Screen-positive rates and agreement among six family history screening protocols for breast/ovarian cancer in a population-based cohort of 21- to 55-year-old women

Abstract

Purpose: Mutations in the BRCA1 and BRCA2 genes are responsible for approximately 2% of breast cancers by age 70 years. Professional and governmental groups recommend using family history protocols as an initial step in identifying women and families for mutation testing. We assess screen-positive rates and levels of agreement between these protocols. Methods: We applied six family history screening protocols to a population-based cohort of 321 women, age 21 to 55 years, who reported their personal and family history of breast and ovarian cancer. Results: The proportion of women and families identified as candidates for mutation testing ranged from 4.4% to 7.8%, depending on the protocol. The protocols had low or fair agreement (kappa <0.75 for 14 of 15 comparisons), but all identified six women (1.9%, 95% confidence interval 0.7%-4.0%) as screen positive. When the effect of missing ages of cancer onset was modeled, these rates increased (range 6.5%-11.5%), and nine women (2.8%) were screen positive by all protocols. Conclusion: Given limitations of family history as a screening test for hereditary cancer related to BRCA1/2 mutations, 1% to 2% of women in the general population should initially be identified for mutation testing. One way to achieve this would be to require that multiple screening protocols agree. Copyright © American College of Medical Genetics.