Disease-Free Survival Does Not Differ According to Fertility Preservation Technique for Young Women With Breast Cancer

Abstract

ABSTRACT Approximately 5% of breast cancer cases occur in women younger than 40 years, and the 5-year overall survival for women between the ages of 15 and 44 years is 90%. As the childbearing age increases, so too does the proportion of women who wish to achieve pregnancy after breast cancer. The conception rate among these women is 40% lower than the general population, as a result of advanced age and the gonadal toxicity of chemotherapy. Fertility preservation (FP) techniques enable young patients to freeze gametes before treatment; however, the most recommended method of FP is oocyte or embryo vitrification after controlled ovarian hyperstimulation (COH), which has limited safety data in breast cancer patients. This retrospective cohort study aimed to evaluate disease-free survival (DFS) in a large cohort of women with breast cancer who underwent FP techniques with or without COH. Patients with breast cancer between 18 and 43 years old referred for FP to 2 university hospitals between July 2013 and July 2019 were included. Women not included in the FP program after oncofertility counseling, those with stage 4 disease at diagnosis or history of other invasive cancer, or those with gonadotoxic treatment have been excluded. Patients were split into 2 groups, with the STIM group receiving at least 1 COH protocol using a gonadotropin-releasing hormone antagonist with or without an aromatase inhibitor and the no STIM group not undergoing ovarian stimulation. Patient characteristics, obstetric variables, and oncology characteristics were collected from medical records. Disease-free survival and overall survival were estimated using Kaplan-Meier plots and compared between the 2 groups by log-rank test. A total of 740 women (76.7%) who attended oncofertility consultations for breast cancer were included. Of these, 328 (44.3%) underwent at least 1 ovarian stimulation cycle, and 412 (55.7%) had an FP technique without exogenous FSH administration. The STIM group was significantly older and had lower values in ovarian reserve tests, and more women in the no STIM group underwent a mastectomy and neoadjuvant chemotherapy. The proportion of patients with hormone receptor-positive tumors was equal in both groups. Letrozole was coadministered with exogenous gonadotropin in 39.3% of women in the STIM group (Let-COH). Overall, 16.8% of patients had a tumor still present on oocyte retrieval after COH, of which 55% received a Let-COH protocol. Follow-up data were available for 80.9% (559/740) of patients. Cancer recurrence was documented in 87 patients (27 in STIM, 60 in no STIM), and DFS was not statistically different between the groups (log-rank test P = 0.09). Neither difference in DFS nor overall survival was observed in the Let-COH group compared with those undergoing COH after breast surgery. Kaplan-Meier estimates of overall survival at 4 years were 97.6% in the STIM and 93.6% in the no STIM groups, and after adjusting for prognostic parameters, the risk of death remained significantly lower in the STIM group (hazards ratio, 0.55 [0.35–0.85]). The results of this large retrospective cohort study demonstrate that the use of COH for FP patients with breast cancer before or after breast tumor surgery is safe; however, a longer duration of follow-up will provide a more definite safety profile.