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@ARTICLE{LeCornet:302816,
author = {C. Le Cornet$^*$ and A. Y. Jung$^*$ and S. Behrens$^*$ and
P. Middha$^*$ and T. Truong and H. Jernström and M. K.
Bolla and Q. Wang and M. C. Southey and L. E. Beane Freeman
and S. Koutros and J. Stone and G. Rennert and K. Shulman
and K. J. Aronson and R. A. Murphy and P. Guénel and A. V.
Patel and C. Bodelon and L. R. Teras and S. Shahi and J. V.
Lacey and L. Dossus and R. Kaaks$^*$ and B. Holleczek and H.
Brenner$^*$ and H. Brauch$^*$ and R. Hoppe and K. Czene and
P. F. L. Hall and A. Mannermaa and A. H. Wu and N. Obi and
K. Michailidou and M. I. Panayiotidis and C. McLean and C.
A. Haiman and A. Augustinsson and W. Zheng and X.-O. Shu and
C. M. Perou and M. A. Troester and S. Van Alsten and A. H.
Eliassen and M. Abubakar and P. Kraft and T. U. Ahearn and
D. G. Evans and A. Wolk and R. L. Milne and D. F. Easton and
P. D. P. Pharoah and M. K. Schmidt and M. García-Closas and
C. M. Vachon and R. Turzanski-Fortner$^*$ and J.
Chang-Claude$^*$},
title = {{E}xogenous {H}ormones, {T}umor {I}ntrinsic {S}ubtypes, and
{B}reast {C}ancer.},
journal = {JAMA network open},
volume = {8},
number = {7},
issn = {2574-3805},
address = {Chicago, Ill.},
publisher = {American Medical Association},
reportid = {DKFZ-2025-01356},
pages = {e2519236},
year = {2025},
note = {#EA:C020#LA:C020#},
abstract = {Etiologic heterogeneity in breast carcinogenesis needs to
be well characterized for targeted prevention. Associations
between menopausal hormonal therapy (MHT) and oral
contraceptive (OC) use and breast cancer intrinsic-like
subtypes are not well understood.To examine whether
exogenous hormone use is differentially associated with
breast cancer subtypes and to evaluate heterogeneity by
intrinsic-like subtypes.This study pooled data from 31
nested and population-based case-control studies involved in
the Breast Cancer Association Consortium. The study
population included individuals with breast cancer and
control participants from 13 case-control studies nested in
prospective cohorts (recruited between 1982 and 2011) and 18
population-based case-control studies (recruited between
1990 and 2013). Data analysis was performed in June 2024.MHT
use (estrogen-progestin therapy [EPT] or estrogen-only
therapy [ET]) in postmenopausal women and OC use in
premenopausal women (never, past use, or current use).Breast
cancer intrinsic-like subtypes (luminal A-like, luminal
B-like, luminal B-ERBB2 [formerly HER2 or HER2/neu]-like,
ERBB2 enriched-like, or triple-negative) were determined by
immunohistochemistry of tumor sections. Polytomous logistic
regression was performed to estimate the association between
exogenous hormones and risk of breast cancer by
intrinsic-like subtypes. Analyses by subtypes were
stratified by body mass index (BMI [calculated as weight in
kilograms divided by height in meters squared]; healthy
weight, 18.5-<25; overweight, 25-<30; or obesity,
≥30).This study included 42 269 individuals with breast
cancer (11 901 $[28.2\%]$ premenopausal and 30 368
$[71.8\%]$ postmenopausal; 23 353 $[55.2\%]$ had a known
intrinsic-like subtype) and 71 072 control participants. The
mean (SD) age of all participants was 57.9 (10.9) years. In
postmenopausal women, associations between current MHT use
(EPT or ET) and breast cancer differed by subtype. Current
EPT users with healthy weight were more likely to be
diagnosed with luminal A-like (odds ratio [OR], 2.51 $[95\%$
CI, 2.26-2.80]) or luminal B-ERBB2-like (OR, 1.95 $[95\%$
CI, 1.61-2.37]) subtypes. These associations were attenuated
but remained for individuals with overweight (OR, 1.40
$[95\%$ CI, 1.02-1.92]) or obesity (OR, 1.68 $[95\%$ CI,
1.01-2.78]). EPT use increased the odds of being diagnosed
with luminal B-like tumors solely in women with healthy
weight (OR, 1.47 $[95\%$ CI, 1.17-1.86]). Current ET use was
positively associated with luminal A-like disease in women
with healthy weight only (OR, 1.16 $[95\%$ CI, 1.01-1.32]),
showing inverse associations with higher BMI (obesity: OR,
0.65 $[95\%$ CI, 0.50-0.85]). In premenopausal women, recent
OC use was associated with luminal B-ERBB2-like (OR, 1.50
$[95\%$ CI, 1.09-2.08]), ERBB2 enriched-like (OR, 2.33
$[95\%$ CI, 1.55-3.51]), and triple-negative (OR, 1.75
$[95\%$ CI, 1.33-2.29]; P < .04 for heterogeneity) tumors.In
this study, clear differences were observed in associations
between current EPT use and luminal-like breast cancer
subtypes and other subtypes. EPT users with healthy weight
were more likely to be diagnosed with luminal-like breast
cancer compared with nonusers. Subtype heterogeneity was
less apparent in associations of OC and ET use. Future
studies on contemporary formulations, patterns of use, and
routes of administration of exogenous hormone usage are
warranted.},
keywords = {Humans / Female / Breast Neoplasms: epidemiology / Breast
Neoplasms: classification / Breast Neoplasms: chemically
induced / Breast Neoplasms: pathology / Middle Aged /
Case-Control Studies / Postmenopause / Adult / Prospective
Studies / Aged / Contraceptives, Oral: adverse effects /
Premenopause / Estrogen Replacement Therapy: adverse effects
/ Estrogen Replacement Therapy: statistics $\&$ numerical
data / Contraceptives, Oral (NLM Chemicals)},
cin = {C020 / C070 / HD01 / TU01},
ddc = {610},
cid = {I:(DE-He78)C020-20160331 / I:(DE-He78)C070-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)TU01-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40622713},
pmc = {pmc:PMC12235495},
doi = {10.1001/jamanetworkopen.2025.19236},
url = {https://inrepo02.dkfz.de/record/302816},
}