BRCA Mutation (BRCA1 and BRCA2)

How BRCA genes work

Everyone has two copies of BRCA1 and BRCA2. Their proteins help repair broken DNA strands. A harmful variant in one copy is inherited. If the second copy in a cell is later damaged, that cell loses its repair ability and can become cancerous. This is why carriers have higher risk, but not certainty, of cancer.

Cancer risks

Estimated lifetime risks, which vary by study and family history:

BRCA1-related breast cancers are often "triple negative" and appear at younger ages. BRCA2 is more strongly linked to male breast, prostate and pancreatic cancer. Melanoma risk may also be modestly raised with BRCA2.

Who should consider testing

Genetic testing is recommended for people with:

• a personal history of breast cancer diagnosed at 50 or younger, triple-negative breast cancer, bilateral breast cancer, or male breast cancer
• a personal history of ovarian cancer, pancreatic cancer or metastatic prostate cancer
• a close relative with a known BRCA mutation
• a strong family history of these cancers, especially on the same side of the family
• Ashkenazi Jewish ancestry with a relevant personal or family history

Many people are now tested with multi-gene panels that also check genes such as PALB2, CHEK2, ATM and the Lynch syndrome genes.

What the test results mean

• Positive (pathogenic variant): you carry a harmful mutation and have increased risk. Relatives can then be tested for the same variant.
• Negative, with a known family mutation: you did not inherit it; your risk is close to average.
• Negative, without a known family mutation: reassuring but does not rule out other hereditary causes.
• Variant of uncertain significance (VUS): a gene change whose effect is unknown. Most are later reclassified as harmless. Decisions are based on family history, not the VUS.

Genetic counseling before and after testing helps you understand results and their implications for family members. In the US, the Genetic Information Nondiscrimination Act (GINA) prevents health insurers and most employers from using genetic results against you, though it does not cover life, disability or long-term care insurance.

Managing risk if you carry a BRCA mutation

Screening

For women, guidelines typically recommend:

• breast awareness from age 18
• clinical breast exams every 6 to 12 months from age 25
• annual breast MRI from age 25 and annual mammography added from age 30

There is no reliable screening test for ovarian cancer, which is why preventive surgery is advised.

For men: breast self-exams and clinical exams from age 35, and prostate cancer screening from age 40 (especially BRCA2). Pancreatic cancer screening may be offered to carriers with a family history of pancreatic cancer.

Risk-reducing surgery

• Risk-reducing salpingo-oophorectomy (removal of ovaries and fallopian tubes) reduces ovarian cancer risk by about 80 to 90%. It is usually recommended between ages 35 and 40 for BRCA1 carriers, and 40 to 45 for BRCA2, once childbearing is complete. It causes early menopause, so hormone therapy is often considered for those without breast cancer.
• Risk-reducing mastectomy reduces breast cancer risk by about 90% or more. Breast reconstruction is an option.

Medicines

• Tamoxifen or aromatase inhibitors may reduce breast cancer risk in some carriers.
• Birth control pills reduce ovarian cancer risk, though their effect on breast cancer risk in carriers is debated.

Treatment if cancer develops

BRCA status guides treatment. PARP inhibitors (olaparib, niraparib, rucaparib, talazoparib) are particularly effective in BRCA-related breast, ovarian, prostate and pancreatic cancers. Platinum chemotherapy also works well.

Family implications

First-degree relatives (parents, siblings, children) each have a 50% chance of carrying the same mutation. Testing children is usually deferred until adulthood, since results do not change care in childhood. Families can also consider reproductive options such as preimplantation genetic testing.

Frequently asked questions

What is the difference between BRCA1 and BRCA2?

Both raise breast and ovarian cancer risk. BRCA1 carries a higher risk of ovarian cancer and earlier, often triple-negative breast cancer. BRCA2 is more strongly linked to male breast cancer, prostate cancer and pancreatic cancer.

Does a BRCA mutation mean I will get cancer?

No. It raises your risk substantially, but many carriers never develop cancer. Screening, preventive medicines and risk-reducing surgery can greatly lower risk or allow cancers to be found early.

Can men have a BRCA mutation?

Yes. Men inherit and pass on BRCA mutations as often as women. Male carriers have higher risks of breast, prostate and pancreatic cancer, and their children each have a 50% chance of inheriting the mutation.

Should I get a BRCA test?

Consider testing if you have a personal or family history of early breast cancer, ovarian, pancreatic or metastatic prostate cancer, male breast cancer, a relative with a known mutation, or Ashkenazi Jewish ancestry with relevant family history. Start with genetic counseling.