Collaborator: Albert Einstein College of Medicine
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Reduced risk BRCA1 and BRCA2 variants: Insight into classification of concordant variants between two commercial laboratories
The identification and reporting of reduced risk BRCA1 and BRCA2 (RR-BRCA) variants is complex and poses challenges for patient counseling. We sought to compile and compare data for RR-BRCA variants reported by two clinical diagnostic laboratories.
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Mutation prevalence tables for hereditary cancer derived from multi-gene panel testing
Abstract Multigene panel testing for cancer predisposition mutations is becoming routine in clinical care. However, the gene content of panels offered by testing laboratories vary significantly, and data on mutation detection rates by gene and by the panel is limited, causing confusion among clinicians on which test to order. Using results from 147,994 multigene panel…
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The Contribution of Germline Predisposition Gene Mutations to Clinical Subtypes of Invasive Breast Cancer From a Clinical Genetic Testing Cohort
Abstract Background The germline cancer predisposition genes associated with increased risk of each clinical subtype of breast cancer, defined by estrogen receptor (ER), progesterone receptor (PR), and HER2, are not well defined. Methods A total of 54 555 invasive breast cancer patients with 56 480 breast tumors were subjected to clinical hereditary cancer multigene panel testing.…
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Rare BRIP1 missense alleles confer risk for ovarian and breast cancer.
Abstract Germline loss-of-function mutations in BRCA1 interacting protein C-terminal helicase 1 (BRIP1) are associated with ovarian carcinoma and may also contribute to breast cancer risk, particularly among patients who develop disease at an early age. Normal BRIP1 activity is required for DNA interstrand cross-link (ICL) repair and is thus central to the maintenance of genome…
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A clinical guide to hereditary cancer panel testing: evaluation of gene-specific cancer associations and sensitivity of genetic testing criteria in a cohort of 165,000 high-risk patients
Abstract Purpose Despite the rapid uptake of multigene panel testing (MGPT) for hereditary cancer predisposition, there is limited guidance surrounding indications for testing and genes to include. Methods To inform the clinical approach to hereditary cancer MGPT, we comprehensively evaluated 32 cancer predisposition genes by assessing phenotype-specific pathogenic variant (PV) frequencies, cancer risk associations, and…
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Genetic predisposition to invasive lobular carcinoma
Despite accounting for about 15% of all BCs diagnosed each year, making ILC the second most common histologic subtype after invasive ductal breast cancer (IDC), it is largely underrepresented in genetic studies. Pathogenic alteration frequencies were compared between female ILC and IDC cases, among ~91,000 patients referred for testing, including ~4700 ILC cases Pathogenic alterations…