Conditions · Metabolism (biochemistry)
Hereditary breast and ovarian cancer syndrome (BRCA1/BRCA2) !
Inherited BRCA1 or BRCA2 variants that sharply raise the risk of breast and ovarian cancer, and also of prostate and pancreatic cancer.
Updated 2026-11-01
Structures involved
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In biochemistry
In the clinical exam
Why it happens
- Genomic instability: mismatch repair, BRCA and xeroderma pigmentosum
- Hereditary cancer syndromes: the table to know
- Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis
- Molecular pathology: PCR, FISH, sequencing and liquid biopsy
What it is
An autosomal dominant cancer predisposition caused by germline variants in BRCA1 or BRCA2, genes of double-strand break repair by homologous recombination.
Who gets it
BRCA variants explain a small but important share of breast cancer (about 5–10% of cases have a hereditary cause) and a larger share of high-grade serous ovarian cancer. They are more common in some founder populations (such as Ashkenazi Jewish). Founder BRCA1 and BRCA2 variants have been described in Colombia in regional studies; no population prevalence is established.
Causes
- Inherited pathogenic variant in BRCA1 (chromosome 17) or BRCA2 (chromosome 13)
- Loss of the second copy in the tissue (two hits)
- Other homologous recombination genes with lower risk: PALB2, RAD51C, RAD51D, ATM, CHEK2
Risk factors
- Relatives with breast cancer before 50, bilateral or in men
- Ovarian cancer in the family
- Ancestry with founder variants
- Triple-negative breast cancer at a young age
Pathophysiology
BRCA1 helps detect and resect double-strand breaks and BRCA2 loads the RAD51 recombinase onto single-stranded DNA. Without them, the cell cannot use the sister chromatid as a template and repairs by error-prone routes (NHEJ, microhomology-mediated joining). Deletions and rearrangements build up (chromosomal instability), which favours cancer in hormone-sensitive tissues. The same defect makes them sensitive to platinum and PARP inhibitors (synthetic lethality).
Classification
- BRCA1: more triple-negative breast cancer and ovarian cancer
- BRCA2: more hormone receptor-positive breast cancer, male breast, prostate and pancreatic cancer
- Two altered BRCA2 copies: Fanconi anaemia (group D1)
Symptoms and signs
- No symptoms until a cancer appears
- Breast lump, nipple retraction or bloody discharge
- Abdominal bloating, early satiety or persistent pelvic pain (ovary)
Diagnosis
- Clinical
- Suspected from personal and family history criteria; testing is offered to all patients with epithelial ovarian cancer and many with young-onset or triple-negative breast cancer.
- Tests
- Hereditary cancer gene panel by sequencing (BRCA1, BRCA2, PALB2 and others) with large-deletion analysis; CA-125 in ovarian cancer follow-up.
- Imaging
- Breast MRI and mammography for surveillance; transvaginal ultrasound when pelvic symptoms are evaluated.
Treatment
- Follow-up
- Intensive breast surveillance: yearly MRI from a young age and mammography later, by age and gene.
- Surgical
- Risk-reducing bilateral mastectomy (optional, shared decision).
- Surgical
- Risk-reducing bilateral salpingo-oophorectomy once childbearing is complete, because ovarian cancer screening is not effective.
- Medical
- PARP inhibitors and platinum chemotherapy in BRCA-deficient tumours.
- Follow-up
- Genetic counselling and cascade testing of relatives, men included.
Complications
- Breast cancer (often early and bilateral)
- Ovarian, fallopian tube and peritoneal cancer
- Aggressive prostate cancer (BRCA2)
- Pancreatic cancer and melanoma (BRCA2)
Prognosis
Surveillance and risk-reducing surgery greatly lower mortality. Salpingo-oophorectomy cuts ovarian cancer risk by more than 80%.
Prevention
- Genetic counselling before and after testing
- Risk-reducing surgery in carriers
- Surveillance by gene and age
Test yourself
Think of the answer, then tap the question to see it.
Which DNA repair pathway depends on BRCA1 and BRCA2?
Homologous recombination, which repairs double-strand breaks using the sister chromatid.
Why do BRCA-deficient tumours respond to PARP inhibitors?
Without homologous recombination they rely on PARP for repair; blocking both routes kills the tumour cell (synthetic lethality).
Which cancers are more typical in men with BRCA2 variants?
Male breast cancer, aggressive prostate cancer and pancreatic cancer.
Why is risk-reducing salpingo-oophorectomy advised instead of ovarian screening?
Because there is no effective screening for ovarian cancer, which is usually found late.
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Breast cancer: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Ovarian cancer: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); BRCA1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); BRCA2 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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