Boddicker NJ, et al.

Risk of Late-Onset Breast Cancer in Genetically Predisposed Women.

J Clin Oncol. 2021 Jul 22;JCO2100531. doi: 10.1200/JCO.21.00531

The median age of breast cancer diagnosed in the general population is 62 years old. Hereditary breast cancer comprises about 10% of breast cancer diagnoses. This occurs when a patient inherits a mutation in a breast cancer predisposing gene. Hereditary breast cancer is associated with a younger age of diagnosis, a strong family history of breast and/or ovarian cancer, Ashkenazi Jewish ancestry, or estrogen receptor (ER)-negative breast cancer. Knowing that a patient has a mutation in a breast cancer predisposing gene can impact patient management. Patients may undergo increased surveillance imaging, such as with magnetic resonance imaging (MRI), or undergo risk-reducing prophylactic mastectomy. The National Comprehensive Cancer Network (NCCN) guidelines suggest that genetic testing for women over 65 years old may have limited utility unless they have the above risk factors. This recommendation is based on that women over 65 years old have a less than 2.5% chance of having a pathogenic variant in a breast cancer predisposing gene. Few studies have evaluated the frequency of inheriting a predisposition gene in women over 65 years old.

Boddicker et al. conducted the largest population-based study to date of women over 65 years old diagnosed with breast in the U.S. to evaluate the frequency of a breast cancer predisposing gene in women over 65 years old. 26,707 women were included in the study. 51.5% had breast cancer and 48.5% were unaffected (did not have breast cancer). The genes included in the analysis were ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, and TP53. The frequency of a pathogenic variant in a predisposition gene was 3.18% in women with breast cancer and 1.48% in unaffected women. Pathogenic variants in BRCA1, BRCA2, and PALB2 were found in 3.42% of women diagnosed with ER-negative breast cancer (vs. 1.0% in ER-positive) and 3.01% in women with triple negative breast cancer. Unaffected women who were carriers of BRCA1 and BRCA2 pathogenic variants had estimated remaining lifetime risks of breast cancer of 20% while women with PALB2 and CHEK2 carriers had 15% remaining lifetime risks. The study concluded that all women with triple negative or ER-negative breast cancer should undergo genetic testing. Furthermore, women over 65 years old with BRCA1 and BRCA2 pathogenic variants should undergo enhanced screening with MRI while women with PALB2 and CHEK2 pathogenic variants should consider enhanced screening.

Patients interested in genetic testing should discuss this with their doctor. The decision for testing will be based on personal and family history, as well as subtype of breast cancer. Those identified as high risk for breast cancer, including those with a pathogenic variant in a breast cancer predisposing gene should also discuss with their surgeon if they should receive enhance surveillance imaging with MRI and whether a risk-reducing prophylactic mastectomy should be performed. Boddicker et al. suggest that women over 65 years old should also be part of this conversation.