Abstract PS1-09-21: Outcomes of Immunotherapy in BRCA-Mutation Positive, Hormone-Receptor Positive, Breast Cancer: A Systematic Review

Abstract Introduction: BRCA 1 and BRCA 2 are tumor suppressor genes, and mutations in these genes occur frequently in breast cancer (BC). BRCA-mutated (BRCA-m) cancers are often high grade, poorly differentiated, and can carry worse overall survival (OS). Immunotherapy in BC is currently mainly limited to triple-negative breast cancer, but several ongoing trials are investigating immunotherapy in BRCA-m, hormone-receptor-positive (HR+) breast cancer. We aim to explore the outcomes of these trials in this study. Methods: Following PRISMA guidelines, a comprehensive search of PubMed, Cochrane, Embase, Google Scholar, and ClinicalTrials.gov (inception to May 2025) was conducted using MeSH terms for "Hormone Receptor Positive", “BRCA Mutated”, and "Immunotherapy.” After screening and excluding review articles, meta-analyses, studies without a patient population of interest, and those without relevant clinical outcomes, two studies were selected for inclusion and described systematically. Results: A total of two Phase II studies, involving 34 patients, were included in this systematic review. Mayer et al treated 18 patients with a combination of Niraparib and Dostarlimab in the neoadjuvant setting. The median age was 41.8 years. All patients were HR+, 72% (n = 13) were positive for a germline mutation in BRCA2 (gBRCA2), and 28% were positive for a mutation in gBRCA1. The percentages of patients with stages I, II, and III were 38.9%, 44.5%, and 16.7%, respectively. At the time of surgery, 19% (n = 3/16) had a pathological complete response (pCR), and 69% (11/16) had residual disease. The mean absolute increase in stromal tumor infiltrating lymphocytes (sTILs) in 12 evaluable patients was 11.9%. Commonly reported adverse events included rash (25.0%), elevated liver function tests (18.8%), diarrhea (12.5%), and hypertension (12.5%). Cortesi et al reported outcomes of Pembrolizumab and Carboplatin combination in 16 patients with gBRCA-m, HR+ m metastatic breast cancer. All patients were females with a median age of 50 years (range, 34-69 years), and the liver was the most common site of metastasis (n = 10, 62%). 38% (n = 6/16) had no prior treatment, 70% (n = 7/10) had previously received hormone therapy (HT), and 40% (n = 4/10) had received a combination of HT and CDK4/6 inhibitors. The overall response rate (ORR) was 47% (n = 7/15) with a disease control rate (DCR) of 87% (n = 13/15). DCR was 100% in patients in the first-line setting (n = 12). All patients reported treatment-emergent adverse events (TEAEs),