Objective: The aim of this study is to evaluate the clinicopathological features and prognostic impact of breast cancer harboring germline BRCA1/2 mutation.

Materials and Methods: This cross-sectional study was conducted on early and de novo metastatic BRCA mutant female breast cancer patients diagnosed at King Salman Medical City, Medina region, Kingdom Saudi Arabia (KSA), since 2022. A germline BRCA1/2 mutation was confirmed from blood samples by a next-generation sequencing test.

Results: Median age of diagnosis was 35 years old (35-60), and family history of breast cancer was present in 33.3%. Sixty-six percent of patients were in an early stage; however, 34% of patients had de novo metastatic diseases; 22.2% of them had central nervous system (CNS) involvement. On follow-up of early breast cancer patients, 30% developed contralateral breast cancers, 21% developed ipsilateral disease, while 57% developed distant metastasis. Triple-Negative Breast Cancer (TNBC) was found in 45% of these BRCA1/2 mutant breast cancer patients, which was more prevalent in BRCA1 carriers accounting for 75% of cases. No differences were found in the toxicity due to breast radiation between BRCA1 and BRCA2 patients regarding skin dermatitis, pigmentation, breast or chest wall oedema, and telangiectasia. Most of the de novo metastatic patients were BRCA2 mutant vs. BRCA1 (66.5% vs. 33.5%). Median progression-free survival (PFS) of all BRCA-mutated patients was 13 months. However, BRCA1 patients showed longer PFS (median; 20 vs. 12 months, p=0.4). Median overall survival (OS) of all BRCA mutants was 23 months, with better OS in BRCA1 mutant patients (median OS: 25 vs. 19 months, p=0.3).

Conclusions: To our knowledge, this is the first cross sectional study investigating the clinical and prognostic value of germline BRCA1/2 mutation in breast cancer in our locality. Germline BRCA1/2 carriers presented with more aggressive disease and poor outcomes. Germline BRCA2 mutant patients were more often diagnosed at an advanced stage and showed poorer PFS and OS compared to their BRCA1 mutation carriers counterparts.