Article

Prediction of BRCA Mutations Using the BRCAPRO Model in Clinic-Based African American, Hispanic, and Other Minority Families in the United States

Department of Epidemiology, Columbia University, New York, New York, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 03/2009; 27(8):1184-90. DOI: 10.1200/JCO.2008.17.5869
Source: PubMed

ABSTRACT

BRCAPRO, a BRCA mutation carrier prediction model, was developed on the basis of studies in individuals of Ashkenazi Jewish and European ancestry. We evaluated the performance of the BRCAPRO model among clinic-based minority families. We also assessed the clinical utility of mutation status of probands (the first individual tested in a family) in the recommendation of BRCA mutation testing for other at-risk family members.
A total of 292 minority families with at least one member who was tested for BRCA mutations were identified through the Breast Cancer Family Registry and the University of Chicago. Using the BRCAPRO model, the predicted likelihood of carrying BRCA mutations was generated. Area under the receiver operating characteristic curves (AUCs) were calculated.
There were 104 African American, 130 Hispanic, 37 Asian-American, and 21 other minority families. The AUC was 0.748 (95% CI, 0.672 to 0.823) for all minorities combined. There was a statistically nonsignificant trend for BRCAPRO to perform better in Hispanic families than in other minority families. After taking into account the mutation status of probands, BRCAPRO performance in additional tested family members was improved: the AUC increased from 0.760 to 0.902.
The findings support the use of BRCAPRO in pretest BRCA mutation prediction among minority families in clinical settings, but there is room for improvement in ethnic groups other than Hispanics. Knowledge of the mutation status of the proband provides additional predictive value, which may guide genetic counselors in recommending BRCA testing of additional relatives when a proband has tested negative.

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    • "We also found better performance for IBIS in almost all covariate-specific subgroups, except for Hispanic and nonwhite women, and women with a prior breast biopsy. Race is an important predictor of breast cancer risk [36], and hereditary patterns and mutation prevalences differ by race and ethnicity [37]. The BCRAT model was updated, in 2008, to incorporate revised estimates for African American women [8] and in 2011, to include projections for Asian and Pacific Islander Americans. "
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    • "A larger cohort of male probands is necessary to allow further confirmation of our studies’ findings. Consistent with previous reported studies, we found that both BOADCIEA and BRCAPRO models underestimated the number of mutations carriers at a lower threshold and overestimated at a higher threshold [53]. "
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