Personalizing Breast Cancer Screening Based on Polygenic Risk and Family History

Jeroen J. Van Den Broek*, Clyde B. Schechter, Nicolien T. Van Ravesteyn, A. Cecile J.W. Janssens, Michael C. Wolfson, Amy Trentham-Dietz, Jacques Simard, Douglas F. Easton, Jeanne S. Mandelblatt, Peter Kraft, Harry J. De Koning

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

33 Citations (Scopus)
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Abstract

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 (30, 35, 40, 45, and 50 years) and interval (annual, hybrid, biennial, triennial). The benefits (breast cancer deaths averted, life-years gained) and harms (false-positive mammograms, overdiagnoses) 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 (vs 50 years) had a 36% (model range = 29%-40%) increase in life-years gained 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 screening from 50 to 74 years had smaller positive effects on life-years gained (20%) and breast cancer deaths averted (11%) but also smaller increases in overdiagnoses (10%) and false positives (26%). Combined use of family history and PRS vs biennial screening from 50 to 74 years had the greatest increase in life-years gained (29%) and breast cancer deaths averted (18%). 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.

Original languageEnglish
Pages (from-to)434-442
Number of pages9
JournalJournal of the National Cancer Institute
Volume113
Issue number4
DOIs
Publication statusPublished - 1 Apr 2021

Bibliographical note

Funding Information:
This research was supported by the National Institutes of Health under National Cancer Institute (NCI) Grants U01CA12958 and U01CA199218. Collection of Breast Cancer Surveillance Consortium (BCSC) data used in this study was supported by National Cancer Institute-funded grants P01CA154292 and U54CA163303 and contract HHSN261201100031C.

Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press.

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