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


Change log
Authors
Chang-Claude, Jenny 
Ali, H Raza 
Chatterjee, Nilanjan 
Coulson, Penny 
Abstract

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.

Description
Keywords
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
Conference Name
Journal ISSN
0020-7136
1097-0215
Volume Title
143
Publisher
Wiley
Sponsorship
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)