Distinct Global and Regional Brain Volume Patterns in BRCA Mutation Carriers

Document Type

Conference Proceeding

Publication Date

1-29-2026

Publication Title

Stroke

Keywords

Brain Health, Magnetic resonance, Gene mutations, Risk Factors

Abstract

Background: Germline mutations in BRCA1 and BRCA2 are well-established hereditary risk factors for breast and ovarian cancers, with lesser-known implications in prostate and pancreatic cancers. These associations reflect impaired DNA damage repair that compromises genomic stability. In animal models, BRCA1 inactivation has also been linked to apoptotic pathways during neurodevelopment, resulting in hypoplasia of key brain regions. We aimed to investigate whether such mechanisms translate to structural brain differences in human BRCA mutation carriers. Methods: We retrospectively analyzed MR brain scans of 12 individuals (6 with BRCA1 mutations and 6 with BRCA2 mutations), along with 12 age-matched breast cancer controls with wildtype BRCA. Patients with a history of prior intracranial lesions were excluded. Automated tissue segmentation and brain parcellation were performed using web-based Vol2Brain and AssemblyNet neuroimaging pipelines, with volumetric measures normalized to a healthy reference population. The small cohort warranted a descriptive analytical approach. Chi-Square and independent samples t-tests were conducted for univariable group comparisons. Results: The mean age was 58.3 years (IQR 48.24-67.0), and 92% (n = 22) were female; 83% (n = 10) of the BRCA group had a breast cancer diagnosis at the time of MRI. Chemotherapy regimens and treatment duration were comparable between groups (p = 0.18 and p = 0.38, respectively). BRCA mutation carriers showed higher white matter (WM) volumes (46.55 ± 11.07 % vs. 38.99 ± 3.53 %, p = 0.034) and lower gray matter (GM) volumes (39.16 ± 9.66% vs. 45.70 ± 3.74%, p = 0.04), with similar intracranial cavity volumes (ICV) and cerebrospinal fluid (CSF). Reduced lobar volumes were observed in the BRCA cohort, with significant findings in the parietal (p = 0.043) and temporal lobes (p = 0.047). Conclusions: Our study builds on growing evidence that carriage of BRCA mutations may exert independent effects on brain structure and morphology. Based on relationships between white matter integrity and cerebral small vessel disease, these findings underscore the need for further research into the role of BRCA mutations in stroke susceptibility and brain aging.

Volume

57

Issue

SUPPL_1

Find It @ Sladen

Share

COinS