Etiology of hormone receptor positive breast cancer differs by levels of histologic grade and proliferation.
- 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.
- Authors:
- M Abubakar, J Chang-Claude, HR Ali, N Chatterjee, P Coulson, F Daley, F Blows, J Benitez, RL Milne, H Brenner, C Stegmaier, A Mannermaa, A Rudolph, P Sinn, FJ Couch, P Devilee, RAEM Tollenaar, C Seynaeve, J Figueroa, J Lissowska, S Hewitt, MJ Hooning, A Hollestelle, R Foekens, LB Koppert, kConFab Investigators, MK Bolla, Q Wang, ME Jones, MJ Schoemaker, R Keeman, DF Easton, AJ Swerdlow, ME Sherman, MK Schmidt, PD Pharoah, M Garcia-Closas
- Journal:
- Int J Cancer
- Citation info:
- 143(4):746-757
- Publication date:
- 15th Aug 2018
- Full text
- DOI