In this interview we discuss the causes of treatment-related infertility as well as strategies to preserve fertility in patients treated for their breast cancer.
Ann H. Partridge, MD, MPH
Ahead of the 2015 American Society of Clinical Oncology (ASCO) Breast Cancer Symposium, held September 25–27 in San Francisco, we spoke with Dr. Ann H. Partridge, associate professor at Harvard Medical School and founder and director of the Program for Young Women with Breast Cancer as well as the director of the Adult Survivorship Program at the Dana-Farber Cancer Institute in Boston. Dr. Partridge will be speaking at the Symposium about fertility issues-including early menopause-that young women face after a breast cancer diagnosis.
- Interviewed by Anna Azvolinsky
Cancer Network: What are the major fertility concerns that premenopausal women face when they receive a breast cancer diagnosis?
Dr. Partridge: Thank you for focusing on this. When a premenopausal woman, particularly a young woman who has not completed her family, is diagnosed with breast cancer, that woman faces not only the concerns that everyone faces when they are diagnosed with breast cancer, but she may also want to have babies in the future-and sometimes they are also pregnant when they are diagnosed (rare, but it happens). That brings up several other issues and concerns about how we can help that woman to live the fullest life after breast cancer-so not only survive the breast cancer, but be able to go on and reproduce if she is interested in having biologic children. This is a huge issue for this relative minority group of patients, meaning young patients diagnosed with breast cancer.
Cancer Network: Are there specific drugs or treatments that can particularly affect a woman’s fertility or is this a risk for any type of intervention?
Dr. Partridge: It is interesting in that there are a lot of misconceptions out there, and I will go through these one by one. First, breast cancer in and of itself-assuming that a woman survives-does not impact fertility. So, the breast cancer is generally not affecting the ovaries or reproductive health. It can have an impact on nursing, but it’s not like ovarian cancer where it’s affecting the ovaries and can make you infertile. If you are really sick from breast cancer, you will likely be less fertile because illness can make someone infertile, but generally the breast cancer itself does not make one infertile or less fertile.
But what does impair or threaten to impair fertility are two major things. One is chemotherapy. Standard cytotoxic chemotherapy for breast cancer tends to damage the ovaries and most of the regimens we use for breast cancer do appear to cause ovarian toxicity to some degree. The degree of fertility impairment, or at least the premature menopause that you see as a surrogate, varies by the amount of therapy given and the specific regimen, as well as the age of the woman at diagnosis.
The second big factor, and this is sometimes the biggest factor, because many women won’t go into menopause right away with chemotherapy, and would still likely be fertile, is the time it takes to receive appropriate endocrine therapy. So hormonal therapies (tamoxifen, ovarian suppression, now more and more aromatase inhibitors), we give those therapies for, on average, 5 years, and now we are giving tamoxifen for 10 years, based on newer data. During that time it is not that ovarian function is specifically damaged-it’s changed and suppressed or modified in the short term, but not permanently changed by these drugs-but what limits fertility at this time is the aging a woman is going through. So, all women become less fertile as they age, and that is no different in a breast cancer survivor, and while they are on these drugs their ovaries are naturally aging-it doesn’t set the clock back, even when the ovaries are suppressed, because there is a natural aging phenomenon that continues.
So for many young women, they get the chemotherapy, their ovaries are still functioning, they are good candidates to go on and become pregnant if they want to, and then they are stuck taking hormonal therapy. I say, “stuck,” but at the same time, that is one of the best treatments we have to reduce the cancer recurrence risk in hormone-sensitive breast cancer. So it becomes very tricky to find the happy medium to allow a woman, especially a woman who is older at diagnosis and wants a baby, but also wants the best breast cancer care. It can be a real negotiation for that woman, saying, “OK, how much risk is the cancer, and what do I need to do to reduce that risk? And do I want to take the full package of chemotherapy, hormones if that is the right thing for the risk, or do I want to modify that a bit because I want to try to have a baby sooner or have a baby at all?”
Cancer Network: What are some of the fertility options for these women?
Dr. Partridge: In terms of preserving fertility, what I always like to remind my junior colleagues and fellows and trainees is that we do a lot of breast cancer treatment that is aimed at overtreatment. And I don't mean that in a bad way. We give treatment to 100 patients and we know that it is going to help only 3 to 5 of them-it’s just who are those 3% to 5% that will get the benefit? We don't know that all the time. So, it is not a bad thing to do it as long as a woman is informed, because it is preventing a really bad outcome. But sometimes you step back and say, this woman’s risk is not that high for recurrence and her desire to have a baby now or in the near future is really strong and the incremental benefits of chemo or taking tamoxifen for a longer period of time are small.
So the first and foremost thing I always try to remember in these discussions is how much does the woman really need the therapy that may damage her ovarian function and/or make her take a lot of time before she can try to get pregnant? Because time limits ovarian function. So the first thing is can you spare the woman the hormonal therapy? Does she really need it? Unfortunately, sometimes women absolutely need the chemotherapy and the hormonal therapy, and younger women often need it more because the diagnosis is of a higher risk disease. So usually the answer is yes, but how can we preserve fertility and still give the patient the best therapy?
Treatment options for fertility preservation fall into a few classes. First, what has been well established for many years is to preserve embryos prior to treatment. So a woman gets diagnosed, she is still fertile, and you send her to the reproductive endocrinologist, she goes through a short course of ovarian stimulation and they get oocytes and those oocytes get fertilized in a test tube-classic IVF. You need a sperm donor or partner for that. If a person doesn’t have a partner or doesn't want to go to a sperm bank, the other option is to just freeze oocytes. Up to 2012, that was considered experimental, but the good news is that the freeze-thaw process and the ability to make babies from frozen eggs has been much more successful and that has moved to a non-experimental class and is another option for patients-in particular for single and younger women who are not yet thinking about a partner or don't want to go to a sperm bank yet.
Another method that has been around for a while, and there have been a number of studies that have looked how well it works, is suppressing the ovaries through chemotherapy. We use drugs called gonadotropin-releasing hormone (GnRH) analogs that can suppress the ovarian function through treatment. There are now a number of randomized trials and the most recent and large and robust of which has suggested that it does indeed preserve ovarian function and menses. The long-term fertility outcomes are harder to get. There is a suggestion in at least two of the larger studies that there are more babies born to those women who had their ovaries suppressed, but that needs to be taken with a grain of salt as the data are not terrific. But that is an easier option for women, and it can be used to suppress the ovaries for anyone getting chemotherapy, although it adds a few side effects.
Those are the main options and there are more experimental things on the way, including taking a piece of the ovary and freezing that. That has a limited track record so far, but there is lots of research going into that. In a breast cancer survivor, though, the likelihood of needing that is not very high, because in breast cancer we don't completely ablate ovarian function. So in most people with breast cancer, they have a little bit of time and can go through IVF or the ovarian-inhibition procedure. Those are the main options for fertility preservation for women.
Cancer Network: Lastly, what do you see as the role of the women’s clinicians, particularly the medical oncologists, in providing patients with information about her fertility options?
Dr. Partridge: I think the role of oncologists in this is critical. First, if you don't ask the patient if they are interested in fertility, sometimes they won’t tell you or won’t realize that the treatment can impair their fertility. They may be so caught up in surviving their breast cancer and fearful, and may not understand the risks of the therapy, that they may not tell you. So when treating a young woman, you can never assume that a woman is done with children even if she already has one. As a second child, I firmly believe that.
Sometimes having another baby is not an option or sometimes people change their mind once diagnosed, but you have to give them the option. And if it is something they want to consider, it is imperative that the patient and oncologist think about what the risks are to the patient’s fertility, and then either talk to the patient about fertility preservation or send them to someone who is knowledgeable and can do that. It is critical to talk about it, and then appropriate from a disease and treatment standpoint to offer them fertility options and preservation choices if it is feasible. Sometimes it’s not feasible and having that discussion is critical.
As oncologists, we are used to having tough conversations with our patients. We talk about life and death all the time and losing your fertility for some of these women feels like a death, and we need to acknowledge that, need to help our patients get through that and understand that you really do need the breast cancer treatment, and this is a huge loss, or this is a loss we can fix through fertility preservation, or possibly fix. We help our patients tremendously just by talking about it and allow the patient space to do something about it or grieve that loss and get them psychosocial support that’s needed if that is something that is burdensome for them emotionally.
Another thing is that the oncologist doesn’t need to do it alone as there are specialists who focus on reproductive health. Of course not every center has access to them, but you can get help with that. There are online resources for patients. It is really one of the things that should be part of informed consent when discussing chemotherapy treatments.
Cancer Network: Thank you so much for joining us today, Dr. Partridge, we’re looking forward to your presentation at the meeting.
Dr. Partridge: Thanks, my pleasure.