Journal Article

DKFZ-2026-01857

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Clarifying risk-factor associations with quantitative breast tumor features: a pooled analysis of 24 studies.

Adams, D. ; Hurson, A. N. ; Ahearn, T. U. ; Andrulis, I. L. ; Antoniou, A. C. ; Auvinen, P. ; Bane, A. ; Behrens, S.DKFZ* ; Berrington de Gonzalez, A. ; Białkowska, K. ; Bodelon, C. ; Bolla, M. K. ; Borrero, M. ; Brenner, H.DKFZ* ; Brock, I. W. ; Broeks, A. ; Camp, N. J. ; Cessna, M. H. ; Chanock, S. J. ; Chenevix-Trench, G. ; Copson, E. ; Couch, F. J. ; Cox, A. ; Cross, S. S. ; Devilee, P. ; Dunning, A. M. ; Easton, D. F. ; Eccles, D. M. ; Figueroa, J. D. ; Glendon, G. ; González-Neira, A. ; Hamann, U.DKFZ* ; Hartikainen, J. M. ; Hartman, M. ; Heemskerk-Gerritsen, B. A. M. ; Ho, P. J. ; Hodge, J. M. ; Holleczek, B. ; Hollestelle, A. ; Hooning, M. J. ; Investigators, k. (Collaboration Author) ; Investigators, S. (Collaboration Author) ; Jakubowska, A. ; Jones, M. E. ; Jones, L. ; Jones, B. ; Jung, A. Y.DKFZ* ; Kaaks, R.DKFZ* ; Keeman, R. ; Lawrence, S. ; Li, J. ; Lissowska, J. ; Lubiński, J. ; Mannermaa, A. ; Manoochehri, M.DKFZ* ; Martens, J. W. M. ; Mesker, W. E. ; Muhammad, N. ; Mulligan, A. M. ; Obi, N. ; Olson, J. E. ; Osorio, A. ; Ottewell, P. D. ; Patel, A. V. ; Pita, G. ; Prajzendanc, K. ; Rashid, M. U. ; Ruddy, K. J. ; Safizadeh, F.DKFZ* ; Schöttker, B.DKFZ* ; Seibold, P.DKFZ* ; Tapper, W. J. ; Tengström, M. ; Teras, L. R. ; Thorne, H. ; Timmermans, M. A. M. ; Tollenaar, R. A. E. M. ; Vachon, C. M. ; Wang, Q. ; Wesseling, J. ; Yadav, S. ; Yang, X. R. ; Zamora, M. P. ; Chang-Claude, J.DKFZ* ; Schmidt, M. K. ; Pharoah, P. D. P. ; Abubakar, M. ; García-Closas, M. ; AmorTan, D. K. (Contributor) ; AndrewsTan, L. K. M. (Contributor) ; AntillLim, Y. H. (Contributor) ; BalleineTan, R. Y. (Contributor) ; BeesleyTan, J.-M. (Contributor) ; BennettIau, I. T. C. (Contributor) ; Bogwitz, M. (Contributor) ; Bodek, S. (Contributor) ; Botes, L. (Contributor) ; Brennan, M. (Contributor) ; Brown, M. (Contributor) ; Buckley, M. (Contributor) ; Caldon, L. (Contributor) ; Campbell, I. (Contributor) ; Chakrabarti, A. (Contributor) ; Chauhan, D. (Contributor) ; Chauhan, M. (Contributor) ; Chenevix-Trench, G. (Contributor) ; Christian, A. (Contributor) ; Cohen, P. (Contributor) ; Colley, A. (Contributor) ; Crook, A. (Contributor) ; Cui, J. (Contributor) ; Courtney, E. (Contributor) ; Cummings, M. (Contributor) ; Dawson, S.-J. (Contributor) ; deFazio, A. (Contributor) ; Delatycki, M. (Contributor) ; Dickson, R. (Contributor) ; Dixon, J. (Contributor) ; Duijf, P. (Contributor) ; Edwards, S. (Contributor) ; Farshid, G. (Contributor) ; Fellows, A. (Contributor) ; Fenton, G. (Contributor) ; Field, M. (Contributor) ; Flanagan, J. (Contributor) ; Fong, P. (Contributor) ; Forrest, L. (Contributor) ; Fox, S. (Contributor) ; French, J. (Contributor) ; Friedlander, M. (Contributor) ; Gattas, M. (Contributor) ; George, P. (Contributor) ; Greening, S. (Contributor) ; Harris, M. (Contributor) ; Harraka, P. (Contributor) ; Hayward, N. (Contributor) ; Hoskins, C. (Contributor) ; Hunt, C. (Contributor) ; James, P. (Contributor) ; Jenkins, M. (Contributor) ; Kidd, A. (Contributor) ; Koehler, J. (Contributor) ; Kollias, J. (Contributor) ; Lakhani, S. (Contributor) ; Lawrence, M. (Contributor) ; Lee, J. (Contributor) ; Li, S. (Contributor) ; Lindeman, G. (Contributor) ; Lippey, J. (Contributor) ; Lipton, L. (Contributor) ; Loi, S. (Contributor) ; Mann, G. (Contributor) ; Marsh, D. (Contributor) ; McLachlan, S. A. (Contributor) ; Reed, A. M. (Contributor) ; Milne, R. (Contributor) ; Nightingale, S. (Contributor) ; O'Connell, S. (Contributor) ; O'Sullivan, S. (Contributor) ; Reilly, R. O. (Contributor) ; Ortega, D. G. (Contributor) ; Pachter, N. (Contributor) ; Pang, J.-M. (Contributor) ; Pathak, G. (Contributor) ; Patterson, B. (Contributor) ; Pearn, A. (Contributor) ; Phillips, K. (Contributor) ; Pieper, E. (Contributor) ; Ramus, S. (Contributor) ; Rickard, E. (Contributor) ; Ragunathan, A. (Contributor) ; Robinson, B. (Contributor) ; Skandarajah, A. (Contributor) ; Salisbury, E. (Contributor) ; Saunders, C. (Contributor) ; Saunus, J. (Contributor) ; Savas, P. (Contributor) ; Scott, R. (Contributor) ; Scott, C. (Contributor) ; Sexton, A. (Contributor) ; Shaw, J. (Contributor) ; Shelling, A. (Contributor) ; Srinivasa, S. (Contributor) ; Simpson, P. (Contributor) ; Southey, M. (Contributor) ; Spurdle, A. (Contributor) ; Taylor, J. (Contributor) ; Taylor, R. (Contributor) ; Thorne, H. (Contributor) ; Trainer, A. (Contributor) ; Tucker, K. (Contributor) ; Visvader, J. (Contributor) ; Walker, L. (Contributor) ; Williams, R. (Contributor) ; Winship, I. (Contributor) ; Young, M. A. (Contributor) ; Zaheed, M. (Contributor)

2026
Oxford Univ. Press Oxford

Abstract: Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features.Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) <0.2 was used to identify associations with strong statistical evidence.Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend<0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend<0.001 and <0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend<0.001 and <0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units.This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.

Note: ISSN 1460-2105 / epub

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Contributing Institute(s):

1. Epidemiologie von Krebs (C020)
2. Koordinierungsstelle der Cancer Prevention GS (M320)
3. Molekulargenetik des Mammakarzinoms (B072)
4. Klinische Epidemiologie der Krebsfrüherkennung (C070)
5. Personalisierte Früherkennung des Prostatakarzinoms (C130)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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