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000306202 1001_ $$00000-0002-3017-4023$$aHo, Peh Joo$$b0
000306202 245__ $$aThreshold-Based Overlap of Breast Cancer High-Risk Classification Using Family History, Polygenic Risk Scores, and Traditional Risk Models in 180,398 Women.
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000306202 520__ $$aBackground: Breast cancer polygenic risk scores (PRS) and traditional risk models (e.g., the Gail model [Gail]) are known to contribute largely independent information, but it is unclear how the overlap varies by ancestry, age, disease type (invasive breast cancer, DCIS), and risk threshold. Methods: In a retrospective case-control study, we evaluated risk prediction performance in 180,398 women (161,849 of European ancestry; 18,549 of Asian ancestry). Odds ratios (ORs) from logistic regression models and the area under the receiver operating characteristic curve (AUC) were estimated. Results: PRS for invasive disease showed a stronger association in younger (<50 years) women (OR = 2.51, AUC = 0.622) than in women ≥ 50 years (OR = 2.06, AUC = 0.653) of European ancestry. PRS performance in Asians was lower (OR range = 1.62-1.64, AUC = 0.551-0.600). Gail performance was modest across groups and poor in younger Asian women (OR = 0.94-0.99, AUC = 0.523-0.533). Age interactions were observed for both PRS (p < 0.001) and Gail (p < 0.001) in Europeans, whereas in Asians, age interaction was observed only for Gail (invasive: p < 0.001; DCIS: p = 0.002). PRS identified more high-risk individuals than Gail in Asian populations, especially ≥50 years, while Gail identified more in Europeans. Overlap between PRS, Gail, and family history was limited at higher thresholds. Calibration analysis, comparing empirical and model-based ROC curves, showed divergence for both PRS and Gail (p < 0.001), which indicates miscalibration. In Europeans, family history and prior biopsies drove Gail discrimination. In younger Asians, age at first live birth was influential. Conclusions: PRS adds value to risk stratification beyond traditional tools, especially in younger women and Asian ancestry populations.
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000306202 650_7 $$2Other$$aBRCA1
000306202 650_7 $$2Other$$aBRCA2
000306202 650_7 $$2Other$$aGail model
000306202 650_7 $$2Other$$abreast cancer
000306202 650_7 $$2Other$$aductal carcinoma in situ (DCIS)
000306202 650_7 $$2Other$$apolygenic risk score (PRS)
000306202 650_7 $$2Other$$arisk stratification
000306202 650_7 $$2Other$$arisk-based screening
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000306202 7001_ $$00000-0003-0771-7752$$aAhearn, Thomas U$$b5
000306202 7001_ $$00000-0002-4226-6435$$aAndrulis, Irene L$$b6
000306202 7001_ $$aAntonenkova, Natalia N$$b7
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000306202 7001_ $$00000-0002-9736-4593$$aBogdanova, Natalia V$$b12
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