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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 1.3.5 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).
About one in nine triple-negative patients unselected for family history carries a germline BRCA1 (8.5 percent) or BRCA2 (2.7 percent) mutation, and one in seven a mutation in one of 17 predisposition genes (Couch 2015); from the other direction, 57.1 percent of breast cancers in BRCA1 carriers are triple-negative (Atchley 2008).
Most cancers start in the ducts and drain first to the axillary nodes, which is why the armpit is checked and a sentinel node is sampled.
Same organ: Triple-negative breast cancer (TNBC), Breast cancer (all types), HR-positive / HER2-negative breast cancer, HER2-positive breast cancer, Male breast cancer, Ductal carcinoma in situ (DCIS), High-risk early HR-positive breast cancer, HR-positive metastatic breast cancer after CDK4/6 inhibitors, HER2-low and HER2-ultralow metastatic breast cancer, Early HER2-positive breast cancer, HER2-positive breast cancer with brain metastases, Early triple-negative breast cancer, Metastatic triple-negative breast cancer, Basal-like 1 triple-negative breast cancer (BL1), Basal-like 2 triple-negative breast cancer (BL2), Mesenchymal triple-negative breast cancer (M), Mesenchymal stem-like triple-negative breast cancer (MSL), Luminal androgen receptor triple-negative breast cancer (LAR), Immunomodulatory triple-negative breast cancer (IM), Metaplastic breast carcinoma, Carcinoma with medullary pattern (medullary breast cancer), Adenoid cystic carcinoma of the breast, Apocrine carcinoma of the breast, Secretory carcinoma of the breast, Inflammatory breast cancer, Paget disease of the nipple, Phyllodes tumour of the breast, Invasive lobular carcinoma of the breast, Invasive breast carcinoma of no special type (invasive ductal carcinoma), Tubular carcinoma of the breast, Mucinous carcinoma of the breast, Papillary carcinomas of the breast (encapsulated, solid and invasive papillary), Invasive cribriform carcinoma of the breast, Invasive breast carcinoma with medullary pattern (medullary carcinoma), Invasive micropapillary carcinoma of the breast, Neuroendocrine neoplasms of the breast, Lobular carcinoma in situ (LCIS)
Germline BRCA1 and BRCA2 testing for women under 50 with triple-negative disease including those with no family history (NICE NG101 1.3.5); UK mainstream criteria cover all triple-negative disease under 60; genetic counselling and cascade testing of relatives.
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).
Olaparib or talazoparib (OlympiAD, EMBRACA); platinum chemotherapy; PD-L1 and TROP2 ADC options as for other triple-negative disease.
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).
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Query for this cancer: (TITLE:"BRCA-associated triple-negative breast cancer" OR ABSTRACT:"BRCA-associated triple-negative breast cancer" OR TITLE:"Germline BRCA1 triple-negative breast cancer" OR ABSTRACT:"Germline BRCA1 triple-negative breast cancer" OR TITLE:"gBRCA TNBC" OR ABSTRACT:"gBRCA TNBC" OR TITLE:"Hereditary triple-negative breast cancer" OR ABSTRACT:"Hereditary triple-negative breast cancer" OR TITLE:"BRCA1-related basal-like breast cancer" OR ABSTRACT:"BRCA1-related basal-like breast cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about BRCA-associated triple-negative breast cancer, not a curated reading list.
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Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Avoid grapefruit and Seville oranges.
Dose by Calvert formula using GFR (see the calculators).
200 mg twice daily for CrCl 31-50.
0.75 mg daily for CrCl 30-59; 0.5 mg for 15-29.
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