Validation of a tool for identifying women at high risk for hereditary breast cancer in population-based screening

Abstract

Background: Recent scientific advances provide the opportunity to identify women in the general population at increased breast cancer risk and to offer effective early detection and disease prevention interventions.

Methods: A pedigree assessment tool (PAT) was designed to identify women in primary care settings who are at increased risk for hereditary breast cancer, including potential BRCA mutation carriers. The PAT is a simple point-scoring system based on family cancer history with points weighted to account for features associated with a higher probability that a BRCA mutation is present. The ability of the PAT and the Gail model to accurately identify potential BRCA mutation carriers in 3,906 women without a personal history of breast cancer presenting for a screening mammogram at a community hospital was tested.

Results: Eighty-six (2.2%) women had a family history indicative of a high probability (>10%) that a BRCA mutation was present within the family. The PAT performed better than the Gail model in correctly assigning women to the "high BRCA probability" cohort. The area under the receiver operating characteristic (ROC) curve for the PAT was 0.9625 compared with 0.389 and 0.5861 for the Gail model 5-year and lifetime risk estimates, respectively. At the optimal threshold score, the PAT performed with 100% sensitivity and 93% specificity.

Conclusions: The PAT is a simple and accurate tool for identifying women at risk for the hereditary breast cancer syndromes that can be employed as part of a comprehensive breast cancer risk-screening strategy in the primary care setting.