjuvant Ovarian Suppression in Premenopausal Breast Cancer

Who Are the Women Who Enrolled in the POSITIVE Trial: A Global Study to Support Young Hormone Receptor Positive Breast Cancer Survivors Desiring Pregnancy

Pregnancy After Breast Cancer

Pragmatic Cluster Randomized Trial to Evaluate Effectiveness and Implementation of Enhanced EHR-Facilitated Cancer Symptom Control (E2C2)

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