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Women Over Age 65 Years with Pathogenic Variants in Cancer Predisposition Genes Continue to Be at Increased Risk of Breast Cancer

Women in this age category qualify for clinical genetic testing and magnetic resonance imaging screening
27 Jul 2021
Cancer in Older Adults;  Cancer Prevention;  Pathology/Molecular Biology
Breast Cancer

Women over age 65 years with pathogenic variants in cancer predisposition genes rarely benefit from hereditary cancer genetic testing. A population-based study examined whether women in this age category may qualify for clinical genetic testing and magnetic resonance imaging (MRI) screening. The US researchers led by Dr Fergus Couch of the Mayo Clinic in Rochester, MN wrote on 22 July 2021 in the Journal of Clinical Oncology that all women diagnosed with triple-negative breast cancer (TNBC) or oestrogen receptor (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 MRI screening.

Hereditary breast cancer is associated with a younger age of diagnosis, strong family history of breast and/or ovarian cancer, Ashkenazi Jewish ancestry, or ER–negative breast cancer. In these high-risk women, the chance of observing a pathogenic variant in a cancer predisposition gene is approximately 10%. Knowing predisposition gene pathogenic variant status can have a profound impact on patient management through enhanced screening for breast and other cancers, access to risk-reducing prophylactic surgeries, and targeted treatment for breast, ovarian, and other cancers.

The goal of the current study was to determine the prevalence of pathogenic variants in established breast cancer predisposition genes and to estimate remaining lifetime risks of breast cancer associated with pathogenic variants among women over age 65 years in the general population.

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 pathogenic variants in germline predisposition gene. Frequencies of pathogenic variants and associations between pathogenic variants in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with pathogenic variants.

The frequency of pathogenic variants in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years.

Pathogenic variants in BRCA1, BRCA2, and PALB2 were found in 3.42% of women diagnosed with ER–negative, 1.0% with ER-positive, and 3.01% with TNBC.

Frequencies of pathogenic variants were lower among women with no first-degree relatives with breast cancer.

Pathogenic variants 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 pathogenic variants in BRCA1, BRCA2, and PALB2.

The study authors commented that their results will inform cancer screening guidelines and risk management for women over age 65 years in the general population, especially for those with TNBC diagnosed over age 60 years or ER-negative disease diagnosed over age 65 years. Women over age 65 years with pathogenic variants in BRCA1, BRCA2, CHEK2, and PALB2 continue to be at increased risk of breast cancer, with remaining lifetime risks approaching 20%. Therefore, MRI screening should be considered for those with pathogenic variants in BRCA1 and BRCA2 and might be considered for those with pathogenic variants in PALB2 and CHEK2.

The study was supported by the US National Institute of Health (NIH) grants, an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer, and the Breast Cancer Research Foundation.

Reference

Boddicker NJ, Hu C, Weitzel JN, et al. Risk of Late-Onset Breast Cancer in Genetically Predisposed Women. JCO; Published online 22 July 2021. DOI: 10.1200/JCO.21.00531.

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