TY - JOUR
T1 - Etiology of hormone receptor positive breast cancer differs by levels of histologic grade and proliferation
AU - KConFab investigators
AU - Abubakar, Mustapha
AU - Chang-Claude, Jenny
AU - Ali, H. Raza
AU - Chatterjee, Nilanjan
AU - Coulson, Penny
AU - Daley, Frances
AU - Blows, Fiona
AU - Benitez, Javier
AU - Milne, Roger L.
AU - Brenner, Hermann
AU - Stegmaier, Christa
AU - Mannermaa, Arto
AU - Rudolph, Anja
AU - Sinn, Peter
AU - Couch, Fergus J.
AU - Devilee, Peter
AU - Tollenaar, Rob A.E.M.
AU - Seynaeve, Caroline
AU - Figueroa, Jonine
AU - Lissowska, Jolanta
AU - Hewitt, Stephen
AU - Hooning, Maartje J.
AU - Hollestelle, Antoinette
AU - Foekens, Renée
AU - Koppert, Linetta B.
AU - Bolla, Manjeet K.
AU - Wang, Qin
AU - Jones, Michael E.
AU - Schoemaker, Minouk J.
AU - Keeman, Renske
AU - Easton, Douglas F.
AU - Swerdlow, Anthony J.
AU - Sherman, Mark E.
AU - Schmidt, Marjanka K.
AU - Pharoah, Paul D.
AU - Garcia-Closas, Montserrat
N1 - Publisher Copyright:
© 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
PY - 2018/8/15
Y1 - 2018/8/15
N2 - 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.
AB - 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.
KW - KI67
KW - breast cancer
KW - epidemiology
KW - grade
KW - hormone therapy
KW - nulliparity
KW - obesity
KW - proliferation
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U2 - 10.1002/ijc.31352
DO - 10.1002/ijc.31352
M3 - Article
C2 - 29492969
AN - SCOPUS:85044738114
SN - 0020-7136
VL - 143
SP - 746
EP - 757
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 4
ER -