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@ARTICLE{Brantley:300748,
author = {K. D. Brantley and M. E. Jones and R. M. Tamimi and B. A.
Rosner and P. Kraft and H. B. Nichols and K. M. O'Brien and
H.-O. Adami and A. Aizpurua and A. B. de Gonzalez and W. J.
Blot and T. Braaten and Y. Chen and J. C. DeHart and L.
Dossus and S. Elias and R. Turzanski-Fortner$^*$ and M.
Garcia-Closas and I. T. Gram and N. Håkansson and S. E.
Hankinson and C. M. Kitahara and W.-P. Koh and M. S. Linet
and R. J. MacInnis and G. Masala and L. Mellemkjær and R.
L. Milne and D. C. Muller and H. L. Park and K. J. Ruddy and
S. Sandin and X.-O. Shu and S. Tin Tin and T. Truong and C.
M. Vachon and L. J. Vatten and K. Visvanathan and E.
Weiderpass and W. Willett and A. Wolk and J.-M. Yuan and W.
Zheng and D. P. Sandler and M. J. Schoemaker and A. J.
Swerdlow and A. H. Eliassen},
title = {{D}evelopment and validation of a risk prediction model for
premenopausal breast cancer in 19 cohorts.},
journal = {Breast cancer research},
volume = {27},
number = {1},
issn = {1465-5411},
address = {London},
publisher = {BioMed Central},
reportid = {DKFZ-2025-00908},
pages = {67},
year = {2025},
abstract = {Incidence of premenopausal breast cancer (BC) has risen in
recent years, though most existing BC prediction models are
not generalizable to young women due to underrepresentation
of this age group in model development.Using
questionnaire-based data from 19 prospective studies
harmonized within the Premenopausal Breast Cancer
Collaborative Group (PBCCG), representing 783,830 women, we
developed a premenopausal BC risk prediction model. The data
were split into training (2/3) and validation (1/3) datasets
with equal distribution of cohorts in each. In the training
dataset variables were chosen from known and hypothesized
risk factors: age, age at menarche, age at first birth,
parity, breastfeeding, height, BMI, young adulthood BMI,
recent weight change, alcohol consumption, first-degree
family history of BC, and personal history of benign breast
disease (BBD). Hazard ratios (HR) and $95\%$ confidence
intervals (CI) were estimated by Cox proportional hazards
regression using age as time scale, stratified by cohort.
Given that complete information on all risk factors was not
available in all cohorts, coefficients were estimated
separately in groups of cohorts with the same available
covariate information, adjusted to account for the
correlation between missing and non-missing variables and
meta-analyzed. Absolute risk of BC (in situ or invasive)
within 5 years, was determined using country-, age-, and
birth cohort-specific incidence rates. Discrimination (area
under the curve, AUC) and calibration (Expected/Observed,
E/O) were evaluated in the validation dataset. We compared
our model with a literature-based model for women < 50 years
(iCARE-Lit).Selected model risk factors were age at
menarche, parity, height, current and young adulthood BMI,
family history of BC, and personal BBD history. Predicted
absolute 5-year risk ranged from $0\%$ to $5.7\%.$ The model
overestimated risk on average [E/O risk = 1.18 (1.14-1.23)],
with underestimation of risk in lower absolute risk deciles
and overestimation in upper absolute risk deciles [E/O 1st
decile = 0.59 (0.58-0.60); E/O 10th decile = 1.48
(1.48-1.49)]. The AUC was $59.1\%$ $(58.1-60.1\%).$
Performance was similar to the iCARE-Lit model.In this
prediction model for premenopausal BC, the relative
contribution of risk factors to absolute risk was similar to
existing models for overall BC. The discriminatory ability
was nearly identical (< $1\%$ difference in AUC) to the
existing iCARE-Lit model developed in women under 50 years.
The inability to improve discrimination highlights the need
to investigate additional predictors to better understand
premenopausal BC risk.},
keywords = {Premenopausal breast cancer (Other) / Risk prediction model
(Other) / Young-onset breast cancer (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:40312753},
doi = {10.1186/s13058-025-02031-8},
url = {https://inrepo02.dkfz.de/record/300748},
}