BRCA1 and BRCA2 hereditary breast and ovarian cancer

At a glance

• BRCA1 (17q21) and BRCA2 (13q13) are tumour suppressor genes needed for homologous recombination repair of double-strand DNA breaks. Inheritance is autosomal dominant, and cancer follows loss of the second allele in a cell (the two-hit model).
• About 1 in 400 people carry a pathogenic variant; about 1 in 40 with Ashkenazi Jewish ancestry.
• Carriers have lifetime breast cancer risk around 70% and ovarian cancer risk of 44% (BRCA1) or 17% (BRCA2).
• Risk-reducing salpingo-oophorectomy (RRSO) saves lives. Ovarian screening doesn't.
• Testing now changes treatment for people with cancer (PARP inhibitors, surgery) as well as prevention for relatives.

Breast cancer biology and treatment are in Breast cancer; BRCA in pancreatic cancer is in Pancreatic cancer.

Cancer risks

Lifetime risk to age 80 (eviQ, from the Kuchenbaecker prospective cohort):

Cancer	BRCA1	BRCA2	General population
Female breast	72%	69%	11%
Ovarian, tubal, peritoneal	44%	17%	0.8%
Male breast	0.4%	3.8%	0.1%
Prostate	Possible small increase	27%, often aggressive	18%
Pancreatic	2 to 3%	3 to 4%	1 to 1.4%

• Ovarian cancer in BRCA carriers is high-grade serous, much of it starting in the fallopian tube fimbria (serous tubal intraepithelial carcinoma, STIC). Risk rises from the late 30s in BRCA1 and the late 40s in BRCA2.
• BRCA1 breast cancers are usually triple-negative and high grade. BRCA2 cancers are more often hormone receptor positive.
• Contralateral breast cancer risk after a first cancer is about 40% at 20 years for BRCA1 and 26% for BRCA2.
• Melanoma risk is not raised enough to change care (eviQ removed it in 2012).

Who to refer and test

Testing is usually done through a familial cancer centre. Oncologists and surgeons now also order "mainstream" testing in people with cancer, with genetic counselling after the result.

Test a person with cancer (Medicare funds testing in affected people who meet criteria) such as:

• High-grade non-mucinous epithelial ovarian, tubal or peritoneal cancer at any age
• Triple-negative breast cancer under 60
• Breast cancer under 40, bilateral breast cancer, or male breast cancer
• Breast cancer with Ashkenazi ancestry
• Metastatic prostate cancer or pancreatic cancer (germline testing for all with pancreatic adenocarcinoma)
• A 10% or higher predicted chance of a pathogenic variant on a validated tool (Manchester score, CanRisk/BOADICEA)

Test unaffected relatives when a pathogenic variant is known in the family (cascade testing, Medicare funded for biological relatives). First-degree relatives have a 50% chance of carrying it. When no living affected relative can be tested, an unaffected person can sometimes be tested directly through a familial cancer centre.

Interpreting results

Result	Meaning
Pathogenic or likely pathogenic	Manage as a carrier; offer cascade testing
Variant of uncertain significance	Not actionable. Manage on family history, and don't use it for predictive testing of relatives
No variant found, family variant known	True negative: population risk for that gene
No variant found, no family variant known	Uninformative: the family may carry a variant the test missed, or in another gene. Manage on family history

• Panel tests also find PALB2 (high risk), CHEK2 and ATM (moderate risk), and the ovarian genes RAD51C, RAD51D and BRIP1.
• Biallelic BRCA2 causes Fanconi anaemia (FANCD1); two carriers can have an affected child.

Pitfall: a negative test in an unaffected woman only reassures if the family's variant has already been found. Otherwise test an affected relative first.

Risk management in women

Ovaries and tubes

• RRSO at 35 to 40 for BRCA1 and 40 to 45 for BRCA2, after childbearing. It cuts ovarian cancer risk by about 80 to 95% and lowers all-cause mortality.
• Pathology uses the SEE-FIM protocol to look for occult cancer and STIC. A small primary peritoneal cancer risk remains.
• After RRSO without a breast cancer history, menopausal hormone therapy until the average age of natural menopause (about 51) treats symptoms and protects bone and heart, without cancelling the breast benefit.
• No ovarian screening: CA125 and transvaginal ultrasound do not reduce mortality, and eviQ advises against offering them.
• Salpingectomy with delayed oophorectomy is being studied in trials but is not standard.
• The combined pill lowers ovarian cancer risk, but eviQ doesn't recommend it for prevention because RRSO is far more effective.
• Routine hysterectomy isn't recommended.

Breasts

Age	eviQ surveillance
Start at 25 to 30, to 39	Annual MRI (start age individualised with CanRisk or iPrevent; no mammogram before 40)
40 to 60	Annual MRI plus mammogram
Over 60	Annual mammogram; consider CEM, or add MRI or ultrasound if breasts are dense
Pregnant or breastfeeding	Ultrasound and clinical examination

• Bilateral risk-reducing mastectomy cuts breast cancer risk by 90% or more. Timing is individual.
• Chemoprevention: tamoxifen before menopause; tamoxifen, raloxifene or an aromatase inhibitor after menopause, for women not planning surgery within 3 years. Evidence in BRCA1 carriers is weakest because their cancers are mostly receptor negative.
• If MRI isn't possible, eviQ offers contrast-enhanced mammography (CEM) or ultrasound instead.
• Medicare funds breast MRI for high-risk women under 50.

Pancreas

• Surveillance (endoscopic ultrasound or MRI from 50) only for carriers with an affected first- or second-degree relative, ideally in a trial such as the Australian APRISE study.

Risk management in men

• BRCA2: annual PSA from 40, with or without DRE. Consider the same for BRCA1.
• Chest awareness. Annual mammography from 50 may be considered in BRCA2 carriers (or 10 years before the youngest male breast cancer in the family).
• Men pass the variant to half their children, including daughters. Fathers are often forgotten in pedigree assessment.

Treatment implications in people with cancer

• PARP inhibitors (olaparib, niraparib, talazoparib) exploit synthetic lethality. PBS listings, each with criteria, cover olaparib or niraparib for maintenance in BRCA-mutated ovarian cancer, olaparib or niraparib for first-line maintenance of advanced ovarian cancer with genomic instability (HRD-positive) but no BRCA variant, and olaparib for high-risk early breast cancer and metastatic prostate cancer. Check the current PBS Schedule for each restriction, as these change.
  • OlympiA: a year of adjuvant olaparib in high-risk HER2-negative early breast cancer with a germline BRCA variant improved invasive disease-free and overall survival.
  • SOLO-1: olaparib maintenance after first-line platinum in advanced BRCA-mutated ovarian cancer gave a large, durable progression-free survival gain.
  • POLO: olaparib maintenance in germline BRCA metastatic pancreatic cancer (progression-free survival only).
• BRCA-mutated cancers respond well to platinum chemotherapy.
• A carrier with a new breast cancer may choose bilateral mastectomy over breast conservation because of contralateral and ipsilateral risk. Radiotherapy is not contraindicated (unlike TP53).

Ethical and practical issues

• Predictive testing of children for BRCA is deferred until adulthood, because no intervention starts before 25.
• Reproductive options: preimplantation genetic testing with IVF, or prenatal diagnosis.
• Life insurance: the Treasury Laws Amendment (Genetic Testing Protections in Life Insurance and Other Measures) Act 2026 stops life insurers asking for or using genetic test results (the person's or a relative's, or whether a test was done) to refuse or limit cover. It applies to underwriting decisions from 8 October 2026 (6 months after Royal Assent on 8 April 2026) and replaces the industry moratorium. ASIC enforces it and complaints go to AFCA. Insurers can still use family history, symptoms and diagnosed disease, so a carrier who has had cancer is assessed on that. Health insurance is community rated and unaffected.
• Telling relatives is the patient's job, with letters from the family cancer centre. The Privacy Act allows disclosure to relatives without consent only in narrow circumstances to prevent serious threat, following NHMRC guidelines.

Pitfalls

• Ovarian screening offered instead of RRSO.
• Testing an unaffected relative first when an affected relative is alive. A negative result is then uninformative.
• Acting on a variant of uncertain significance with surgery or cascade testing.
• Ignoring the paternal line. Half of carriers inherited the variant from their father.
• Forgetting men: BRCA2 raises the risk of aggressive prostate cancer and male breast cancer.
• Testing children for an adult-onset condition.