Comparing Prognosis for BRCA1, BRCA2, and Non-BRCA Breast Cancer

Area of Science:

• Oncology
• Genetics
• Epidemiology

Background:

• Germline pathogenic variants (PV) in BRCA1 and BRCA2 genes are linked to Hereditary Breast/Ovarian Cancer Syndrome, accounting for 20% of familial breast cancer (BC).
• Previous studies on BRCA1/2 and BC outcomes have shown conflicting results, often with a higher proportion of BRCA1 BC patients.
• In Portugal, BRCA2 BC is more prevalent than BRCA1 BC, necessitating population-specific outcome analyses.

Purpose of the Study:

• To compare clinicopathological characteristics and prognosis between BC patients with BRCA1 and BRCA2 mutations and a control group without germline PV (BRCA-wt).
• To investigate the frequency and impact of risk-reducing surgeries in BRCA-mutated BC patients.

Main Methods:

• Prospective follow-up of BC patients with diagnosed BRCA1/2 PV.
• A matched control group of BC patients without germline PV (BRCA-wt) was established based on age, decade, and stage at diagnosis.
• Comparison of overall survival (OS) and invasive disease-free survival (iDFS) across the three groups, and analysis of risk-reducing surgery outcomes in the BRCA cohort.

Main Results:

• BRCA-wt patients exhibited significantly longer time to recurrence and OS compared to BRCA-mutated patients (mean follow-up: 113.0 months).
• Among BRCA-mutated patients, no significant differences in outcomes were observed between BRCA1 and BRCA2, though BRCA2 BC patients trended towards longer iDFS and OS.
• Risk-reducing surgeries, including contralateral prophylactic mastectomy and salpingo-oophorectomy, were identified as negative predictors of invasive disease and death, respectively.

Conclusions:

• BRCA PV positivity is associated with an elevated risk of relapse and mortality in Portuguese BC patients.
• Risk-reducing mastectomy and salpingo-oophorectomy demonstrated a significant association with reduced relapse incidence and improved median iDFS and OS.