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William J. Gradishar, MD, FACP, FASCO


Predicting a Woman’s Likelihood of Developing Breast Cancer: Focus on Polygenic Risk Scores

By: Victoria Kuhr, MS
Posted: Thursday, May 16, 2024

Nina Mars, MD, PhD, of the Institute for Molecular Medicine Finland, Helsinki, and colleagues reported that breast cancer polygenic risk scores may predict the outcome of an initial positive finding during screening. Additionally, researchers observed the effectiveness of a breast cancer polygenic risk score for risk stratification, when analyzed alone and combined with family history and pathogenic variants. These findings were published in the Journal of Clinical Oncology.

“The findings support the use of a breast cancer polygenic risk scores for risk stratification, with optimal stratification reached through combining polygenic risk scores information with family history of breast cancer and pathogenic variants in breast cancer susceptibility genes,” said the study authors.

The study evaluated polygenic risk scores, family history, and pathogenic variants for stratified screening. The study used FinnGen (n = 117,252), linked to the Mass Screening Registry for breast cancer with criteria between 1992 and 2019 from nationwide organized biennial screening for ages 50 to 69 years. The primary objectives were assessing the screening performance of a breast cancer polygenic risk score and comparing its performance with family history of breast cancer and pathogenic variants in moderate- (CHEK2) to high-risk (PALB2) susceptibility genes.

The study included 117,252 women from the Mass Screening Registry. The effect sizes for family history, pathogenic variants, and polygenic risk scores (above the 90th percentile) were comparable in screening-aged women, with similar implications for shifting age at screening onset. A high polygenic risk score identified women more likely to be diagnosed with breast cancer after a positive screening finding (positive predictive value of 39.5%). Combinations of risk factors increased the polygenic risk scores up to 45% to 50%. A high polygenic risk score conferred an elevated risk of interval breast cancer, and women with a low polygenic risk score (below the 10th percentile) had a low risk for both interval- and screen-detected breast cancers.

Disclosure: Dr. Mars reported no conflicts of interest. For full disclosures of the other study authors, visit

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