What Does a BRCA Tumor Mutation Mean?

A BRCA tumor mutation means testing of the cancer found a change in the BRCA1 or BRCA2 gene. These genes normally help repair broken DNA. When they do not work right, DNA damage builds up more easily. Tumor testing alone usually cannot say whether the change was inherited. It also cannot say whether the change only arose in the cancer cells. A separate blood or saliva test, called germline testing, is often needed to sort that out.

There is a second thing the word "change" hides. Not every BRCA change is harmful. Reports classify them: pathogenic or likely pathogenic changes are the ones that matter, while a variant of uncertain significance is a finding nobody can yet act on, and some changes are simply harmless. Ask which classification your report gives, which gene it is in, and whether one copy or both are affected. Everything below depends on that answer.

This result can show up in breast, ovarian, prostate, pancreatic, and other cancers. Not everyone with these cancers needs, or benefits from, the same testing or treatment.

Cancers driven by a harmful BRCA change tend, as a group, to be more sensitive to platinum chemotherapy and to a class of pills called PARP inhibitors: olaparib, rucaparib, niraparib and talazoparib. Tend as a group is the important part. It is a shift in the odds across many people, not a promise about one tumour.

Whether any of it applies to you is narrower still. It depends on which gene, how the variant was classified, the cancer type, whether the change is inherited or confined to the tumour, where you are in the course of treatment, and what each drug's current approval actually covers. Those approvals differ between cancers and they change. Ask your oncologist to walk through the exact wording of the approval for the drug being proposed, rather than working from a general rule.

This part only comes into play once germline testing has confirmed an inherited change and that change has been classified as pathogenic or likely pathogenic. A tumour-only finding, or a variant of uncertain significance, tells your relatives nothing, and the figures below do not apply to them. With that established: women who inherit a harmful BRCA1 or BRCA2 change face real added risk. Their lifetime breast cancer risk runs above 60%. For comparison, women overall face about a 13% lifetime risk. Ovarian cancer risk runs about 39% to 58% for BRCA1 carriers. It runs 13% to 29% for BRCA2 carriers. Women overall face about a 1% risk. BRCA2 changes also raise pancreatic cancer risk, to roughly 5% to 10%. They raise prostate cancer risk in men too, as high as 61% by age 80. Genetic counseling can help relatives understand their own risk. It can help them decide whether to get tested themselves.

Finding a BRCA change in your tumor does not by itself mean you inherited it. It does not by itself mean your relatives are at risk. That distinction only comes from germline testing. A BRCA change also does not guarantee a PARP inhibitor or platinum chemotherapy will work. It raises the odds of benefit. It does not decide any one person's outcome.

The result itself is not an emergency. But if germline testing has not been arranged, it is worth raising promptly. It affects both your own treatment options and whether your family should consider testing.

Ask whether inherited (germline) testing has been arranged, to find out if your change was inherited. Ask whether a PARP inhibitor or platinum chemotherapy fits your specific cancer type. Ask what your BRCA result means for your family, and whether genetic counseling is available to them. Ask whether it was BRCA1 or BRCA2, since the two carry somewhat different risks.

• NCI — BRCA Gene Changes: Cancer Risk and Genetic Testing