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PurposeThe 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.MethodsA 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.ResultsThe 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.ConclusionThis 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 publication

DOI

10.1200/jco.21.00531

Type

Journal article

Journal

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Publication Date

11/2021

Volume

39

Pages

3430 - 3440

Addresses

Mayo Clinic, Rochester, MN.

Keywords

Humans, Breast Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, BRCA2 Protein, Prognosis, Case-Control Studies, Follow-Up Studies, Age of Onset, Germ-Line Mutation, Aged, Aged, 80 and over, Female, Genetic Testing, Checkpoint Kinase 2, Biomarkers, Tumor, Fanconi Anemia Complementation Group N Protein