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Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium Studies

Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium Studies
Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium Studies
BACKGROUND: Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.

METHODS: We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided.

RESULTS: In case-case analyses, of the epidemiological risk factors examined, early age at menarche (?12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ? 30 kg/m(2)) in younger women (?50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors.

CONCLUSIONS: This study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.
0027-8874
250-263
Yang, X.R.
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Chang-Claude, J.
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Goode, E.L.
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Couch, F.J.
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Nevanlinna, H.
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Milne, R. L.
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Gaudet, M.
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Cox, A.
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Driver, K.
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Flesch-Janys, D.
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Blomqvist, C.
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Figueroa, J.
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Liu, J.
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Weerasooriya, N.
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Yang, X.R., Chang-Claude, J. and Goode, E.L. et al. (2011) Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium Studies. JNCI Journal of the National Cancer Institute, 103 (3), 250-263. (doi:10.1093/jnci/djq526). (PMID:21191117)

Record type: Article

Abstract

BACKGROUND: Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.

METHODS: We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided.

RESULTS: In case-case analyses, of the epidemiological risk factors examined, early age at menarche (?12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ? 30 kg/m(2)) in younger women (?50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors.

CONCLUSIONS: This study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.

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Accepted/In Press date: 23 November 2010
e-pub ahead of print date: 29 December 2010
Published date: 2011
Organisations: Cancer Sciences, Clinical Trials Unit

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Local EPrints ID: 383065
URI: http://eprints.soton.ac.uk/id/eprint/383065
DOI: doi:10.1093/jnci/djq526
ISSN: 0027-8874
PURE UUID: 2781aca7-74af-462e-8dad-66bcfe510e6c
ORCID for D. M. Eccles: ORCID iD orcid.org/0000-0002-9935-3169
ORCID for W.J. Tapper: ORCID iD orcid.org/0000-0002-5896-1889

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Date deposited: 20 Oct 2015 11:12
Last modified: 15 Mar 2024 03:02

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Contributors

Author: X.R. Yang
Author: J. Chang-Claude
Author: E.L. Goode
Author: F.J. Couch
Author: H. Nevanlinna
Author: R. L. Milne
Author: M. Gaudet
Author: M. K. Schmidt
Author: A. Broeks
Author: A. Cox
Author: P. A. Fasching
Author: R. Hein
Author: A. B. Spurdle
Author: F. Blows
Author: K. Driver
Author: D. Flesch-Janys
Author: J. Heinz
Author: P. Sinn
Author: A. Vrieling
Author: T. Heikkinen
Author: K. Aittomaki
Author: P. Heikkila
Author: C. Blomqvist
Author: J. Lissowska
Author: B. Peplonska
Author: S. Chanock
Author: J. Figueroa
Author: L. Brinton
Author: P. Hall
Author: K. Czene
Author: K. Humphreys
Author: H. Darabi
Author: J. Liu
Author: L. J. Van 't Veer
Author: F. E. van Leeuwen
Author: I. L. Andrulis
Author: G. Glendon
Author: J. A. Knight
Author: A. M. Mulligan
Author: F. P. O'Malley
Author: N. Weerasooriya
Author: E. M. John
Author: M. W. Beckmann
Author: A. Hartmann
Author: S. B. Weihbrecht
Author: D. L. Wachter
Author: S. M. Jud
Author: C. R. Loehberg
Author: L. Baglietto
Author: D. R. English
Author: G. G. Giles
Author: C. A. McLean
Author: G. Severi
Author: D. Lambrechts
Author: T. Vandorpe
Author: C. Weltens
Author: R. Paridaens
Author: A. Smeets
Author: P. Neven
Author: H. Wildiers
Author: X. Wang
Author: J. E. Olson
Author: V. Cafourek
Author: Z. Fredericksen
Author: M. Kosel
Author: C. Vachon
Author: H. E. Cramp
Author: D. Connley
Author: S. S. Cross
Author: S. P. Balasubramanian
Author: M. W. R. Reed
Author: T. Dork
Author: M. Bremer
Author: A. Meyer
Author: J. H. Karstens
Author: A. Ay
Author: T.-W. Park-Simon
Author: P. Hillemanns
Author: J. I. Arias Perez
Author: P. M. Rodriguez
Author: P. Zamora
Author: J. Benitez
Author: Y.-D. Ko
Author: H.-P. Fischer
Author: U. Hamann
Author: B. Pesch
Author: T. Bruning
Author: C. Justenhoven
Author: H. Brauch
Author: D. M. Eccles ORCID iD
Author: W.J. Tapper ORCID iD
Author: S.M. Gerty
Author: E. J. Sawyer
Author: I. P. Tomlinson
Author: A. Jones
Author: M. Kerin
Author: N. Miller
Author: N. McInerney
Author: H. Anton-Culver
Author: A. Ziogas
Author: C.-Y. Shen
Author: C.-N. Hsiung
Author: P.-E. Wu
Author: S.-L. Yang
Author: J.-C. Yu
Author: S.-T. Chen
Author: G.-C. Hsu
Author: C. A. Haiman
Author: B. E. Henderson
Author: L. Le Marchand
Author: L. N. Kolonel
Author: A. Lindblom
Author: S. Margolin
Author: A. Jakubowska
Author: J. Lubinski
Author: T. Huzarski
Author: T. Byrski
Author: B. Gorski
Author: J. Gronwald
Author: M. J. Hooning
Author: A. Hollestelle
Author: A. M. W. van den Ouweland
Author: A. Jager
Author: M. Kriege
Author: M. M. A. Tilanus-Linthorst
Author: M. Collee
Author: S. Wang-Gohrke
Author: K. Pylkas
Author: A. Jukkola-Vuorinen
Author: K. Mononen
Author: M. Grip
Author: P. Hirvikoski
Author: R. Winqvist
Author: A. Mannermaa
Author: V.-M. Kosma
Author: J. Kauppinen
Author: V. Kataja
Author: P. Auvinen
Author: Y. Soini
Author: R. Sironen
Author: S. E. Bojesen
Author: D. Dynnes Orsted
Author: D. Kaur-Knudsen
Author: H. Flyger
Author: B. G. Nordestgaard
Author: H. Holland
Author: G. Chenevix-Trench
Author: S. Manoukian
Author: M. Barile
Author: P. Radice
Author: S. E. Hankinson
Author: D. J. Hunter
Author: R. Tamimi
Author: S. Sangrajrang
Author: P. Brennan
Author: J. McKay
Author: F. Odefrey
Author: V. Gaborieau
Author: P. Devilee
Author: P. E. A. Huijts
Author: R. Tollenaar
Author: C. Seynaeve
Author: G. S. Dite
Author: C. Apicella
Author: J. L. Hopper
Author: F. Hammet
Author: H. Tsimiklis
Author: L. D. Smith
Author: M. C. Southey
Author: M. K. Humphreys
Author: D. Easton
Author: P. Pharoah
Author: M. E. Sherman
Author: M. Garcia-Closas

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