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

Genet Med. 2006 Mar;8(3):161-8. doi: 10.1097/01.gim.0000204458.84988.f2.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age of Onset
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Cohort Studies
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Testing / methods*
  • Germ-Line Mutation
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / genetics*
  • Pedigree*
  • Population Surveillance*
  • Risk Factors
  • United States / epidemiology