What Does a BRCA Tumor Mutation Mean?

This page is for people whose tumor test report shows a BRCA1 or BRCA2 change. It explains what the result means, how it can affect treatment, and what it may mean for your family.

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 sort them into groups. Ask your care team how your lab classifies it:

• Pathogenic or likely pathogenic (harmful or likely harmful) changes are the ones that matter.
• A variant of uncertain significance is a finding nobody can yet act on.
• 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.

NCI says drugs that damage DNA, such as cisplatin, can work well against tumors with a BRCA change. The FDA has approved four PARP inhibitors (pills) for BRCA-linked cancers: olaparib, rucaparib, niraparib and talazoparib. These are results across groups of people, not a promise about one tumor.

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 tumor, 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 tumor-only finding, or a variant of uncertain significance, tells your relatives nothing, and the figures below do not apply to them. With that established, people who inherit a harmful BRCA1 or BRCA2 change face real added risk:

• Breast cancer (women): lifetime risk above 60%, compared with about 13% for women overall.
• Ovarian cancer: about 39% to 58% for BRCA1 carriers and 13% to 29% for BRCA2 carriers, compared with about 1.1% for women overall.
• Pancreatic cancer: BRCA2 changes raise the risk to roughly 5% to 10%.
• Prostate cancer: BRCA2 changes raise the risk in men 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.

• Has inherited (germline) testing been arranged, to find out if my change was inherited?
• Does a PARP inhibitor or platinum chemotherapy fit my specific cancer type?
• What does my BRCA result mean for my family, and is genetic counseling available to them?
• Was it BRCA1 or BRCA2? The two carry somewhat different risks.

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