Etiology of hormone receptor positive breast cancer differs by levels of histologic grade and proliferation

Mustapha Abubakar, Jenny Chang-Claude, Hamid Raza Ali, Nilangan Chatterjee, Penny Coulson, Frances Daley, Fiona Blows, Javier J. Benitez, Roger L Milne, Hermann Brenner, Christa Stegmaier, Arto Mannermaa, Anja Rudolph, Peter Sinn, Fergus J Couch, Peter Devilee, Rob Aem Tollenaar, Caroline Seynaeve, Jonine Figueroa, Jolanta LissowskaStephen M. Hewitt, Maartje J Hooning, Antoinette Hollestelle, Renée Foekens, Linetta B Koppert, Kconfab Investigators, Manjeet K Bolla, Yi-Qin Wang, Michael E Jones, Minouk J Schoemaker, Renske Keeman, Douglas F. Easton, Anthony J. Swerdlow, Mark E Sherman, Marjanka K Schmidt, Paul D. P. Pharoah, Montserrat Garcia-Closas

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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. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalInternational Journal of Cancer
Early online date1 Mar 2018
Publication statusE-pub ahead of print - 1 Mar 2018


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