Clinical reference

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BRCA1

Established

BRCA1 germline mutations confer major hereditary breast/ovarian cancer risk and determine PARP inhibitor treatment eligibility.

Also known as BRCA1 breast cancer gene 1
In plain language

BRCA1 is a gene that normally helps repair DNA damage. When it's mutated, both breast and ovarian cancer risk rise substantially, and tumors become vulnerable to specific targeted drugs that further block DNA repair. Testing recommendations have expanded significantly, now including many patients who wouldn't have met older family-history-based testing criteria.

Biomarker & context

BRCA1 is a tumor suppressor gene central to homologous recombination DNA repair; germline pathogenic variants substantially increase lifetime risk of breast and ovarian cancer and are one of the most clinically actionable hereditary cancer genes in current practice.

What it indicates

BRCA1 pathogenic variants confer markedly elevated lifetime breast and ovarian cancer risk and determine eligibility for PARP inhibitor therapy (olaparib, talazoparib, and others), which exploits the DNA-repair deficiency these mutations create in tumor cells (a mechanism called synthetic lethality).

Diagnosis & clinical testing

Detected via germline genetic testing (blood or saliva sample) for hereditary risk assessment, or somatic tumor testing to determine PARP inhibitor eligibility even without a germline mutation; testing criteria have broadened considerably, with guidelines now recommending BRCA testing for essentially all metastatic castration-resistant prostate cancer patients regardless of family history, since nearly half of BRCA-related prostate cancer cases lack typical family history criteria.

Guiding treatment

The ASCO-endorsed OlympiA trial results support one year of adjuvant olaparib for early-stage, high-risk, HER2-negative breast cancer with a germline BRCA1/2 mutation, with 2024 updated follow-up data showing a 28% mortality risk reduction; BRCA1-positive breast cancers are also more likely to be triple-negative, influencing initial treatment selection even before genetic results return.

Clinical significance

Testing criteria have broadened well beyond family history alone, especially in metastatic prostate cancer.

References
  1. NCI. BRCA Gene Changes: Cancer Risk and Genetic Testing Fact Sheet.
  2. European Journal of Cancer. Clinical practice guidelines for BRCA1 and BRCA2 genetic testing.
  3. ASCO. New ASCO Guideline Recommends Adjuvant Olaparib for Patients with Hereditary Breast Cancer.