Germline BRCA testing in routine clinical practice: a single-center experience

The identification of gBRCA1/2 mutations in breast cancer patients is crucial. Successful identification of the mutations has the potential to alter disease treatment and healthcare management of patients whose relatives harbor pathogenic/likely pathogenic (P/LP) variants. In this retrospective analysis, patient- and disease-specific medical data were analyzed in a cohort of breast cancer patients with a known gBRCA1/2 status who were treated between 2019-2021. The prevalence and type of gBRCA1/2 P/LP variants, and their relation to the histopathological data of the cancers, were studied. The presence of one or more clinical criteria leading to germline testing, the outcome of patient management, and family member outcomes were collected. Germline variants were found in 67/259 cases and included 61 P/LP alterations and six "variants of unknown significance" (VUS) of the BRCA1/2 genes. A spectrum of 31 different variants was detected; eight of them occurred in more than one patient, of which three (detected in 26 cases) belonged to the mutations most prevalently detected by the previously used technology in Hungary. The likelihood of revealing a pathogenic gBRCA1/2 mutation increased with the number of risk criteria for germline testing. The presence of three or more risk criteria was predictive for carrying a gBRCA1/2 mutation with an odds ratio (OR) of 10.65 (95% CI 5.20-21.80, p < 0.001). Among the histopathology data, a higher rate of grade 3 or triple negative breast cancer was found among gBRCA1/2 P/LP variant carriers as compared to that in non-carriers. For ultimately revealing a gBRCA1/2 P/LP variant, a positive family history (OR 6.69, 95% CI 1.82-24.64, p = 0.003) and triple negative breast cancer (OR 5.65, 95% CI 2.73-11.71, p < 0.001) were the strongest independent predictive factors. Knowing of gBRCA1/2 alterations meant healthcare management was modified in 86.9% of cases. Germline testing for breast cancer patients, guided by current protocols, is essential for optimizing patient care. Adhering to established clinical criteria facilitates effective patient selection while preventing the unnecessary expansion of testing to average-risk populations. Keywords: BRCA1/2, breast cancer, cancer susceptibility genes, germline testing, medical genetics.