Loading
6 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Some triple-negative breast cancers arise because a person was born with a faulty BRCA1 or BRCA2 gene. This group is diagnosed younger, is found by a blood test NICE recommends for all women under 50 with triple-negative disease, and has options of its own: platinum chemotherapy works well, a year of olaparib lowers relapse, and surgery decisions weigh the risk of a second cancer.
BRCA1-associated breast cancers are mostly basal-like and triple-negative, high grade and often with a medullary pattern; BRCA2-associated cancers are mostly ER-positive, and the triple-negative share falls with age at diagnosis in BRCA1 carriers but rises in BRCA2 carriers (Mavaddat 2012; Atchley 2008). Among 1,824 triple-negative patients unselected for family history, 14.6 percent carried a deleterious germline mutation: BRCA1 8.5 percent, BRCA2 2.7 percent, PALB2 1.2 percent, and BARD1, RAD51D, RAD51C and BRIP1 0.3 to 0.5 percent each; carriers were younger and had higher-grade tumours, and the authors concluded that all triple-negative patients should be considered for BRCA testing regardless of age or family history (Couch 2015). A prospective US registry found 15.4 percent BRCA1 or BRCA2 carriers, 27.6 percent among those diagnosed at 50 or under 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); in the UK POSH cohort of 2,733 women diagnosed at 40 or under, 12 percent carried a BRCA mutation (Copson 2018). PALB2 carries a relative risk of 7.18 for breast cancer and a 53 percent risk to age 80 (Yang 2020). Outcome: in POSH, BRCA carriers with triple-negative disease had better overall survival than non-carriers at two years (95 against 91 percent, hazard ratio 0.59) but not at five (81 against 74 percent) or ten years (72 against 69 percent), and the authors advise that decisions on further risk-reducing surgery take the prognosis of the first cancer into account (Copson 2018). Treatment specifics are on the parent and early-disease pages: germline testing under NICE NG101 1.3.6 and CG164; the OlympiA year of adjuvant olaparib for high-risk HER2-negative early disease after chemotherapy, recommended by NICE TA886; olaparib and talazoparib for metastatic disease (OlympiAD, EMBRACA); and the HRD biology that predicts platinum response, on the glossary term. Somatic BRCA mutations and germline PALB2 mutations also predicted olaparib response in TBCRC 048 (Tung 2020). Contralateral risk-reducing mastectomy lowered contralateral breast cancer incidence (relative risk 0.072) and all-cause mortality (hazard ratio 0.512) in carriers with breast cancer in a meta-analysis (Li 2016), and tamoxifen after the first cancer was associated with fewer contralateral cancers in carriers regardless of ER status (Phillips 2013).
| Setting | Approach | Guideline |
|---|---|---|
| At diagnosis | Germline BRCA1 and BRCA2 testing for women under 50 with triple-negative disease including those with no family history (NICE NG101 1.3.6); UK mainstream criteria cover all triple-negative disease under 60; genetic counselling and cascade testing of relatives. | not mapped |
| Early disease after chemotherapy | One year of adjuvant olaparib for germline BRCA-mutated HER2-negative high-risk early breast cancer (OlympiA; NICE TA886); the same neoadjuvant platinum, taxane and anthracycline regimen as other triple-negative disease (NG101 1.8). | not mapped |
| Metastatic disease | Olaparib or talazoparib (OlympiAD, EMBRACA); platinum chemotherapy; PD-L1 and TROP2 ADC options as for other triple-negative disease. | not mapped |
| Surgery and the other breast | Contralateral risk-reducing mastectomy lowers contralateral cancer incidence and all-cause mortality in carriers with breast cancer (meta-analysis); the decision weighs the prognosis of the first cancer and personal preference (POSH authors; NICE CG164 counselling steps). | not mapped |