Personalizing Breast Cancer Screening Based on Polygenic Risk and Family History

Background: We assessed the clinical utility of a first-degree breast cancer family history and polygenic risk score (PRS) to inform screening decisions among women aged 30-50 years.
Methods: Two established breast cancer models evaluated digital mammography screening strategies in the 1985 US birth cohort by risk groups defined by family history and PRS based on 313 single nucleotide polymorphisms. Strategies varied in initiation age and interval. The benefits and harms were compared with those seen with 3 established screening guidelines.
Results: Women with a breast cancer family history who initiated biennial screening at age 40 years had a 36% increase in life-years gained and 20% more breast cancer deaths averted, but 21% more overdiagnoses and 63% more false positives. Screening tailored to PRS vs biennial screening from50 to 74 years had smaller positive effects on life-years gained and breast cancer deaths averted but also smaller increases in overdiagnoses and false positives. Combined use of family history and PRS vs biennial screening from 50 to 74 years had the greatest increase in life-years gained and breast cancer deaths averted.
Conclusions: Our results suggest that breast cancer family history and PRS could guide screening decisions before age 50 years among women at increased risk for breast cancer but expected increases in overdiagnoses and false positives should be expected.