Considerations When Using Breast Cancer Risk Models for Women with Negative BRCA1/BRCA2 Mutation Results

Robert J. Macinnis, Yuyan Liao, Julia A. Knight, Roger L. Milne, Alice S. Whittemore, Wendy K. Chung, Nicole Leoce, Richard Buchsbaum, Nur Zeinomar, Gillian S. Dite, Melissa C. Southey, David Goldgar, Graham G. Giles, Sue Anne McLachlan, Prue C. Weideman, Stephanie Nesci, Michael L. Friedlander, Gord Glendon, Irene L. Andrulis, Esther M. JohnMary B. Daly, Saundra S. Buys, Kelly Anne Phillips, John L. Hopper, Mary Beth Terry

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Abstract

The performance of breast cancer risk models for women with a family history but negative BRCA1 and/or BRCA2 mutation test results is uncertain. We calculated the cumulative 10-year invasive breast cancer risk at cohort entry for 14 657 unaffected women (96.1% had an affected relative) not known to carry BRCA1 or BRCA2 mutations at baseline using three pedigree-based models (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, BRCAPRO, and International Breast Cancer Intervention Study). During follow-up, 482 women were diagnosed with invasive breast cancer. Mutation testing was conducted independent of incident cancers. All models underpredicted risk by 26.3%-56.7% for women who tested negative but whose relatives had not been tested (n = 1363; 63 breast cancers). Although replication studies with larger sample sizes are needed, until these models are recalibrated for women who test negative and have no relatives tested, caution should be used when considering changing the breast cancer risk management intensity of such women based on risk estimates from these models.

Original languageEnglish
Article numberdjz194
Pages (from-to)418-422
Number of pages5
JournalJournal of the National Cancer Institute
Volume112
Issue number4
DOIs
Publication statusPublished - 1 Apr 2020

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