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

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Chang-Claude, Jenny 
Ali, H Raza 
Chatterjee, Nilanjan 
Coulson, Penny 

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.

KI67, breast cancer, epidemiology, grade, hormone therapy, nulliparity, obesity, proliferation, Adult, Aged, Biomarkers, Tumor, Body Mass Index, Breast Neoplasms, Case-Control Studies, Cell Proliferation, Contraceptives, Oral, Hormonal, Female, Humans, Ki-67 Antigen, Middle Aged, Neoplasm Grading, Obesity, Parity, Receptors, Estrogen, Receptors, Progesterone, Risk Factors
Journal Title
Int J Cancer
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Volume Title
Cancer Research Uk (None)
European Commission Horizon 2020 (H2020) Societal Challenges (633784)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research UK (A25117)
Cancer Research UK (C14303/A17197)
Cancer Research UK (25815)