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