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Results of a large study on genetic predisposition suggest that women diagnosed with triple-negative breast cancer or estrogen receptor-negative breast cancer should receive genetic testing and women over age 65 with other pathogenic variants should be considered for magnetic resonance imaging screening.

Current National Comprehensive Cancer Network guidelines suggest that hereditary cancer testing for women with breast cancer diagnosed at age 65+ has limited clinical utility without specific risk factors, such as Ashkenazi Jewish ancestry or a family history of cancer. However, few studies have specifically evaluated predisposition genes in women over 65.

Nicholas J. Boddicker, PhD, of the Mayo Clinic in Rochester, Minnesota, and colleagues therefore set out to determine the prevalence of pathogenic variants in established breast cancer predisposition genes and estimate the remaining lifetime risks of breast cancer associated with pathogenic variants among women over age 65 in the general population.

As noted in the team's study in the , a total of 26,707 women over age 65 from population-based research (51.5% with breast cancer and 48.5% unaffected) were tested for pathogenic variants in germline predisposition gene.

In the following interview, Boddicker elaborated on the findings.

What does your study add to the literature about the risk of late-onset breast cancer in genetically predisposed women?

Boddicker: This large study provides frequencies of pathogenic variants in breast cancer predisposition genes and breast cancer risk estimates for those with these pathogenic variants among women over age 65 years. Because older women have not previously been studied in any detail, the risk of breast cancer in this population was not well understood.

What are the highlights of the study?

Boddicker: Women over age 65 with pathogenic variants in BRCA1, BRCA2, and PALB2 are still at increased risk of breast cancer, with carriers of BRCA1 and BRCA2 pathogenic variants having nearly 20% remaining lifetime risk.

Additionally, women with estrogen receptor-negative breast cancer or triple-negative breast cancer diagnosed at later ages had a greater than 2.5% probability of carrying a pathogenic variant in BRCA1, BRCA2, and PALB2, the threshold necessary for genetic testing, suggesting that all women in this age category with these diagnoses should be offered clinical genetic testing.

Why are better estimates needed for remaining lifetime risk of breast cancer associated with pathogenic variants in women older than 65?

Boddicker: Remaining lifetime risk estimates are not well established for this older population. The added information on lifetime risk can inform better patient management, such as enhanced screening and perhaps prevention measures among older women.

Based on these results, which women should have MRI screening if they carry specific genes associated with breast cancer?

Boddicker: Women over age 65 with pathogenic variants in BRCA1 and BRCA2 have a remaining lifetime risk of nearly 20%, suggesting that they should have MRI screening. Furthermore, women with PALB2 and CHEK2 have an approximately 15% lifetime risk, and one could argue that these women could also benefit from MRI screening.

What is the bottom-line message for practicing oncologists?

Boddicker: The results from this study shed light on frequencies of pathogenic variants and risk of breast cancer in this understudied older population. Women with estrogen receptor-negative or triple-negative breast cancer have a probability of carrying a pathogenic variant in high-risk genes that qualify them for genetic testing. Women with pathogenic variants in key breast cancer predisposition genes continue to be at increased risk of breast cancer and MRI screening should be considered.

Read the study here.