Pathogenic Variants, Family History, and Cumulative Risk of Breast Cancer in US Women

作者：Katie M. O’Brien, Alexander P. Keil, Jack A. Taylor, Clarice Ring Weinberg, Eric C. Polley, Siddhartha Yadav, Nicholas James Boddicker, Chunling Hu, Christine B. Ambrosone, Hoda Anton Culver, Paul Livermore Auer, Clara Bodelón, Kristen D. Brantley, Elizabeth S. Burnside, Fei Chen, Susan M. Domchek, A. Heather Eliassen, Christopher A. Haiman, James M. Hodge, Peter Kraft, James Vincent Lacey, Sara Lindströem, Maria Elena Martinez, Katherine L. Nathanson, Susan L. Neuhausen, Janet E. Olson, Julie R. Palmer, Alpa V. Patel, Kathryn L. Penney, Kathryn J. Ruddy, Christopher G. Scott, Lauren R. Teras, Amy Trentham‐Dietz, Celine M. Vachon, Jeffrey N. Weitzel, Song Yao, Gary Zirpoli, Fergus J. Couch, Dale P. Sandler · 发表于：JAMA Oncology · 年份：2025 · DOI：10.1001/jamaoncol.2025.3875 · 被引用次数：8 · 研究领域：BRCA gene mutations in cancer、Breast Cancer Treatment Studies、Genetic factors in colorectal cancer

Importance: Inherited pathogenic variants (PVs) in known predisposition genes can greatly increase breast cancer risk, but the combined impact of PV status, family history, and other factors on breast cancer risk in the general US population has not been well described. Objective: To evaluate population-based breast cancer risk estimates for those with established PVs overall and stratified by first-degree family history of breast cancer and other factors. Design, Setting, and Participants: This study used pooled data from 13 US-based breast cancer case-control studies participating in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Enrollment for individual studies occurred between 1976 and 2013, and results are based on data released March 2023, with analyses conducted from June 2022 to July 2025. Exposures: PVs, breast cancer family history, self-reported race and ethnicity, and established risk factors. Main Outcomes and Measures: Breast cancer rate ratios for PVs in 7 genes were estimated from the CARRIERS consortium. PV status and incidence and mortality statistics were combined using the Individualized Coherent Absolute Risk Estimation (iCARE) model to estimate conditional cumulative breast cancer risks and 95% CIs, stratified by family history and standardized to the US population. Models that incorporated population-based data and published estimates for established epidemiologic risk factors were also evaluated. Results: A total of 67 692 ...