Survival, fertility preservation, and pregnancy after treatment in young patients with BRCA-associated triple-negative breast cancer.

Abstract

e23345 Background: As survival outcomes improve with novel systemic therapies, fertility preservation (FP) and post-treatment pregnancy have become increasingly important issues for young patients with triple-negative breast cancer (yTNBC) harboring BRCA1/2 pathogenic variants. However, real-world data on reproductive outcomes and survivorship issues in this population remain limited. Methods: We retrospectively analyzed patients younger than 40 years with yTNBC and confirmed germline BRCA1/2 pathogenic variants who underwent primary surgery between 2007 and 2022 at a single tertiary cancer center. Oncologic outcomes, FP practices, pregnancy outcomes, and the timing of risk-reducing salpingo-oophorectomy (RRSO) were evaluated. Results: Thirty-eight patients were included. The median age at surgery was 34 years. BRCA1 and BRCA2 pathogenic variants were identified in 80% and 20% of patients, respectively, and 65% had stage II disease. Chemotherapy was administered to 97.4% of patients, including neoadjuvant chemotherapy (53.8%), adjuvant capecitabine (7.9%), and PARP inhibitors (13.2%). With a median follow-up of 5.9 years, disease events included lung metastases (n=2), local recurrence (n=1), ipsilateral breast tumor recurrence (n=2), contralateral breast cancer (n=10), ovarian cancer (n=2), and ureteral cancer (n=1). The 5- and 10-year overall survival rates were 97.4% and 87.6%, respectively. Among 12 patients expressing a desire for future pregnancy, 7 attempted FP, and FP was successfully completed in 6 patients prior to chemotherapy. All patients received genetic counseling and underwent surveillance for breast and ovarian cancer at 6- and 3-month intervals, respectively. Six patients achieved a total of 11 pregnancies, including one ongoing pregnancy, resulting in 6 live births. All pregnancies occurred in patients without disease recurrence. Notably, three of the six patients who achieved pregnancy had a prior history of treatment with PARP inhibitors. The median interval from surgery to first pregnancy was 2.5 years. RRSO was performed in 13 patients at a median age of 41 years, with a median interval of 3.0 years from surgery. Conclusions: Despite the limited sample size, this study provides real-world insight into survivorship and reproductive outcomes in young patients with BRCA-associated yTNBC. Favorable survival and successful pregnancies were observed following individualized, multidisciplinary care. Importantly, these findings highlight the emerging and largely unexplored issue of pregnancy following PARP inhibitor exposure. The high incidence of contralateral breast cancer and variability in RRSO timing underscore the need for personalized survivorship planning integrating cancer risk management with reproductive decision-making in the era of novel systemic therapies.