Incidence Of Cancer In BRCA1/2 Carriers Is Increasing

April 2017

Cancer

Country of origin: UK

The identification of a BRCA1 or BRCA2 mutation in familial breast cancer kindreds allows genetic testing of at risk relatives. However, considerable controversy exists regarding the cancer risks in women who test positive for the family mutation.

Researchers reviewed 385 unrelated families (223 with BRCA1 and 162 with BRCA2 mutations) ascertained through two regional cancer genetics services. They estimated the penetrance for both breast and ovarian cancer in female mutation carriers (904 proven mutation carriers ? 1442 females in total assumed to carry the mutation) and also assessed the effect on penetrance of mutation position and birth cohort.

Breast cancer penetrance to 70 and to 80 years was 68% (95%CI 64.7?71.3%) and 79.5% (95%CI 75.5?83.5%) respectively for BRCA1 and 75% (95%CI 71.7?78.3%) and 88% (95%CI 85.3?91.7%) for BRCA2. Ovarian cancer risk to 70 and to 80 years was 60% (95%CI 65?71%) and 65% (95%CI 75?84%) for BRCA1 and 30% (95%CI 25.5?34.5%) and 37% (95%CI 31.5?42.5%) for BRCA2. These risks were borne out by a prospective study of cancer in the families and genetic testing of unaffected relatives. They also found evidence of a strong cohort effect with women born after 1940 having a cumulative risk of 22% for breast cancer by 40 years of age compared to 8% in women born before 1930 (p = 0.0005).

The research concludes that in high-risk families, selected in a genetics service setting, women who test positive for the familial BRCA1/BRCA2 mutation are likely to have cumulative breast cancer risks in keeping with the estimates obtained originally from large families. This is particularly true for women born after 1940.

The full research article is available online.

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