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@ARTICLE{Hurson:168129,
author = {A. N. Hurson and P. Pal Choudhury and C. Gao and A.
Hüsing$^*$ and M. Eriksson and M. Shi and M. E. Jones and
D. G. R. Evans and R. L. Milne and M. M. Gaudet and C. M.
Vachon and D. I. Chasman and D. F. Easton and M. K. Schmidt
and P. Kraft and M. Garcia-Closas and N. Chatterjee},
collaboration = {B. R. M. Group},
title = {{P}rospective evaluation of a breast-cancer risk model
integrating classical risk factors and polygenic risk in 15
cohorts from six countries.},
journal = {International journal of epidemiology},
volume = {50},
number = {6},
issn = {1464-3685},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2021-00697},
pages = {1897–1911},
year = {2021},
note = {Volume 50, Issue 6, December 2021, Pages 1897–1911},
abstract = {Rigorous evaluation of the calibration and discrimination
of breast-cancer risk-prediction models in prospective
cohorts is critical for applications under clinical
guidelines. We comprehensively evaluated an integrated model
incorporating classical risk factors and a 313-variant
polygenic risk score (PRS) to predict breast-cancer
risk.Fifteen prospective cohorts from six countries with 239
340 women (7646 incident breast-cancer cases) of European
ancestry aged 19-75 years were included. Calibration of
5-year risk was assessed by comparing expected and observed
proportions of cases overall and within risk categories.
Risk stratification for women of European ancestry aged
50-70 years in those countries was evaluated by the
proportion of women and future cases crossing clinically
relevant risk thresholds.Among women <50 years old, the
median (range) expected-to-observed ratio for the integrated
model across 15 cohorts was 0.9 (0.7-1.0) overall and 0.9
(0.7-1.4) at the highest-risk decile; among women ≥50
years old, these were 1.0 (0.7-1.3) and 1.2 (0.7-1.6),
respectively. The proportion of women identified above a
$3\%$ 5-year risk threshold (used for recommending
risk-reducing medications in the USA) ranged from $7.0\%$ in
Germany (∼841 000 of 12 million) to $17.7\%$ in the USA
(∼5.3 of 30 million). At this threshold, $14.7\%$ of US
women were reclassified by adding the PRS to classical risk
factors, with identification of $12.2\%$ of additional
future cases.Integrating a 313-variant PRS with classical
risk factors can improve the identification of
European-ancestry women at elevated risk who could benefit
from targeted risk-reducing strategies under current
clinical guidelines.},
keywords = {Breast cancer (Other) / iCARE (Other) / model validation
(Other) / polygenic risk score (Other) / risk prediction
(Other) / risk stratification (Other)},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33755131},
doi = {10.1093/ije/dyab036},
url = {https://inrepo02.dkfz.de/record/168129},
}