Breast cancer genetic testing: which genes, who should test, and the limits

It is a test of the DNA you were born with for variants that raise the chance of breast cancer, and usually of ovarian cancer too, since many of the same genes are behind both.^[3] It looks for inherited risk, not for cancer.

Most breast cancer isn’t inherited. In most cases the gene changes behind it build up during a person’s life, only in the breast cells, and age, hormones and family history all shape risk as well.^[1] Testing speaks to the smaller share that runs in families.

BRCA1 and BRCA2 are the best known. Harmful variants in either raise the risk of breast and ovarian cancer a great deal, and of prostate and pancreatic cancer too;^[2] BRCA1 and BRCA2 testing, explained covers them on their own. NCI’s summary for health professionals groups the other genes by how much a harmful variant raises risk: high penetrance means a large rise, moderate penetrance a smaller one.^[3]

Two more moderate-penetrance genes linked with breast and ovarian cancer, RAD51C and RAD51D,^[3] are not checked by GeneCancer, our at-home test of selected variants by genotyping. Where ovarian cancer runs in a family, that is one more reason to start with a clinician-ordered test.

• If you have been diagnosed. NCI notes that clinical practice guidelines recommend genetic testing for anyone diagnosed with triple-negative breast cancer, ovarian cancer or breast cancer in a man, among other cancers, partly because the result can help choose treatment.^[4] Ask your cancer care team.
• If breast or ovarian cancer runs in your family. The USPSTF’s 2019 advice asks clinicians to assess women whose own or family history includes breast, ovarian, fallopian tube or peritoneal cancer, or whose ancestry is linked with BRCA1 or BRCA2 variants, and to send those at raised risk to genetic counseling.^[5]
• If a relative carries a known variant, in BRCA1, BRCA2 or any of the genes above. Testing can then look for that same change, or read the whole gene.^[4]
• Men too. Men inherit and pass on these variants, and breast cancer in a man is one of the diagnoses guidelines single out.^[4]

The same USPSTF advice recommends against routine BRCA testing for women with none of that history.^[5] Who should consider genetic testing for cancer sets out the family patterns for every inherited cancer.

Most people are tested through a clinician or a genetic counselor, who orders a multigene panel: one test that reads BRCA1, BRCA2 and a chosen set of the other genes in full, picked to fit the family’s history. NCI’s summary notes the catch: a panel can report genes whose effect on risk is small or unclear, and variants of uncertain significance.^[3]

A test you order yourself usually checks selected variants, known positions picked in advance, instead of reading genes. At-home or clinical testing? compares the two routes.

Checks selected variants across 108 genes, including BRCA1 and BRCA2, by genotyping. Which genes are linked with breast and ovarian cancer is the general science in the table above; which variants GeneCancer checks in each of its genes isn’t published yet. It doesn’t read whole genes, so it can miss a harmful variant even in a gene it looks at, and a result with none found can’t rule out inherited risk.

Selected variants only, by genotyping. Not a full-gene test.

It doesn’t check RAD51C or RAD51D.

If you or a close relative has had cancer, ask your doctor about full-gene clinical testing.

• A harmful variant found. How much it matters depends on the gene: a variant in a high-penetrance gene such as BRCA1, BRCA2 or PALB2 raises risk more than one in a moderate-penetrance gene such as CHEK2 or ATM.^[3] A finding from a test of selected variants needs a clinical test to confirm it before any decision.^[6] After a positive BRCA result walks through what comes next for BRCA.
• Nothing found. It speaks only for what the test read. After a test of selected variants, harmful variants elsewhere in the same genes weren’t looked at.
• A variant of uncertain significance. A change whose effect nobody knows yet. Your clinician reads it alongside your family history, and it isn’t a reason to act on its own.^[3]

• Whether you have breast cancer. It reads inherited risk. A lump or any other change needs your doctor, whatever a gene result says.
• Your whole risk. Age, hormones, earlier breast changes and family history all count, whatever the genes show.^[1]
• Whether you will get cancer. A harmful variant raises the chance; it doesn’t decide it. Not everyone who inherits one in BRCA1 or BRCA2 develops cancer.^[2]
• Which choices to make. Extra checks, medicines or surgery are decisions for you and your clinician, once a finding is confirmed.

If you have had breast or ovarian cancer, or either runs in your family, start with a clinician-ordered test that reads the genes in full.

With no such history, USPSTF advises against routine testing.^[5] If you choose to test anyway, GeneCancer can tell you whether you carry any of its selected variants, checked by genotyping. It looks at chosen positions rather than whole genes, so a result with none found doesn’t rule out inherited risk, and any variant it finds goes to your clinician for a clinical test.

Selected variants only, by genotyping. Not a full-gene test.