Germline BRCA testing criteria for triple-negative breast cancer (UK)

NICE NG101 (1.3.6, 2017) tells clinicians to offer genetic testing for BRCA1 and BRCA2 mutations to women under 50 years with triple-negative breast cancer, including those with no family history of breast or ovarian cancer, and points to the National Genomic Test Directory for the criteria that govern testing for NICE-recommended PARP inhibitors (R444.1). NICE CG164 sets the general framework: in secondary care and specialist clinics a carrier probability calculator with acceptable performance, such as CanRisk (BOADICEA) or the Manchester scoring system, is used; genetic testing is offered to a person with breast or ovarian cancer whose combined BRCA1 and BRCA2 carrier probability is 10 percent or more, to an affected relative at the same threshold, or to an unaffected person at 10 percent or more when no affected relative is available; fast-track testing within four weeks of diagnosis was to be offered only in a trial; every person offered testing should have a detailed consultation with a clinical geneticist or genetics counsellor; and clinicians should seek genetics advice for families containing triple-negative breast cancer under 40, Jewish ancestry, sarcoma under 45, glioma or childhood adrenal cortical carcinoma, complicated patterns of cancers at a young age or a very strong paternal history. A 2024 UK study of 1,061 women with breast cancer across three cohorts found pathogenic variants in 3.4 percent (BRCA1 9, BRCA2 18, PALB2 9); the current mainstream criteria, women diagnosed under 40, all triple-negative disease under 60, or a Manchester score of 15 or more, identified 58 percent of variants by testing 190 women (detection rate 8.4 percent, specificity 83.5 percent), a Manchester threshold of 12 raised sensitivity to 66.7 percent, no variant was found in 158 women with grade 1 cancers, and the authors argue for lowering the threshold to detect more carriers (Evans 2024). The yield in triple-negative disease justifies the special rule: 11.2 percent BRCA1/2 and 14.6 percent any predisposition gene among 1,824 unselected patients (Couch 2015); 15.4 percent BRCA1/2 in a prospective registry, 27.6 percent at 50 or under, 11.4 percent at 51 to 60 and 4.9 percent at 61 or over, with NCCN's rule of testing all triple-negative disease at 60 or under catching every carrier (Sharma 2014). A positive result opens adjuvant olaparib for high-risk early disease (NICE TA886), informs surgery, and starts cascade testing of relatives; Cancer Research UK notes that testing usually starts with the affected family member most likely to carry the change.