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  5. Performance of an image-only deep learning breast cancer risk model with the addition of a polygenic risk score

Performance of an image-only deep learning breast cancer risk model with the addition of a polygenic risk score

File(s)
41942608.pdf (1.76 MB)
No Access Until
2026-10-06
Permanent Link(s)
https://hdl.handle.net/1813/126864
Collections
Department of Healthcare Policy & Research
Author
Azam, Shadi
Lamb, Leslie R.
Eliassen, A Heather
King, Tari A.
Specht, Michelle
Kraft, Peter
Lindstrom, Sara
Lehman, Constance D.
Tamimi, Rulla M.
Abstract

BACKGROUND: Mammograms contain imaging biomarkers that can predict future breast cancer risk using deep learning (DL) models. We evaluated whether adding a polygenic risk score (PRS) improves performance of the image-only DL breast cancer risk model Mirai. METHODS: This nested case-control study within the Nurses' Health Study 2 included 902 women (270 cases, 632 controls) who underwent bilateral 2D digital screening mammography between 2001-2017. Risk was assessed using Mirai and, for clinical comparison, the Gail 5-year model. A PRS was calculated using 313 breast cancer-associated single-nucleotide polymorphisms. The primary outcome was incident breast cancer within five years of the index mammogram. Discrimination was evaluated using area under the receiver operating characteristic curve (AUC), with comparisons using the DeLong test. RESULTS: Mean age was 55.5 years(SD 5.3). Among cases, median time from index mammogram to diagnosis was 2.0 years (IQR0.5-4.0). Mirai alone achieved an AUC of 0.66 (95% CI: 0.62-0.70), increasing to 0.73 (95% CI 0.67-0.78; P = 0.05) with PRS. The Gail model improved from 0.52 (95% CI: 0.47-0.57) to 0.69 (95% CI: 0.62-0.76; P < 0.001) with PRS. Mirai+PRS significantly outperformed Gail+PRS (P < 0.001). CONCLUSIONS: Integrating PRS with DL-based mammographic models modestly improves risk discrimination and may enhance personalized screening.

Journal / Series
British journal of cancer
Volume & Issue
134(11)
Date Issued
2026-04-06
Publisher
Springer
Keywords
WCM Library Coordinated Deposit
•
Humans
•
Female
•
Breast Neoplasms/genetics/diagnostic imaging/epidemiology
•
Genetic Risk Score
•
Middle Aged
•
Deep Learning
•
Case-Control Studies
•
Mammography/methods
•
Polymorphism, Single Nucleotide
•
Risk Factors
•
Early Detection of Cancer/methods
•
Risk Assessment
•
ROC Curve
•
Aged
•
Genetic Predisposition to Disease
Related DOI
https://doi.org/10.1038/s41416-026-03415-z
Previously Published as
Azam S, Lamb LR, Eliassen AH, King TA, Specht M, Kraft P, Lindstrom S, Lehman CD, Tamimi RM. Performance of an image-only deep learning breast cancer risk model with the addition of a polygenic risk score. British journal of cancer. 2026;134(11):1624-1632. doi: 10.1038/s41416-026-03415-z. PMID: 41942608.
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Rights URI
https://creativecommons.org/licenses/by-nc-nd/4.0/
Type
article

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