Fertility and early menopause after cancer can pose challenging emotional and medical issues for patients and their clinicians. Survivors who become infertile because of their cancer treatment are at an increased risk for emotional distress and are often affected by unresolved grief and depression, according to Ann H. Partridge, MD, MPH, Medical Oncologist, Dana-Farber Cancer Institute, Boston.
“Like in many aspects of breast cancer care, patient preference is critical,” Dr Partridge said at the 2015 Breast Cancer Symposium. “For us as clinicians, managing expectations is often necessary. We need to address fertility issues up front and include fertility concerns in the risk-benefit analysis. We need to address side effects, both physical and emotional, of premature menopause in both long- and short-term follow-up, and ultimately, we need to continue to support our patients and support research in this area.”
Among 657 women (median age at diagnosis, 33 years) who responded to an online survey, 57% reported substantial concerns about fertility after their breast cancer treatment, and 29% reported that fertility concerns had influenced their treatment decisions.
“This was a wake-up call for a lot of clinicians,” said Dr Partridge. “Patients may not be taking their tamoxifen or may be passing on adjuvant therapy due to fertility concerns.”
These concerns are becoming increasingly prevalent as a result of the rising average age of first births around the world. In 1970 in the United States, the average age of first birth was 21 years; it is now 25 years. (In the Netherlands, Japan, and Switzerland, the average age of first birth is >29 years.)
“More women are waiting to have children,” said Dr Partridge, “and breast cancer incidence increases, even in this young cohort. We treat our patients with good intentions, but this can threaten their future fertility.”
According to Dr Partridge, the risk for amenorrhea, which is the best indication that clinicians have in regular practice for infertility, is directly related to age and treatment. However, studies assessing how long women remain amenorrheic after chemotherapy are limited.
Even in women who remain premenopausal after chemotherapy, fertility may still be impaired, said Dr Partridge. In a study of women who remained premenopausal after chemotherapy, survivors had statistically worse ovarian reserve compared with a control population.
The American Society of Clinical Oncology’s recommendations for preservation of fertility include:
- Oocyte or embryo cryopreservation
- Cryopreservation of ovarian tissue
- Ovarian suppression with luteinizing hormonereleasing hormone agonist through treatment
- Oocyte donation or gestational surrogacy.
“The most important thing is to communicate with our patients about this,” said Dr Partridge. “It’s important to allow the woman be a part of these decisions and ultimately make the choice.”
A recent study showed that, for young women with breast cancer, ovarian suppression is correlated with disease-free survival (Francis PA, et al. N Engl J Med. 2015;372:436-446).
“There may be risks to remaining premenopausal,” said Dr Partridge. “We really need to individualize treatment to the patient who actually wants a baby.”
Finally, there is a need to consider the risk for pregnancy itself. The conventional wisdom, Dr Partridge noted, has been to wait until the highest risk for recurrence is over (usually the first 2-3 years after diagnosis), but in patients with estrogen receptor–positive disease, that risk can last for nearly a decade.
To this end, the POSITIVE trial, a phase 2 trial designed to evaluate safety and pregnancy outcomes of interrupting endocrine therapy for young women with estrogen receptor–positive disease who desire pregnancy, is currently recruiting.
“We’re going to answer this question, at least in a phase 2 way,” Dr Partridge concluded.