Risk of Late-Onset Breast Cancer in Genetically Predisposed Women

Nicholas J. Boddicker, Chunling Hu, Jeffrey N. Weitzel, Peter Kraft, Katherine L. Nathanson, David E. Goldgar, Jie Na, Hongyan Huang, Rohan D. Gnanaolivu, Nicole Larson, Amal Yussuf, Song Yao, Celine M. Vachon, Amy Trentham-Dietz, Lauren Teras, Jack A. Taylor, Christopher E. Scott, Dale P. Sandler, Tina Pesaran, Alpa V. PatelJulie R. Palmer, Irene M. Ong, Janet E. Olson, Katie O’Brien, Susan Neuhausen, Elena Martinez, Huiyan Ma, Sara Lindstrom, Loic Le Marchand, Charles Kooperberg, Rachid Karam, David J. Hunter, James M. Hodge, Christopher Haiman, Mia M. Gaudet, Chi Gao, Holly LaDuca, James V. Lacey, Jill S. Dolinsky, Elizabeth Chao, Brian D. Carter, Elizabeth S. Burnside, Kimberly A. Bertrand, Leslie Bernstein, Paul W. Auer, Christine Ambrosone, Siddhartha Yadav, Steven N. Hart, Eric C. Polley, Susan M. Domchek, Fergus J. Couch

Research output: Contribution to journalArticlepeer-review


PURPOSE The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women in the general population over age 65 years is not well-defined. However, testing guidelines suggest that women diagnosed with breast cancer over age 65 years might have, 2.5% likelihood of a PV in a high-penetrance gene. This study aimed to establish the frequency of PVs and remaining risks of breast cancer for each gene in women over age 65 years. METHODS A total of 26,707 women over age 65 years from population-based studies (51.5% with breast cancer and 48.5% unaffected) were tested for PVs in germline predisposition gene. Frequencies of PVs and associations between PVs in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with PVs. RESULTS The frequency of PVs in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years. PVs in BRCA1, BRCA2, and PALB2 were found in 3.42% of women diagnosed with estrogen receptor (ER)–negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer. Frequencies of PVs were lower among women with no first-degree relatives with breast cancer. PVs in CHEK2, PALB2, BRCA2, and BRCA1 were associated with increased risks (odds ratio 5 2.9-4.0) of breast cancer. Remaining lifetime risks of breast cancer were $ 15% for those with PVs in BRCA1, BRCA2, and PALB2. CONCLUSION This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with BRCA1 and BRCA2 PVs and perhaps with PALB2 and CHEK2 PVs should be considered for magnetic resonance imaging screening.

Original languageEnglish (US)
Pages (from-to)3430-3440
Number of pages11
JournalJournal of Clinical Oncology
Issue number31
StatePublished - Nov 1 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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