Etiology of hormone receptor positive breast cancer differs by levels of histologic grade and proliferation
Title | Etiology of hormone receptor positive breast cancer differs by levels of histologic grade and proliferation |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Abubakar, M, Chang-Claude, J, Ali, HR, Chatterjee, N, Coulson, P, Daley, F, Blows, F, Benitez, J, Milne, RL, Brenner, H, Stegmaier, C, Mannermaa, A, Rudolph, A, Sinn, P, Couch, FJ, Devilee, P, Tollenaar, R, Seynaeve, C, Figueroa, J, Lissowska, J, Hewitt, S, Hooning, MJ, Hollestelle, A, Foekens, R, Koppert, LB, Investigators, K, Bolla, MK, Wang, Q, Jones, ME, Schoemaker, MJ, Keeman, R, Easton, DF, Swerdlow, AJ, Sherman, ME, Schmidt, MK, Pharoah, PD, Garcia-Closas, M |
Journal | Int J Cancer |
Volume | 143 |
Pagination | 746-757 |
Date Published | Aug 15 |
ISBN Number | 0020-7136 |
Accession Number | 29492969 |
Keywords | breast cancer, Epidemiology, grade, hormone therapy, Ki67, nulliparity, Obesity, 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. |
PMCID | PMC6041155 |