Oncologic Outcomes by Pathogenic <i>BRCA</i> Mutation Status in Young Luminal Breast Cancer: A Propensity-Matched Cohort.

Abstract

Young patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors often exhibit poor outcomes. This study evaluated whether <i>BRCA</i> mutation contributes to prognosis by comparing oncologic outcomes according to <i>BRCA</i> status. We conducted a retrospective study of a prospective institutional cohort. Among 1,025 patients 40 years and younger with ER-positive, HER2-negative breast cancer who underwent <i>BRCA1/2</i> testing, 967 patients were included (excluding low ER expression). Ninety-eight patients (10.1%) were <i>BRCA</i> mutation carriers. Propensity score matching (1:4) and multivariate Cox regression were performed using covariates differing between groups. <i>BRCA</i> mutation carriers showed more aggressive features. They had worse distant metastasis-free survival (DMFS) compared with noncarriers (hazard ratio [HR], 2.40, <i>P</i> < .001), with a greater risk in late DMFS beyond 5 years (HR, 3.50, <i>P</i> < .001). These findings persisted after adjustment (DMFS HR, 1.76, <i>P</i> = .038, late DMFS HR, 2.84, <i>P</i> = .009). Overall survival was not significantly different. Bone was the most common first site of metastasis in <i>BRCA</i> carriers, whereas noncarriers more frequently showed metastasis to multiple sites. In exploratory subgroup analysis, luminal A-like <i>BRCA</i> carriers consistently showed the poorest survival among the four subgroups. In luminal-type YBC excluding low ER expression, <i>BRCA</i> carriers demonstrated more aggressive features and significantly worse distant metastasis outcomes. These findings support the need for long-term surveillance and consideration of tailored treatment strategies, including PARP inhibitors, in this high-risk population.