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Age-specific overall risk of breast, ovarian cancer among women with BRCA1/2 genetic mutations

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Age-specific overall risk of breast, ovarian cancer among women with BRCA1/2 genetic mutations

Researchers conducted an analysis that included nearly 10,000 women with the BRCA1 or BRCA2 genetic mutations to estimate the age-specific risk of breast or ovarian cancer for women with these mutations, according to a study published by JAMA.

The optimal clinical management of women with BRCA1 and BRCA2 mutations depends on accurate age specific cancer risk estimates. These can be used to estimate the absolute risk reduction from preventive strategies and to inform decisions about the age at which to begin cancer screening. Antonis C. Antoniou, Ph.D., of the University of Cambridge, England, and colleagues included 6,036 BRCA1 and 3,820 BRCA2 female carriers (5,046 unaffected and 4,810 with breast or ovarian cancer or both at study entry) in the analysis.

During a median follow-up of 5 years, 426 women were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer (cancer in the breast opposite to one previously diagnosed with cancer). Among the findings of the researchers:

  • The cumulative breast cancer risk to age 80 years was 72 percent for BRCA1 and 69 percent for BRCA2 carriers.
  • Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence until age 80 years.
  • The cumulative ovarian cancer risk to age 80 years was 44 percent for BRCA1 and 17 percent for BRCA2 carriers.
  • For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40 percent for BRCA1 and 26 percent for BRCA2 carriers.
  • Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 and BRCA2 carriers.
  • Cancer risk varied by mutation location within the BRCAl or BRCA2 gene.

Limitations of the study include that although there was variation in the cancer risks for mutation carriers by cancer family history, the study sample was not identified through population screening of unaffected women; therefore, the overall estimates may not be directly applicable to such women.

"The results indicate that family history is a strong risk factor for mutation carriers and that cancer risks vary by mutation location, suggesting that individualized counseling should incorporate both family history profiles and mutation location," the authors write.

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