Personalizing Breast Cancer Screening Based on Polygenic Risk and Family History

Affiliations

PMID: 32853342
DOI: 10.1093/jnci/djaa127

Abstract

Background: We assessed the clinical utility of a first-degree breast cancer family history (FH) and polygenic risk score (PRS) to inform screening decisions among women aged 30-50 years.

Method: Two established breast cancer models evaluated digital mammography screening strategies in the 1985 US birth cohort by risk groups defined by family history and polygenic risk score (PRS) based on 313-single nucleotide polymorphism. Strategies varied in initiation age (30, 35, 40, 45, 50) and interval (annual, hybrid, biennial [B], triennial). The benefits, breast cancer deaths averted, life years gained (LYG) and harms, false-positive (FP) mammograms, overdiagnoses, were compared those seen with three established screening guidelines.

Results: Women with a breast cancer FH who initiate biennial screening at age 40 years (vs. 50) had a 36% (model range: 29%-40%) increase in LYG and 20% (model range: 16%-24%) more breast cancer deaths averted, but 21% (model range: 17%-23%) more overdiagnoses and 63% (model range: 62%-64%) more false positives. Screening tailored to PRS vs. biennial 50-74 screening had smaller positive effects on LYG (20%) and breast cancer deaths averted (11%) but also smaller increases in overdiagnoses (10%) and false positives (26%). Combined use of FH and PRS vs. B50-74 had the greatest increase in LYG (29%) and breast cancer deaths averted (18%).

Conclusion: Our results suggest that breast cancer family history and polygenic risk could guide screening decisions before age 50 years among women at increased risk for breast cancer, but should consider expected increases in overdiagnoses and false positives.

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