Survival outcomes in hormone receptor-negative breast cancer among BRCA carriers versus noncarriers in western Sweden.

Abstract

Background and purpose: BRCA-related hormone receptor (HR)-negative breast cancers (BC) are reported to have aggressive tumor biology but also exhibit chemosensitivity. However, the impact of BRCA1/2 pathogenetic variants (PV) on BC outcomes remains unclear. This study compares survival outcomes for HR-negative BC between BRCA carriers and noncarriers.

Patients/material and methods: From 489 female BRCA-carriers prospectively registered in western Sweden (1996-2017), those with primary HR-negative BC who underwent breast surgery until 2019 were included in the BRCA cohort. For each BRCA-carrier, three BRCA-noncarriers with HR-negative BC were matched based on age, time of diagnosis, and follow-up duration. Overall survival (OS) was analyzed using Kaplan‑Meier estimates and Cox proportional hazard ratios after adjustment for stage, chemotherapy, and surgical technique. A sensitivity analysis was performed to investigate the effect of HER2 status on HR-negative BC diagnosed after 2007.

Results: Among the 106 BRCA carriers, 101 (95%) had a BRCA1 and 5 (5%) a BRCA2 PV. Most of the BRCA-carriers (89/106, 84%) were diagnosed with BC prior to genetic screening. Surgical techniques were similar between BRCA-carriers (n = 106) and noncarriers (n = 318). Chemotherapy was more common among BRCA-carriers (87% vs. 72%, p < 0.001). No significant difference in OS was found between BRCA-carriers and noncarriers among patients with HR-negative BC (adjusted HR: 0.81 [95% confidence interval [CI]: 0.43-1.53], p = 0.51) or considering HER2 status (adjusted HR 0.95 [95% CI: 0.43-2.07], p = 0.89).

Interpretation: This study suggests that BRCA1/2 pathogenic variants do not independently impact survival outcomes in HR-negative BC. However, a moderate association between BRCA status and OS cannot be ruled out.