Gene-Specific Outcomes After Central Nervous System Metastases in Germline BRCA1- and BRCA2-Associated Breast Cancer

Decaminada, A; Sunder-Plassmann, R; Ho, WK; Muhr, D; Starzer, AM; Berghoff, AS; Bartsch, R; Singer, CF; kConFab Investigators; Tan, YY

Author(s): Decaminada, A; Sunder-Plassmann, R; Ho, WK; Muhr, D; Starzer, AM; Berghoff, AS; Bartsch, R; Singer, CF; kConFab Investigators; Tan, YY;
Details: Publication Year 2026-04-14,Volume 18,Issue #8,Page 1240
Journal Title: Cancers
Publication Type: Research article
Abstract: Background: Many studies evaluating central nervous system (CNS) metastases in breast cancer (BC) combine germline BRCA1 and BRCA2 pathogenic variant carriers, limiting gene-specific interpretation. We evaluated gene-specific overall survival (OS) after CNS metastasis and time to CNS involvement. Methods: We retrospectively identified BC patients with confirmed CNS metastases (1995-2022) from the Medical University of Vienna and the kConFab consortium. Germline status was classified as gBRCA1 PV, gBRCA2 PV, or non-carrier. Primary endpoint was OS from CNS metastasis diagnosis; secondary endpoint was CNS metastasis-free interval from primary BC diagnosis. Kaplan-Meier/log-rank tests were used for group comparisons. Multivariable Cox models assessed OS in complete cases, stratified by molecular subtype and adjusted for prognostic factors. Sensitivity analyses included subtype-adjusted and time-period models. Results: Among 115 patients (gBRCA1 n = 32, gBRCA2 n = 18, and non-carriers n = 65), median OS differed by germline status (p = 0.019): 20.0 months (95% CI 6.7-60.0) for gBRCA2 versus 7.1 months (95% CI 3.7-10.0) for gBRCA1 and 7.6 months (95% CI 3.4-12.0) for non-carriers. In subtype-stratified analyses, gBRCA1 showed similar mortality to non-carriers (HR 0.90, 95% CI 0.49-1.64, p = 0.730), while gBRCA2 showed a lower but non-significant hazard (HR 0.48, 95% CI 0.18-1.25, p = 0.131). Median CNS metastasis-free interval was longer for gBRCA2 (8.4 years) versus gBRCA1 (3.0 years) and non-carriers (3.1 years; p = 0.020). Sensitivity analyses were consistent. Conclusions: gBRCA2 carriers demonstrated longer unadjusted OS after CNS metastasis and a longer CNS metastasis-free interval compared with gBRCA1 carriers and non-carriers. However, these associations were attenuated and not statistically significant after adjustment, and should therefore be interpreted as hypothesis-generating. These findings supports further investigation of gene-specific CNS disease trajectories in larger cohorts.
Publisher: MDPI
Keywords: Brca1; Brca2; CNS metastasis; brain metastasis; breast cancer; overall survival
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.3390/cancers18081240
Open Access at Publisher's Site: https://doi.org/10.3390/cancers18081240
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-05-14 12:09:38

Last Modified: 2026-05-14 12:09:50