Abstract WP216: Breast Cancer Susceptibility Genes And Cerebral Small Vessel Disease

Abstract

Introduction: Aside from being implicated in breast and ovarian cancer, breast cancer susceptibility genes (BRCA) growing evidence suggests an additional intersection between BRCA mutations and hypercholesterolemia, endothelial damage, hyperglycemia and an increased non-neoplastic mortality. With the influence of BRCA on typical cerebrovascular risk factors, we aimed to identify if BRCA mutations increased the prevalence of cerebral small vessel disease (CSVD). Methods: We performed a retrospective cross-sectional chart review of adults with confirmed BRCA1 or BRCA2 mutations compared against BRCA wild-type individuals with breast and/or ovarian cancer. Demographic and medical history were recorded. Brain MRI was interpreted for markers of CSVD. Statistical significance (p < 0.05) was tested via the Chi-squared or Fisher’s, Wilcoxon rank-sum and the Student’s t-test analyses for binary, ordinal or interval variables, respectively. Adjusted logistic regression models were fit to calculate odds ratio. All models were tested for multicollinearity by variance inflation factor calculation and for goodness-of-fit (GOF) via the Hosmer-Lemeshow GOF test. Results: One hundred forty individuals were included, with 47% (66/140) being BRCA mutant. Demographic and cerebrovascular risk factors were similar amongst the cohort. Estrogen antagonist therapy was more common in the BRCA wild-type group [25% (16/64) vs 44.6% (33/74), p = 0.016]. Lacunar infarcts, Fazekas grading and perivascular spaces were not significantly different across the cohort. Cerebral microbleeds (CMBs) were more prevalent in those with BRCA mutation: [36.4% (24/66) vs 18.9% (14/74), p = 0.021]. This finding persisted despite adjustment for cerebrovascular risk factors (OR 2.71, 95%CI 1.20 - 6.14, p = 0.017) yielding a predicted probability of 18.2% (95%CI 3.7 - 32.8). Conclusion: For those with BRCA mutation, we identified a nearly 3 fold increase in CMB prevalence despite adjustment for cerebrovascular risk factors. The mechanism underlying is presently unknown, though likely related to endothelial dysregulation. Further studies are needed to confirm our findings on a larger scale and investigate intraparenchymal hemorrhage risk amongst those with BRCA mutations.