Abstract
IntroductionBreast cancer patients with germline pathogenic variants may benefit from risk-reducing surgeries, intensive screening, and targeted cancer therapies. There is a paucity of data regarding prevalence and distribution of germline pathogenic variants in the Brazilian population. Our primary endpoint was the description of prevalence and distribution of germline pathogenic variants among breast cancer patients who underwent next-generation sequencing (NGS) panel testing. Secondary endpoint was the assessment of predictive factors of a positive test.MethodsWe analyzed NGS results, personal, and family history data from a prospectively collected cohort of breast cancer patients from August 2013 to May 2019. Exact logistic regression was used to perform multivariable analysis.ResultsOf 370 breast cancer patients, we found 59 pathogenic variants in 57 (15%) patients. Pathogenic variants were identified in BRCA1 (24%), ATM (14%), BRCA2 (10%), TP53 (8%), PALB2 (8%), CHEK2 (7%), CDH1 (3%), RAD51C (3%), MITF (2%), PMS2 (2%), RAD51D (2%), and TERT (2%). Monoallelic MUTYH pathogenic variants were found in 15%. After multivariable analysis, age of diagnosis (OR 0.89, 95% CI: 0.81–0.95, for each year increase), triple-negative subtype (OR 17.2, 95% CI: 3.74–114.72), and number of breast cancers in the family (OR 2.46, 95% CI 1.57–4.03, for each additional case) were associated with BRCA1 pathogenic variants. In the present study, a quarter of triple-negative breast cancer patients harbored a germline pathogenic variant and two-thirds of those were BRCA1 carriers.ConclusionsPrevalence and distribution of germline pathogenic variants in this Brazilian sample of breast cancer patients are mostly similar to other populations. However, there is a trend to an overrepresentation of TP53 pathogenic variants that merits confirmation in further studies. Early-onset breast cancer patients should be offered genetic counseling, particularly those with triple-negative subtype.
Highlights
Breast cancer patients with germline pathogenic variants may benefit from risk-reducing surgeries, intensive screening, and targeted cancer therapies
Other high penetrance genes such as TP53 and PALB2 have been described as breast cancer susceptibility genes, as well as moderate penetrance genes such as ATM and CHEK2 (5)
Recommendations for BRCA1 and BRCA2 range from riskreducing mastectomies (6) to intensive screening with breast magnetic resonance imaging (MRI) (7) and specific therapies such as platinum agents (8) and PARP inhibitors (9, 10)
Summary
Breast cancer patients with germline pathogenic variants may benefit from risk-reducing surgeries, intensive screening, and targeted cancer therapies. There is a paucity of data regarding prevalence and distribution of germline pathogenic variants in the Brazilian population. Our primary endpoint was the description of prevalence and distribution of germline pathogenic variants among breast cancer patients who underwent next-generation sequencing (NGS) panel testing. 10% of breast cancer patients carry a germline pathogenic variant that may indicate screening strategies or preventive recommendations (2). There is an ongoing effort to understand the magnitude and the modifying factors of risk conferred by each gene and to which extent we could generalize what we learned from high penetrance genes to moderate penetrance counterparts (11)
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