# BRCA-associated triple-negative breast cancer

Source: https://onco.cc/cancers/brca-associated-tnbc/  
OnCo record `brca-associated-tnbc` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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).

## Fields

- Kind: Cancer
- Last checked: 2026-09-24
- Also known as: Germline BRCA1 triple-negative breast cancer; gBRCA TNBC; Hereditary triple-negative breast cancer; BRCA1-related basal-like breast cancer
- Tags: breast; tnbc; subtype-page
- Group: breast
- Burden: 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).
- Subtypes: Germline BRCA1-associated triple-negative breast cancer (basal-like, often medullary pattern, the majority); Germline BRCA2-associated triple-negative breast cancer (a minority of BRCA2 cancers, older at diagnosis); Germline PALB2-associated triple-negative breast cancer; Somatic (tumour-only) BRCA1 or BRCA2 mutation in triple-negative disease
- Biomarkers: Germline BRCA1, BRCA2 and PALB2 pathogenic variants (blood test); Tumour BRCA1 or BRCA2 mutation and HRD score (platinum and PARP inhibitor response); Age under 50 at diagnosis and family history (testing criteria)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/brca-associated-tnbc/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/brca-associated-tnbc/#overview
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/brca-associated-tnbc/#what-it-is [4 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/brca-associated-tnbc/#finding-it [3 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/brca-associated-tnbc/#treating-it [4 settings, 2 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/brca-associated-tnbc/#evidence [3 trials]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/brca-associated-tnbc/#science [2 targets, 1 pathway]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/brca-associated-tnbc/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/brca-associated-tnbc/#living-with-it [14 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/brca-associated-tnbc/coming/ [3 medicines]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/brca-associated-tnbc/data/ [27 connected records]

## Standard of care

- 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. ([Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Germline BRCA testing criteria for triple-negative breast cancer (UK)](https://onco.cc/terms/germline-brca-testing-criteria-tnbc/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/))
- 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). ([Olaparib](https://onco.cc/drugs/olaparib/), [OlympiA](https://onco.cc/trials/olympia/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/), [Carboplatin](https://onco.cc/drugs/carboplatin/))
- Metastatic disease: Olaparib or talazoparib (OlympiAD, EMBRACA); platinum chemotherapy; PD-L1 and TROP2 ADC options as for other triple-negative disease. ([Olaparib](https://onco.cc/drugs/olaparib/), [Talazoparib](https://onco.cc/drugs/talazoparib/), [OlympiAD](https://onco.cc/trials/olympiad/), [EMBRACA](https://onco.cc/trials/embraca/), [Platinum agents](https://onco.cc/technologies/platinum/))
- 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). ([Mastectomy](https://onco.cc/terms/mastectomy/), [Risk-reducing surgery for BRCA carriers (bilateral and contralateral mastectomy, salpingo-oophorectomy)](https://onco.cc/terms/risk-reducing-surgery-brca-carriers/))

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/BRCA_mutation
- Couch, J Clin Oncol 2015: inherited mutations in 17 genes among 1,824 triple-negative breast cancers unselected for family history: https://doi.org/10.1200/jco.2014.57.1414
- Sharma, Breast Cancer Res Treat 2014: germline BRCA mutations in a prospective triple-negative breast cancer registry: https://doi.org/10.1007/s10549-014-2980-0
- Atchley, J Clin Oncol 2008: clinical and pathological characteristics of BRCA-positive and BRCA-negative breast cancer: https://doi.org/10.1200/jco.2008.16.6231
- Mavaddat, Cancer Epidemiol Biomarkers Prev 2012: pathology of breast cancers in BRCA1 and BRCA2 carriers (CIMBA): https://doi.org/10.1158/1055-9965.epi-11-0775
- Copson, Lancet Oncol 2018: germline BRCA mutation and outcome in young-onset breast cancer (POSH): https://doi.org/10.1016/s1470-2045(17)30891-4
- Yang, J Clin Oncol 2020: cancer risks with germline PALB2 pathogenic variants, 524 families: https://doi.org/10.1200/jco.19.01907
- Tung, J Clin Oncol 2020: TBCRC 048, olaparib for metastatic breast cancer with germline PALB2 or somatic BRCA mutations: https://doi.org/10.1200/jco.20.02151
- Li, Clin Cancer Res 2016: effectiveness of prophylactic surgeries in BRCA1 or BRCA2 carriers, meta-analysis: https://doi.org/10.1158/1078-0432.ccr-15-1465
- Phillips, J Clin Oncol 2013: tamoxifen and contralateral breast cancer risk in BRCA1 and BRCA2 carriers: https://doi.org/10.1200/jco.2012.47.8313
- NICE NG101: early and locally advanced breast cancer (receptor testing 1.3, genetic testing 1.3.6, triple-negative section 1.8): https://www.nice.org.uk/guidance/ng101/chapter/Recommendations
- NICE CG164: familial breast cancer (referral, genetic testing, surveillance, risk-reducing surgery, chemoprevention): https://www.nice.org.uk/guidance/cg164/chapter/Recommendations
- NICE TA886: olaparib for adjuvant treatment of BRCA mutation-positive HER2-negative high-risk early breast cancer (May 2023): https://www.nice.org.uk/guidance/ta886

## Connected records

- cancers: [Basal-like 1 triple-negative breast cancer (BL1)](https://onco.cc/cancers/tnbc-basal-like-1/), [Carcinoma with medullary pattern (medullary breast cancer)](https://onco.cc/cancers/medullary-pattern-breast-carcinoma/), [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [Metastatic triple-negative breast cancer](https://onco.cc/cancers/tnbc-metastatic/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/), [Platinum agents](https://onco.cc/technologies/platinum/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [PARP](https://onco.cc/targets/parp/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Olaparib](https://onco.cc/drugs/olaparib/), [Talazoparib](https://onco.cc/drugs/talazoparib/)
- pathways: [DNA damage response & homologous recombination](https://onco.cc/pathways/ddr/)
- terms: [Basal-like breast cancer](https://onco.cc/terms/basal-like/), [Chemoprevention (tamoxifen, anastrozole, raloxifene) and ER-negative breast cancer](https://onco.cc/terms/chemoprevention-and-er-negative-breast-cancer/), [Founder mutation (BRCA1 185delAG and 5382insC, BRCA2 6174delT)](https://onco.cc/terms/founder-mutation/), [Germline BRCA testing criteria for triple-negative breast cancer (UK)](https://onco.cc/terms/germline-brca-testing-criteria-tnbc/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Homologous recombination deficiency (HRD) in breast cancer](https://onco.cc/terms/hrd-in-breast-cancer/), [Interval breast cancer (a cancer found between screening rounds)](https://onco.cc/terms/interval-breast-cancer/), [Invasive disease-free survival (iDFS)](https://onco.cc/terms/idfs/), [Mastectomy](https://onco.cc/terms/mastectomy/), [Risk-reducing surgery for BRCA carriers (bilateral and contralateral mastectomy, salpingo-oophorectomy)](https://onco.cc/terms/risk-reducing-surgery-brca-carriers/)
- trials: [EMBRACA](https://onco.cc/trials/embraca/), [OlympiA](https://onco.cc/trials/olympia/), [OlympiAD](https://onco.cc/trials/olympiad/)

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JSON: https://onco.cc/api/v1/entities/brca-associated-tnbc.json