Fertility Preservation And The Risk Of Breast Cancer Recurrence
Editorial Comment: Few of us have not seen women with newly diagnosed breast cancer who have undergone fertility treatment in the past and wondered whether it affected the likelihood of a breast cancer diagnosis. Whereas this study does not examine the effects of fertility treatment in the distant past, it does query the impact of fertility preservation on prognosis after a breast cancer diagnosis and before treatment.
The hormonal stimulation of the ovaries required for embryo cryopreservation requires approximately 14 days when serum estradiol attains 10-20 times higher levels than that seen during the normal menstrual cycle. The safety of fertility preservation (FP) has previously been inferred from the safety of pregnancy following breast cancer treatment, in which estrogen levels reach levels 100 times that during the normal menstrual cycle. However, hormonal stimulation in the face of untreated breast cancer is hardly comparable to pregnancy with no known active disease. A recent study by Letourneau et.al., (Cancer 126:487-95) addresses this issue.
The study population included patients diagnosed with breast cancer and referred for FP to the Reproductive Endocrinology Clinic at the University of California, San Francisco (UCSF). Those patients who did not pursue FP resumed care with their oncology team and served as the control group. Those who chose FP began ovarian stimulation as soon as possible after the initial consultation. Follicle-stimulating hormone and human menopausal gonadotropins were used for ovarian stimulation. Patients with ER-positive tumors were co-treated with letrozole or tamoxifen during this time. Disease-free survival (DFS) was the primary endpoint.
Three hundred twenty-nine women were included in the study. In total, 207 women had egg or embryo cryopreservation before cancer treatment, and after consultation, 122 did not choose to have FP. The median follow-up was 43 months (2-131 months). In examining the two groups, those that underwent FP had characteristics suggestive of a more aggressive disease. Those women choosing FP tended to be younger, more likely to require chemotherapy, and have greater than Stage I disease. Patients undergoing FP tended to be younger, more likely to require chemotherapy, and more likely to have greater than stage I disease. One could conclude that although women undergoing FP had more aggressive disease, FP was not associated with a decrease in disease-free survival. Over the 43-month median follow-up, 22 women developed a disease-free survival endpoint. Nine patients developed a locoregional recurrence, 12 developed distant metastases, and 1 developed a new primary. Univariate statistical analysis showed that outcomes were similar between those undergoing FP and those that did not (93 vs 94% respectively). The relationship remained the same when controlled for age, stage, or whether chemotherapy was given. Using similar adjustments, disease-free survival remained the same in patients having neoadjuvant chemotherapy.
The authors concluded that “We have demonstrated that patients who chose to undergo FP were similar to those who did not in terms of disease and treatment type. With rare exceptions, we recommended consideration of FP (oocyte or embryo cryopreservation) to each patient. In fact, since those who underwent FP were 2 years younger at diagnosis and were more likely to have greater than stage I disease, one could argue that women who underwent FP had a slightly more aggressive pattern of disease at presentation”.
Dr. Alan Stolier, MD, FACS, clinical breast oncologist, shares his expert medical perspective with a series of educational and scientific articles.