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Risk of Breast Cancer in Women Older Than Age 65 With Germline Pathogenic Variants in Predisposition Genes


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In a study reported in the Journal of Clinical Oncology, Boddicker et al found that women older than age 65 in the general population who carry germline pathogenic variants in established high-risk breast cancer predisposition genes remain at significant risk of late-onset breast cancer and should be considered for magnetic resonance imaging screening.

Study Details

The study involved data from 26,707 women aged > 65 years from population-based studies who were tested for pathogenic variants in germline predisposition genes. The cohort consisted of 13,762 women with breast cancer and 12,945 study- and age-matched unaffected controls. Frequencies of pathogenic variants and associations of pathogenic variants with breast cancer were assessed. Absolute risk of breast cancer from age 66 to 85 years was calculated for non-Hispanic White carriers of pathogenic variants by combining gene-specific odds ratios with age-specific breast cancer incidence rates for non-Hispanic White women from the Surveillance, Epidemiology, and End Results-21 (SEER-21) program. Analysis was limited to White women (83% of the entire cohort) due to the low number of pathogenic variants found in other racial/ethnic groups.

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 pathogenic variants, and perhaps with PALB2 and CHEK2 pathogenic variants, should be considered for magnetic resonance imaging screening.
— Boddicker et al

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Key Findings

The frequency of 12 established predisposition genes was 3.18% among breast cancer cases and 1.48% among controls. For cases vs controls, proportions with pathogenic variants were 0.28% vs 0.07% for BRCA1, 0.71% vs 0.26% for BRCA2, 0.36% vs 0.10% for PALB2, and 0.92% vs 0.39% for CHEK2.  

Pathogenic variants in BRCA1, BRCA2, or PALB2 were found in 3.42% of women with estrogen receptor (ER)-negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer.

Pathogenic variants in the 12 predisposition genes were identified in 4.5% of women with breast cancer and a first-degree relative with breast cancer (2.3% in BRCA1, BRCA2, or PALB2) and in 2.7% without family history (1.0% in BRCA1, BRCA2, or PALB2).

Pathogenic variants in CHEK2 (odds ratio [OR] = 2.13), PALB2 (OR = 3.09), BRCA2 (OR = 2.64), and BRCA1 (OR = 3.37) were associated with increased risk of breast cancer.  

The absolute risk of breast cancer in the general population on the basis of SEER-21 incidence rates from 66 to 85 years was 6.8%. Among White controls with pathogenic variants in the current study, the remaining lifetime risk from age 66 to 85 years was estimated at 18.4% for BRCA1, 18.7% for BRCA2, 15.9% for PALB2, and 14.9% for CHEK2.

The investigators concluded, “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 pathogenic variants, and perhaps with PALB2 and CHEK2 pathogenic variants, should be considered for magnetic resonance imaging screening.”

Fergus J. Couch, PhD, of the Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Institutes of Health and the Breast Cancer Research Foundation. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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