Genetic Identification of Women at Lower Risk of Breast Cancer

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In a retrospective analysis reported in JAMA Oncology, Bolze et al identified a group of women at low risk for breast cancer based on genetic analysis. The findings may support altering cancer screening in this low-risk group.

As stated by the investigators, “Genetic information is not being used to identify women at lower risk of breast cancer or other diseases in clinical practice. With the new U.S. Preventive Services Task Force guidelines lowering the age for mammogram screening for all, there is a potential benefit in identifying women at lower risk of disease who may defer the start of mammographic screening. This genetic risk-based approach would help mitigate overscreening, associated costs, and anxiety.”

Study Details

The study involved 25,591 women from the Healthy Nevada Project who were sequenced by Helix between 2018 and 2022. Inclusion in the low-risk genetic group required: (1) absence of pathogenic variants or a variant of uncertain significance in BRCA1, BRCA2, PALB2, ATM, or CHEK2; and (2) a low polygenic risk score (bottom 10%) using a 313-single-nucleotide variant model.

Key Findings

Among the 25,591 women in the analysis, 2,338 (9.1%) were classified as low risk; 410 (1.6%) as high risk; and 22,843 (89.3%) as average risk. Overall, women with low risk had a significantly reduced risk of cancer diagnosis vs women with average risk (hazard ratio [HR] = 0.39, 95% confidence interval [CI] = 0.29–0.52, P < .001).

By age 45, 0.69% of women in the average-risk group were diagnosed with breast cancer, whereas women in the low-risk group reached this rate at age 51. By age 50, 1.41% of women in the average-risk group were diagnosed with breast cancer, whereas those in the low-risk group reached this rate at age 58.

In particular, significant differences in diagnosis of breast cancer in the low-risk vs average-risk group were observed at age 50 (1.41% vs 0.60 %, HR = 0.48, 95% CI = 0.26–0.91), age 55 (2.62% vs 0.99%, HR = 0.40, 95% CI = 0.24–0.66), age 60 (4.30% vs 2.03%, HR = 0.47, 95% CI = 0.32–0.70), age 65 (6.70% vs 2.95%, HR = 0.46, 95% CI = 0.32–0.64). and age 70 (9.90% vs 3.65%, HR = 0.40, 95% CI = 0.29–0.55).

As noted by the investigators, “These findings suggest that deferring mammogram screening by 5 to 10 years for women at low risk of breast cancer aligns with new draft recommendations.”

They concluded, “The findings of this retrospective case-control study underscore the value of genetics in individualizing the onset of breast cancer screening. Improving breast cancer risk stratification by implementing both high-risk and low-risk strategies in screening can refine preventive measures and optimize health-care resource allocation.”

Alexandre Bolze, PhD, of Helix, San Mateo, CA, is the corresponding author for the JAMA Oncology article.   

Disclosure: The study was funded by the Desert Research Institute (through the Nevada Governor’s Office of Economic Development), Renown Health, and the Renown Health Foundation. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.