Potential of genetics in identifying women at lower risk of breast cancer: retrospective case-control study

In clinical practice, genetic information is not being used to identify women at lower risk of breast cancer who might start screening at higher age. A case-control study among women sequenced in the Healthy Nevada Project (2018-2022) investigated breast cancer incidence and age of onset among women with average genetic risk risk and women with low genetic risk (absence of pathogenic/likely pathogenic variants in BRCA1, BRCA2, PALB2, ATM, or CHEK2, and bottom 10% of polygenic risk score using a 313-single-nucleotide variant model). Among 25,591 women, 2338 (9.1%) were classified as having low genetic risk for breast cancer. This group exhibited significantly later onset of breast cancer compared with average-risk counterparts. By 45 years of age, 0.69% of those in the average-risk group were diagnosed with breast cancer, whereas those in the low-risk group reached this rate at age 51 years. By 50 years of age 1.41% of those in the average risk group were diagnosed with breast cancer, whereas those in the low-risk group reached this rate at age 58 years. The authors conclude that these results show a potential to defer mammogram screening by 5 to 10 years.