BRCA1 and BRCA2 testing

What it is

BRCA1 and BRCA2 testing is a blood or saliva genetic test that looks for inherited harmful variants linked to higher cancer risk. BRCA1 and BRCA2 are tumour-suppressor genes involved in DNA repair, and harmful inherited variants in either gene can substantially raise lifetime risk of breast and ovarian cancer, with BRCA1 generally carrying a higher ovarian cancer risk than BRCA2. The test does not diagnose cancer by itself. Instead, it helps estimate inherited cancer susceptibility and can guide screening, risk-reducing surgery, family testing, and in some people with cancer, treatment decisions.

BRCA testing is usually considered when a person or family has features suggesting hereditary breast and ovarian cancer syndrome rather than average population risk. Men and women can both carry and pass on BRCA1 or BRCA2 variants. In India, the same principles apply: testing is most useful when guided by personal cancer history, family history, age at diagnosis, and access to genetic counselling.

A BRCA test may be ordered as a focused BRCA1/2 test or as part of a multigene hereditary cancer panel.

Test type	What it looks for	Common use
BRCA1/2-only test	Harmful variants in BRCA1 and BRCA2	When the question is specifically about BRCA-associated risk
Multigene panel	BRCA1/2 plus other cancer-risk genes	When family history suggests inherited cancer but not only BRCA
Single-site family variant test	One known familial variant	Testing relatives after a pathogenic family variant is found

How it works

BRCA1 and BRCA2 help repair damaged DNA, especially double-strand breaks through homologous recombination repair. When a person inherits a harmful variant in one copy of BRCA1 or BRCA2, cells have less ability to repair DNA accurately. Over time, additional genetic damage can accumulate, increasing the chance that certain cancers develop.

The laboratory analyzes DNA from blood or saliva to look for pathogenic or likely pathogenic variants. Results are usually reported in one of several categories:

1. Positive for a pathogenic or likely pathogenic variant: an inherited change known, or very likely, to increase cancer risk.
2. Negative: no harmful BRCA1/2 variant was found, though this does not remove all cancer risk.
3. Variant of uncertain significance, or VUS: a DNA change was found, but current evidence cannot say whether it is harmful.

A VUS should generally not be used on its own to make major preventive decisions. Over time, some VUS results are reclassified as more evidence becomes available.

Evidence and uses

BRCA1/2 testing has been used clinically for more than 25 years and is well established in hereditary cancer care. It is most often used in these situations:

• A strong personal or family history of breast, ovarian, pancreatic, or prostate cancer
• Breast cancer at a young age
• Triple-negative breast cancer in some patients
• Male breast cancer
• More than one BRCA-associated cancer in the same person or family
• A known pathogenic BRCA variant in a relative

For people without cancer, a positive result can support earlier or more intensive screening and discussion of risk-reducing options. For people who already have cancer, BRCA status may affect treatment planning. In breast, ovarian, pancreatic, and prostate cancers, BRCA-related homologous recombination deficiency can make some tumours more likely to respond to platinum chemotherapy or PARP inhibitors, depending on the cancer type and clinical setting.

The test is informative, but it has limits. A negative result can mean different things. If a known family variant is absent, that is often reassuring. But if no affected relative has been tested first, a negative result may be less informative because the family risk could be due to another gene not included in the test, or to a variant not yet understood.

Current evidence also shows that BRCA1 and BRCA2 do not confer identical risks. Both increase breast and ovarian cancer risk, but BRCA1 is generally associated with a higher ovarian cancer risk, while BRCA2 is also strongly linked with male breast cancer, pancreatic cancer, and prostate cancer. Exact risk estimates vary by study, ancestry, family history, and the specific variant.

Diagnosis / how it's measured

BRCA testing is done on a blood sample or saliva sample. The laboratory uses DNA sequencing, and often methods that also detect larger deletions or duplications, to identify inherited variants. The result is interpreted together with personal and family history.

Pre-test genetic counselling is important because the result can affect not only the person tested but also blood relatives. Counselling usually covers:

• What the test can and cannot tell you
• Possible results and what each means
• The chance of uncertain findings
• Implications for relatives, including children, siblings, and parents
• Privacy, emotional impact, and follow-up planning

Post-test counselling is equally important. A positive result may lead to referral for high-risk screening or surgical consultation. A negative or uncertain result may still need specialist interpretation, especially if the family history remains strongly suggestive of inherited cancer.

In practice, clinicians often prefer to test an affected family member first, if possible, because that gives the best chance of identifying a familial pathogenic variant. Testing an unaffected person first can still be useful, but interpretation may be less clear.

When to see a clinician

Consider speaking with an oncologist, breast specialist, gynecologic oncologist, or genetic counsellor if you have breast cancer at a young age, ovarian cancer at any age, triple-negative breast cancer, male breast cancer, pancreatic cancer, metastatic or high-risk prostate cancer, or a close relative with one of these cancers. You should also ask about testing if multiple relatives on the same side of the family had related cancers, especially at younger ages.

If you already have a BRCA test result, see a clinician if the report mentions a pathogenic variant, likely pathogenic variant, or VUS and you have not had formal counselling. Family members may also need cascade testing when a pathogenic familial variant is found.

In India, testing quality and interpretation can vary by laboratory, so it is reasonable to ask whether the lab is experienced in hereditary cancer testing and whether genetic counselling is available before and after the test.

Limitations and open questions

BRCA1/2 testing is powerful, but it does not predict with certainty who will or will not get cancer. A positive result means increased risk, not a diagnosis. A negative result does not rule out hereditary cancer from other genes or unknown variants. A VUS can be stressful because it often does not change management until more evidence emerges.

Another limitation is that risk estimates are not identical across all populations. Much of the published data comes from European-ancestry cohorts, although evidence from more diverse populations is growing. This matters in countries such as India, where founder variants may differ by region or community and where access to counselling and preventive care is uneven.

Evidence continues to evolve on the best use of multigene panels, how to interpret moderate-risk genes alongside BRCA1/2, and how often uncertain variants should be re-reviewed. The most useful BRCA testing is not just the lab result itself, but the combination of a high-quality test, careful counselling, and a management plan tailored to the person's history and goals.