Fertility after Breast Cancer
ARLINE KALLICK: Thank you. Hello everyone, and welcome to the Breast Cancer Network of Strength ShareRing Network National Teleconference. Tonight’s call is also in partnership with the Young Survival Coalition and Fertile Hope. Our call will begin with tonight’s speaker, Dr. Karine Chung. Dr. Chung is Assistant Professor in the Division of Reproductive Endocrinology and Infertility at the University of Southern California Keck School of Medicine. She is an active member of the American Society for Reproductive Medicine, the Fertility Preservation Special Interest Group, and the American College of Obstetricians and Gynecologists. The current research, among other things, is the study of breast cancer and its relationship to reproduction, the safety of pregnancy after breast cancer, prevention of breast and ovarian cancer, and refining techniques of egg and ovarian tissue freezing. She has presented multiple invited lectures on the topic of fertility preservation in cancer patients. We’re very happy to have her with us this evening.
Please begin, Dr. Chung, and welcome.
DR. KARINE CHUNG: Thank you so much Arline, and thank you so much for inviting me to take part in the teleconference tonight. It’s an honor and a pleasure to speak to you all on the topic of fertility after breast cancer. It was not too long ago that this was not considered an important topic, mostly because pregnancy was assumed to be bad for women with breast cancer and doctors were telling their patients that having children after breast cancer was not really an option. So we now know that this isn’t true. And as our societies tend to delay having children until later and life continues, more women are going to be diagnosed with breast cancer before they’ve either started or completed their families. And these women will all be faced with the decision of whether or not to try to become pregnant after breast cancer. So about how many women are faced with this decision? Well, a recent report shows that about 200,000 women per year are diagnosed with breast cancer in the United States alone, and 25% of these cases, this means about 50,000 women, are diagnosed in their reproductive years. And we consider reproductive years anywhere between the ages of 18 and 45. Breast cancer is the most common cancer to affect women in this age group. And so how important is the topic of fertility among breast cancer survivors? Well, I think it’s very important, and most of you probably agree, otherwise you wouldn’t be participating in this conference tonight. But a recent study also supported that in the Journal of Clinical Oncology. There was a web-based survey of 657 breast cancer survivors, all less than 40 years old; 56% of them wanted to have children in the future, and 73% reported concern about the possibility of becoming infertile after the cancer treatment. I think we’ll all agree that this is a very important topic amongst breast cancer survivors.
Knowing this I think it’s important to be aware of the potential impact of breast cancer treatment on future fertility. And while chemotherapy is one of the primary reasons that survival rates after breast cancer have been, has improved so much over the recent years, it’s without question associated with the detrimental effect on fertility.
In trying to understand why fertility declines after cancer therapy, it’s first important to understand that there is a natural decline in fertility that occurs with a woman’s age. Many of you probably already know that all women are born with a limited supply of eggs, and over time we will all run out. Each egg is contained in a fluid-filled structure called a follicle, and the follicles are all packed within the ovary. On average each woman is born with about two million follicles, each containing a single egg. And by puberty the average number of eggs is already down to about 200,000. The body sort of randomly selects eggs and decreases the number. By age 37 it’s down to about 25,000, and then declines very rapidly after that until we reach menopause. At the time of menopause there are about 1,000 eggs left, which still seem like plenty of eggs. But the problem is that the number of eggs, as the number of eggs decreases the quality of eggs also decreases. Egg quality is not an easy thing to conceptualize; we can’t actually judge egg quality by looking at eggs. But the one good way to think about egg quality is the ability of the egg to do all it needs to do to become a baby. That means the egg needs to fertilize, it needs to develop into an embryo, and then it needs to implant. So older women have a harder time getting pregnant because of reduced egg quality. And the theory is that these eggs do not have sufficient energy to perform all the functions necessary to achieve pregnancy.
Now switching our focus a little bit to why fertility declines after cancer therapy. It turns out that the ovarian follicles and eggs are really vulnerable to agents that cause DNA damage. This includes both radiation and chemotherapy. The end result of cancer treatment is that you have a dramatic reduction in the supply of eggs due to a process we call in the medical field cell death. The ovaries really shrink down in size and really start to look like menopausal ovaries, mostly because the number of eggs is still dramatically reduced. The effective cancer treatment on egg quality is not entirely clear but since we know that most patients who are undergoing cancer treatment, especially if tamoxifen or other hormonal treatments or plan, there’s going to be a delay before they can start trying to get pregnant. That delay is going to cause an age related decline in eggs, in egg quality, even if the cancer treatments don’t directly cause a decrease in egg quality. Which factors influence fertility potential after cancer therapy? The main factors include age at treatment, and the type and dose of chemotherapy that’s used. As far as age is concerned, the older a woman is at the time that she’s diagnosed with cancer and undergoes chemotherapy, the more likely she is to become infertile afterwards. As far as the type and dose of chemotherapy agents are concerned, the higher the does of the agent, the more likely you are to suffer infertility. And for the type of chemotherapy, the ones that are really infamous for calling infertility are the alkylating agents like cyclophosphamide or ifosfamide. Other high-risk agents include melphalan, busulfan, nitrogen mustard, chlorambucil, and procarbavine. Agents that are considered intermediate risk are Cisplatin, Adriamycin, and Pacletaxel.
Other effects, other factors that will affect fertility as far as cancer treatment is concerned are radiation, the dose of radiation; higher doses will result in a greater loss of eggs. The location of the radiation field really makes a big difference. So direct radiation to the pelvis or abdomen where the ovaries are are much more likely to result in infertility as opposed to radiation that is concentrated on the breast. The pretreatment status, fertility status of the patient also makes a difference because it makes sense that if a patient was sub-fertile prior to her cancer therapy, she’s more likely to suffer infertility after her cancer therapy. Whether the type of cancer makes a difference as far as the potential for infertility after treatment is somewhat controversial. There is a study that suggests that patients with Hodgkin’s lymphoma do worse. There’s another study that suggests that breast cancer patients are more likely to suffer infertility. But overall it seems that the type of cancer probably makes very little difference as far as fertility potential in the future is concerned. The two main factors are A, the treatment, and type and dose of chemotherapy agent. How often do these treatments impact fertility? Most of the studies report rates of amenorrhea; that means lack of menstrual periods. And rather than testing fertility, so this is sort of a marker for fertility, but is not a perfect marker, which we’ll talk about in a minute. But after some of the common chemotherapeutic regimens for breast cancer, including CMF, which is Cylophosphamide, Methotrexate, Fluorouracil. The studies range a lot so for, in — amenorrhea rates range between 20 and 100% after this regimen, and the average is about 68%, so quite high.
Anthracycline with cyclophosphamide and paclataxil called ACP is associated with 50% rates of amenorrhea after treatment, which is also quite high. Anthracycline and cyclophosphamide alone is associated with about a 34% rate of amenorrhea, and so that’s a little bit lower. And of course, the dose, the regimen has to be effective against the breast cancer, but also keeping in mind that certain agents are more likely to cause amenorrhea than others. So the rates of infertility are probably actually much higher than the rates of amenorrhea, since many women who resume periods will still have very seriously impaired fertility. We know that because in the transition into natural menopause, menstruation is really the last thing to go. The eggs will lose the ability to fertilize and implant many years before the periods actually become irregular.