TY - JOUR
T1 - Etiology of hormone receptor positive breast cancer differs by levels of histologic grade and proliferation
AU - KConFab investigators
AU - Abubakar, Mustapha
AU - Chang-Claude, Jenny
AU - Ali, H. Raza
AU - Chatterjee, Nilanjan
AU - Coulson, Penny
AU - Daley, Frances
AU - Blows, Fiona
AU - Benitez, Javier
AU - Milne, Roger L.
AU - Brenner, Hermann
AU - Stegmaier, Christa
AU - Mannermaa, Arto
AU - Rudolph, Anja
AU - Sinn, Peter
AU - Couch, Fergus J.
AU - Devilee, Peter
AU - Tollenaar, Rob A.E.M.
AU - Seynaeve, Caroline
AU - Figueroa, Jonine
AU - Lissowska, Jolanta
AU - Hewitt, Stephen
AU - Hooning, Maartje J.
AU - Hollestelle, Antoinette
AU - Foekens, Renée
AU - Koppert, Linetta B.
AU - Bolla, Manjeet K.
AU - Wang, Qin
AU - Jones, Michael E.
AU - Schoemaker, Minouk J.
AU - Keeman, Renske
AU - Easton, Douglas F.
AU - Swerdlow, Anthony J.
AU - Sherman, Mark E.
AU - Schmidt, Marjanka K.
AU - Pharoah, Paul D.
AU - Garcia-Closas, Montserrat
N1 - Funding Information:
We acknowledge funds from Breakthrough Breast Cancer (Breast Cancer Now), UK, in support of MGC at the time part of this work was carried out and funds from the Cancer Research, UK (CRUK), in support of MA at the
Funding Information:
Key words: breast cancer, epidemiology, obesity, nulliparity, hormone therapy, grade, KI67, proliferation Abbreviations: BCAC: Breast Cancer Association Consortium; BMI: body mass index; ER: estrogen receptor; HR1: hormone receptor positive; HT: hormone therapy; ICR: Institute of Cancer Research, London; NGS: Nottingham grading system; OR: odds ratio; PR: progesterone receptor; TMA: tissue microarray Additional Supporting Information may be found in the online version of this article. Conflict of interest: The authors declare that they have no conflicts of interest. Grant sponsor: Baden Wu€rttemberg Ministry of Science, Research and Arts; Grant sponsor: The German Cancer Aid (Deutsche Krebshilfe); Grant sponsor: Government Funding (EVO) of Kuopio University Hospital; Grant sponsor: Cancer Fund of North Savo; Grant sponsor: Finnish Cancer Organizations; Grant sponsor: The Academy of Finland and by the strategic funding of the University of Eastern Finland; Grant sponsor: Deutsche Krebshilfe e.V.; Grant numbers: 70-2892-BR I, 106332, 108253, 108419; Grant sponsor: The Hamburg Cancer Society; Grant sponsor: The German Cancer Research Center (DKFZ); Grant sponsor: The Federal Ministry of Education and Research (BMBF) Germany; Grant number: 01KH0402; Grant sponsor: National Institutes of Health Specialized Program of Research Excellence (SPORE) in Breast Cancer; Grant number: CA116201; Grant sponsor: The Breast Cancer Research Foundation; Grant sponsor: The Mayo Clinic Breast Cancer Registry and a generous gift from the David F. and Margaret T. Grohne Family Foundation; Grant sponsor: The Ting Tsung and Wei Fong Chao Foundation; Grant sponsor: The Dutch Cancer Society; Grant number: UL1997-1505; Grant sponsor: The Biobanking and Biomolecular Resources Research Infrastructure; Grant number: BBMRI-NL CP16; Grant sponsor: Dutch Cancer Society; Grant numbers: DDHK 2004-3124, DDHK 2009-4318; Grant sponsor: Cancer Research UK; Grant numbers: C490/ A10124, C490/A16561; Grant sponsor: UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge; Grant sponsor: European Community’s Seventh Framework Programme; Grant number: HEALTH-F2-2009223175; Grant sponsor: Breakthrough Breast Cancer (Breast Cancer Now) ; Grant sponsor: The Institute of Cancer Research, London; Grant sponsor: Intramural Research Funds of the National Cancer Institute, Division of Cancer Epidemiology and Genetics, National Institutes of Health, USA. DOI: 10.1002/ijc.31352 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. History: Received 3 Nov 2017; Accepted 26 Jan 2018; Online 1 Mar 2018 Correspondence to: Mustapha Abubakar, Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850, USA, Tel.: 1-240-276-5091, E-mail: mustapha.abubakar2@nih.gov
Funding Information:
We acknowledge funds from Breakthrough Breast Cancer (Breast Cancer Now), UK, in support of MGC at the time part of this work was carried out and funds from the Cancer Research, UK (CRUK), in support of MA at the Division of Genetics and Epidemiology, Institute of Cancer Research, London at the time part of this work was carried out. We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia and the Cancer Foundation of Western Australia.
Publisher Copyright:
© 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
PY - 2018/8/15
Y1 - 2018/8/15
N2 - Limited epidemiological evidence suggests that the etiology of hormone receptor positive (HR+) breast cancer may differ by levels of histologic grade and proliferation. We pooled risk factor and pathology data on 5,905 HR+ breast cancer cases and 26,281 controls from 11 epidemiological studies. Proliferation was determined by centralized automated measures of KI67 in tissue microarrays. Odds ratios (OR), 95% confidence intervals (CI) and p-values for case–case and case–control comparisons for risk factors in relation to levels of grade and quartiles (Q1–Q4) of KI67 were estimated using polytomous logistic regression models. Case–case comparisons showed associations between nulliparity and high KI67 [OR (95% CI) for Q4 vs. Q1 = 1.54 (1.22, 1.95)]; obesity and high grade [grade 3 vs. 1 = 1.68 (1.31, 2.16)] and current use of combined hormone therapy (HT) and low grade [grade 3 vs. 1 = 0.27 (0.16, 0.44)] tumors. In case–control comparisons, nulliparity was associated with elevated risk of tumors with high but not low levels of proliferation [1.43 (1.14, 1.81) for KI67 Q4 vs. 0.83 (0.60, 1.14) for KI67 Q1]; obesity among women ≥50 years with high but not low grade tumors [1.55 (1.17, 2.06) for grade 3 vs. 0.88 (0.66, 1.16) for grade 1] and HT with low but not high grade tumors [3.07 (2.22, 4.23) for grade 1 vs. 0.85 (0.55, 1.30) for grade 3]. Menarcheal age and family history were similarly associated with HR+ tumors of different grade or KI67 levels. These findings provide insights into the etiologic heterogeneity of HR+ tumors.
AB - Limited epidemiological evidence suggests that the etiology of hormone receptor positive (HR+) breast cancer may differ by levels of histologic grade and proliferation. We pooled risk factor and pathology data on 5,905 HR+ breast cancer cases and 26,281 controls from 11 epidemiological studies. Proliferation was determined by centralized automated measures of KI67 in tissue microarrays. Odds ratios (OR), 95% confidence intervals (CI) and p-values for case–case and case–control comparisons for risk factors in relation to levels of grade and quartiles (Q1–Q4) of KI67 were estimated using polytomous logistic regression models. Case–case comparisons showed associations between nulliparity and high KI67 [OR (95% CI) for Q4 vs. Q1 = 1.54 (1.22, 1.95)]; obesity and high grade [grade 3 vs. 1 = 1.68 (1.31, 2.16)] and current use of combined hormone therapy (HT) and low grade [grade 3 vs. 1 = 0.27 (0.16, 0.44)] tumors. In case–control comparisons, nulliparity was associated with elevated risk of tumors with high but not low levels of proliferation [1.43 (1.14, 1.81) for KI67 Q4 vs. 0.83 (0.60, 1.14) for KI67 Q1]; obesity among women ≥50 years with high but not low grade tumors [1.55 (1.17, 2.06) for grade 3 vs. 0.88 (0.66, 1.16) for grade 1] and HT with low but not high grade tumors [3.07 (2.22, 4.23) for grade 1 vs. 0.85 (0.55, 1.30) for grade 3]. Menarcheal age and family history were similarly associated with HR+ tumors of different grade or KI67 levels. These findings provide insights into the etiologic heterogeneity of HR+ tumors.
KW - KI67
KW - breast cancer
KW - epidemiology
KW - grade
KW - hormone therapy
KW - nulliparity
KW - obesity
KW - proliferation
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U2 - 10.1002/ijc.31352
DO - 10.1002/ijc.31352
M3 - Article
C2 - 29492969
AN - SCOPUS:85044738114
VL - 143
SP - 746
EP - 757
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 4
ER -