{"entity":{"id":"paper-couch-tnbc-germline-17-genes-jco-2015","kind":"paper","name":"Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer","aka":[],"tldr":"Testing 1,824 women with triple-negative breast cancer regardless of family history found an inherited cancer-gene mutation in one in seven: BRCA1 in 8.5%, BRCA2 in 2.7% and other repair genes in 3.7%, which is why every TNBC patient is now offered germline testing.","summary":"1,824 TNBC patients unselected for family history of breast or ovarian cancer were recruited through 12 studies and germline DNA sequenced for 17 predisposition genes. Deleterious mutations were identified in 14.6%: 11.2% in BRCA1 (8.5%) and BRCA2 (2.7%), and 3.7% in 15 other genes, mostly homologous recombination genes including PALB2 (1.2%) and BARD1, RAD51D, RAD51C and BRIP1 (0.3% to 0.5%). Carriers were diagnosed younger (P less than .001) with higher-grade tumours (P .01).","asOf":"2026-09-24","links":[{"label":"Couch et al., J Clin Oncol 2015: germline mutations in 17 genes among 1,824 unselected TNBC patients","url":"https://doi.org/10.1200/JCO.2014.57.1414"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25452441/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["germline-testing"],"targets":["brca","palb2","bard1","rad51c","rad51d"],"drugs":[],"companies":[],"institutions":["mayo-clinic"],"pathways":[],"terms":["gbrca-mutation","germline-vs-somatic"],"trials":[],"people":["priyanka-sharma"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/JCO.2014.57.1414","pmid":"25452441","authors":"Couch FJ, Hart SN, Sharma P, et al.","paperType":"observational","findings":["Deleterious germline mutation in 14.6%: BRCA1 8.5%, BRCA2 2.7%, other genes 3.7%.","PALB2 1.2%; BARD1, RAD51D, RAD51C and BRIP1 0.3% to 0.5% each.","Carriers were younger with higher-grade tumours."],"whatItMeans":"This cohort underpins the guideline shift to germline BRCA1/2 testing for all TNBC patients regardless of age or family history, and it is the prevalence figure the corpus uses for germline BRCA1 in TNBC.","caveats":["Predominantly European-ancestry research cohorts.","Risk estimates for the non-BRCA genes were judged too imprecise for relatives' counselling at the time."],"changedPractice":true,"participants":1824},"route":"/key-papers/paper-couch-tnbc-germline-17-genes-jco-2015/","neighbours":{"cancer":[{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"}],"target":[{"id":"bard1","kind":"target","name":"BARD1","route":"/targets/bard1/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"palb2","kind":"target","name":"PALB2","route":"/targets/palb2/"},{"id":"rad51c","kind":"target","name":"RAD51C","route":"/targets/rad51c/"},{"id":"rad51d","kind":"target","name":"RAD51D","route":"/targets/rad51d/"}],"institution":[{"id":"mayo-clinic","kind":"institution","name":"Mayo Clinic","route":"/institutions/mayo-clinic/"}],"term":[{"id":"gbrca-mutation","kind":"term","name":"Germline BRCA mutation (gBRCA)","route":"/terms/gbrca-mutation/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"}],"person":[{"id":"priyanka-sharma","kind":"person","name":"Priyanka Sharma","route":"/people/priyanka-sharma/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}],"drug":[{"id":"bracanalysis-cdx","kind":"drug","name":"BRACAnalysis CDx","route":"/drugs/bracanalysis-cdx/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"},{"id":"talazoparib","kind":"drug","name":"Talazoparib","route":"/drugs/talazoparib/"}],"biomarker":[{"id":"brca-germline","kind":"biomarker","name":"Germline BRCA1/2 pathogenic variant (gBRCAm)","route":"/biomarkers/brca-germline/"}]}}