Risk of Breast Cancer Influenced by BRCA1/BRCA2 Mutations and Family History

Cancer


Women with genetic mutations in the BRCA1 and BRCA2 genes and 2 or more close relatives with breast cancer are almost twice as likely to develop breast cancer than those with no family history of the disease.

BRCA1 and BRCA2 are human genes that produce proteins involved in tumor suppression. Inherited mutations in BRCA1 and BRCA2 increase the risk of breast and ovarian cancers. Accurate age-specific cancer risk estimates are necessary for the best possible clinical care of women with BRCA1 and BRCA2 mutations.

A study by Karoline Kuchenbaecker and colleagues, published in the Journal of the American Medical Association, estimated age-specific breast and ovarian cancer risks from data collected through several long-term cancer studies. Data from a total of 3886 participants with BRCA1 and BRCA2 mutations were used for a breast cancer risk analysis. For ovarian cancer risk, data from 5066 participants were examined. The median age for both groups was 38 years at the beginning of the study. For BRCA1 carriers, the cumulative risk of breast cancer by age 80 was estimated at 72% (95% CI, 65%-79%). The result for BRCA2 carriers was similar, with an estimated risk of 75% (95% CI, 67%-83%) by age 80. However, the cumulative risks to age 50 years were higher for BRCA1 carriers (p = 0.03) than for BRCA2 carriers. The study also found an increased incidence of ovarian cancer in ages up to 61 to 70 for participants with BRCA1 or BRCA2 mutations. The cumulative risk of ovarian cancer to age 80 was higher for BRCA1 carriers (44%, 95% CI, 36%-53%) than for BRCA2 carriers (17%, 95% CI, 11%-25%).

Additionally, breast cancer risk estimates for women with either a BRCA1 or BRCA2 mutation increased as the number of first- and second-degree relatives diagnosed with breast cancer increased. Women with either mutation who had two or more first- or second-degree relatives diagnosed with breast cancer were almost twice as likely to develop breast cancer than those with no family history of the disease.

The results of this study highlight the importance of family history in cancer risk management and may help doctors provide better care for women with multiple breast and ovarian cancer risk factors.

Written By: Cindi A. Hoover, Ph.D.

Source: Kuchenbaecker K, Hopper JL, Barnes DR, Phillips K-A, Mooij TM, Roos-Blom M-J, Jervis S, van Leeuwen FE, Milne RL, Andrieu N, Goldgar DE, Terry MB, Rookus MA, Easton DF, Antoniou AC, and the BRCA1 and BRCA2 Cohort Consortium. 2017. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. Journal of the American Medical Association. 317:23:2402-2416.



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