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Comment
. 2021 Apr;30(4):600-607.
doi: 10.1158/1055-9965.EPI-20-0900. Epub 2020 Dec 4.

Simplified Breast Risk Tool Integrating Questionnaire Risk Factors, Mammographic Density, and Polygenic Risk Score: Development and Validation

Bernard Rosner  1   2 , Rulla M Tamimi  3   4   5 , Peter Kraft  5   6 , Chi Gao  6 , Yi Mu  3 , Christopher Scott  7 , Stacey J Winham  7 , Celine M Vachon  8 , Graham A Colditz  9
Affiliations
Comment

Simplified Breast Risk Tool Integrating Questionnaire Risk Factors, Mammographic Density, and Polygenic Risk Score: Development and Validation

Bernard Rosner et al. Cancer Epidemiol Biomarkers Prev. 2021 Apr.

Abstract

Background: Clinical use of breast cancer risk prediction requires simplified models. We evaluate a simplified version of the validated Rosner-Colditz model and add percent mammographic density (MD) and polygenic risk score (PRS), to assess performance from ages 45-74. We validate using the Mayo Mammography Health Study (MMHS).

Methods: We derived the model in the Nurses' Health Study (NHS) based on: MD, 77 SNP PRS and a questionnaire score (QS; lifestyle and reproductive factors). A total of 2,799 invasive breast cancer cases were diagnosed from 1990-2000. MD (using Cumulus software) and PRS were assessed in a nested case-control study. We assess model performance using this case-control dataset and evaluate 10-year absolute breast cancer risk. The prospective MMHS validation dataset includes 21.8% of women age <50, and 434 incident cases identified over 10 years of follow-up.

Results: In the NHS, MD has the highest odds ratio (OR) for 10-year risk prediction: ORper SD = 1.48 [95% confidence interval (CI): 1.31-1.68], followed by PRS, ORper SD = 1.37 (95% CI: 1.21-1.55) and QS, ORper SD = 1.25 (95% CI: 1.11-1.41). In MMHS, the AUC adjusted for age + MD + QS 0.650; for age + MD + QS + PRS 0.687, and the NRI was 6% in cases and 16% in controls.

Conclusion: A simplified assessment of QS, MD, and PRS performs consistently to discriminate those at high 10-year breast cancer risk.

Impact: This simplified model provides accurate estimation of 10-year risk of invasive breast cancer that can be used in a clinical setting to identify women who may benefit from chemopreventive intervention.See related commentary by Tehranifar et al., p. 587.

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Conflict of interest statement

Conflict of interest

No conflicts are present for any author.

Figures

Figure 1
Figure 1
shows estimated 10-year incidence of breast cancer by case/control status Figure 1a contains a histogram of estimated 10-year breast cancer incidence in the NHS, separately for cases (blue) and controls (red). Figure 1b contains a histogram of estimated 10-year breast cancer incidence in the MMHS, separately for cases (blue) and controls (red).
See this image and copyright information in PMC

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