Risk of Breast Cancer and Frequency of Pathogenic Variants in Older Women
Posted: Thursday, November 5, 2020
Women diagnosed with breast cancer after age 65 often do not qualify for genetic testing. However, according to Nicholas J. Boddicker, PhD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, the risk of breast cancer and the frequency of pathogenic variants are not negligible in this patient population. The results of this recent study were presented during the American Society of Human Genetics (ASHG) Virtual Meeting 2020 (Abstract 2412).
“In this study, women older than age 65 with no prior breast cancer found to have pathogenic variants in one of several genes would have a remaining risk of breast cancer nearing 20% and could qualify for MRI surveillance in addition to mammography,” Dr. Boddicker commented in an ASHG press release. “Without genetic testing, many of these women would not normally be screened this way.”
Using a custom multigene amplicon-based panel, the investigators sequenced germline DNA obtained from the CARRIERS consortium. A total of 13,762 women older than age 65 with breast cancer and 12,945 age-matched unaffected controls were included.
The frequency of pathogenic variants in 12 established breast cancer predisposition genes was 3.2% in patients with breast cancer and 1.5% in age-matched unaffected controls. The highest frequencies occurred in ATM (0.5%), BRCA1 (0.2%), BRCA2 (0.5%), CHEK2 (0.7%), and PALB2 (0.2%). The investigators identified four genes that seemed to be associated with a moderate risk of breast cancer: BRCA1, BRCA2, PALB2, and CHEK2. There did not appear to be a significant association between ATM and the risk of breast cancer (P = .086). For women between the ages of 66 and 85, the residual risk of breast cancer was 9.8% for ATM, 18.3% for BRCA1, 18.6% for BRCA2, 14.9% for CHEK2, and 15.8% for PALB2. In the general population, the residual risk of breast cancer was 6.8%.
Disclosure: Dr. Boddicker reported no conflicts of interest.
