MBC is a rare entity accounting for less than 1% of all breast cancer (BC), with a lack of reliable data in this specific subset.
FH, CP characteristics, OG testing results on constitutional pathogenic variants (PV) in known BC predisposition genes were retrospectively collected in all MBC patients (pts) who had an OG consultation at Oscar Lambret Center, Lille, France between 2000 and 2021. Outcomes were overall survival (OS) and event-free survival (EFS), defined as time from first diagnosis to first recurrence or death from any cause. Key patient data, Kaplan-Meier plots and outcomes were described by PV status.
Out of the 98 MBC pts included: 10 (10.2%) tested positive for a PV (6 BRCA2, 3 BRCA1, and 1 BRCA2 and RAD51C). Groups were similar regarding age (67.6 vs 61.8 years; p = 0.08), BMI, subtype or TNM stage. Although statistically not significant, PV carriers had more aggressive primary tumors (histological grade III 44.4% vs 20.7%; p = 0.2) and Ki67 levels (40% vs 23%; p = 0.3). Treatment strategies were similar. First degree FH of BC was more frequent in PV carriers (7/10 vs 26/88; p=0.03), but no differences in FH of ovarian, prostate, pancreatic cancer or melanoma were noted. One patient had FH of MBC (BRCA2 PV carrier). The median follow-up was 4.7 years (IQR 0.5-19.1). Overall, 13 deaths were reported and 13 pts were alive with breast cancer recurrence. OS was 87.5% in PV non-carriers vs 88.9% in PV carriers at 10 years. EFS was 84.8% vs 77.8% at 5 years. Second cancer were more frequent in PV carriers, with 5/10 pts diagnosed (3 prostate, 1 pancreatic and 1 colorectal cancer) vs 8/88 pts in the non PV carrier group (p=0.004).
High rates of BRCA1/2 PV were found in unselected MBC pts, warranting OG testing for all MBC pts. A familial history of BC was more frequent in PV carriers. No particular CP were associated with PV carriers, even if tumors seem to be more aggressive. BC survival outcomes were comparable regardless of mutational status but occurrence of another cancer in half of MBC pts with a PV confirms the indication of specific screenings.
Centre Oscar Lambret.
Has not received any funding.
All authors have declared no conflicts of interest.