Oncologic Outcomes by Pathogenic Mutation Status in Young Luminal Breast Cancer: A Propensity-Matched Cohort.

[PURPOSE] Young patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors often exhibit poor outcomes. This study evaluated whether mutation contributes to prognosis by comparing oncologic outcomes according to status.

[MATERIALS AND METHODS] 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 testing, 967 patients were included (excluding low ER expression). Ninety-eight patients (10.1%) were mutation carriers. Propensity score matching (1:4) and multivariate Cox regression were performed using covariates differing between groups.

[RESULTS] mutation carriers showed more aggressive features. They had worse distant metastasis-free survival (DMFS) compared with noncarriers (hazard ratio [HR], 2.40, < .001), with a greater risk in late DMFS beyond 5 years (HR, 3.50, < .001). These findings persisted after adjustment (DMFS HR, 1.76, = .038, late DMFS HR, 2.84, = .009). Overall survival was not significantly different. Bone was the most common first site of metastasis in carriers, whereas noncarriers more frequently showed metastasis to multiple sites. In exploratory subgroup analysis, luminal A-like carriers consistently showed the poorest survival among the four subgroups.

[CONCLUSION] In luminal-type YBC excluding low ER expression, 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.