Long-term safety of controlled ovarian stimulation for fertility preservation before chemotherapy treatment in patients with breast cancer

Objective: To evaluate the long-term safety of controlled ovarian stimulation for fertility preservation before breast cancer chemotherapy treatment. Design: Retrospective observational cohort. Subjects: Two hundred thirteen women aged 18 to 43 years with newly diagnosed stage I–III breast cancer treated with systemic chemotherapy during 2015–2019. Of those, 74 underwent controlled ovarian stimulation for fertility preservation recipients, and 141 did not (controls). Exposure: controlled ovarian stimulation for fertility preservation. Main Outcome Measures: Invasive disease-free survival, calculated from the time of surgery to the time of detection of breast cancer recurrence or death, whichever came first. Results: At diagnosis, fertility preservation recipients were significantly younger than controls (32.7 vs. 38.5 years), were less likely to be partnered (44.4% vs. 90.1%) or parous (38.9% vs. 95%), and were more likely to harbor a BRCA germline mutation (36.5% vs. 14.2%). Disease characteristics and treatment modalities were comparable between groups, apart from tumor staging, with maximal tumor diameter being >5 cm in 22.2% of fertility preservation recipients as opposed to 5.7% of controls. Mean follow-up was 60.9 and 65.4 months for fertility preservation recipients and controls, respectively. Five-year invasive disease-free survival was 80% for fertility preservation recipients and 86% for controls. In a multivariate analysis adjusted for statistically significant covariates, invasive disease-free survival remained similar between the groups (hazards ratio [HR], 0.86; 95% confidence interval [CI], 0.4–1.87). Invasive disease-free survival rates were not statistically different in clinically relevant subgroups, including patients receiving neoadjuvant chemotherapy (HR, 1.57; 95% CI, 0.62–3.99) and those cotreated with tamoxifen during stimulation because of an estrogen receptor positive disease (HR, 1.66; 95% CI, 0.67–3.49). Conclusion: Fertility preservation with controlled ovarian stimulation for patients with breast cancer was not found to impair long-term oncologic outcomes, including in emergent clinically relevant subgroups.