What are the implications of having a BRCA1 or BRCA2 mutation for breast and ovarian cancer prognosis and treatment?

A number of studies have investigated possible differences between breast and ovarian cancers that are associated with harmful BRCA1 or BRCA2 mutations and cancers that are not associated with these mutations. There is some evidence that, over the long term, women who carry these mutations are more likely to develop a second cancer in both the same (ipsilateral) breast and the opposite (contralateral) breast than women who do not carry these mutations.

Thus, some women with a harmful BRCA1 or BRCA2 mutation who develop breast cancer in one breast opt for a bilateral mastectomy, even if they would otherwise be candidates for breast-conserving surgery. In fact, because of the increased risk of a second breast cancer among BRCA1 and BRCA2 mutation carriers, some doctors recommend that women with early-onset breast cancer and those whose family history is consistent with a mutation in one of these genes have genetic testing at diagnosis.

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Breast cancers in women with a harmful BRCA1 mutation are also more likely to be triple-negative cancers, and these cancers generally have poorer prognosis than other breast cancers. However, one study found that, among women with ovarian cancer, those with a harmful BRCA1 or BRCA2 mutation were more likely to survive for 5 years than those without such a mutation. The outcomes were best among women with a BRCA2 mutation.28

Because the products of the BRCA1 and BRCA2 genes are involved in DNA repair, some investigators have suggested that cancer cells with a harmful mutation in either of these genes may be more sensitive to anticancer agents that act by damaging DNA, such as cisplatin.

In preclinical studies, drugs called PARP inhibitors, which block the repair of DNA damage, have been found to arrest the growth of cancer cells that have BRCA1 or BRCA2 mutations. These drugs have also shown some activity in cancer patients who carry BRCA1 or BRCA2 mutations, and researchers are continuing to develop and test these drugs.

What research is currently being done to help individuals with harmful BRCA1 or BRCA2 mutations?

Research studies are being conducted to find new and better ways of detecting, treating, and preventing cancer in people who carry mutations in BRCA1 and BRCA2. Additional studies are focused on improving genetic counseling methods and outcomes. Our knowledge in these areas is evolving rapidly. Information about active clinical trials (research studies with people) for individuals with BRCA1 or BRCA2 mutations is available on NCI’s website. The following links will retrieve lists of clinical trials open to individuals with BRCA1 or BRCA2 mutations.

  • BRCA1 mutation carriers
  • BRCA2 mutation carriers

NCI’s Cancer Information Service (CIS) can also provide information about clinical trials and help with clinical trial searches.

Selected References

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  15. U.S. Preventive Services Task Force. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: Recommendation Statement. Retrieved August 8, 2009, from: http://www.uspreventiveservicestaskforce.org/uspstf05/brcagen/brcagenrs.htm .
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Breast Cancer Mammography Mastectomy