BACKGROUND: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1), and their ratio (2:16α-OHE1) in relation to breast cancer risk. METHODS: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status. RESULTS: Higher premenopausal 2:16α-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16α-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003). CONCLUSIONS: Premenopausal urinary 2:16α-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16α-OHE1 overall, although obesity may modify associations with 2-OHE1.
BACKGROUND: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1), and their ratio (2:16α-OHE1) in relation to breast cancer risk. METHODS: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status. RESULTS: Higher premenopausal 2:16α-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16α-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003). CONCLUSIONS: Premenopausal urinary 2:16α-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16α-OHE1 overall, although obesity may modify associations with 2-OHE1.
Authors: Cher M Dallal; Jeffrey A Tice; Diana S M Buist; Douglas C Bauer; James V Lacey; Jane A Cauley; Trisha F Hue; Andrea Lacroix; Roni T Falk; Ruth M Pfeiffer; Barbara J Fuhrman; Timothy D Veenstra; Xia Xu; Louise A Brinton Journal: Carcinogenesis Date: 2013-11-08 Impact factor: 4.944
Authors: Terryl J Hartman; Julia S Sisti; Susan E Hankinson; Xia Xu; A Heather Eliassen; Regina Ziegler Journal: Horm Cancer Date: 2016-01-04 Impact factor: 3.869
Authors: Essam R Othman; Ahmad Abo Markeb; Maha Y Khashbah; Ibrahim I Abdelaal; Tarek T ElMelegy; Ahmed N Fetih; Lisette E Van der Houwen; Cornelis B Lambalk; Velja Mijatovic Journal: Reprod Sci Date: 2020-11-20 Impact factor: 3.060
Authors: Cher M Dallal; James V Lacey; Ruth M Pfeiffer; Douglas C Bauer; Roni T Falk; Diana S M Buist; Jane A Cauley; Trisha F Hue; Andrea Z LaCroix; Jeffrey A Tice; Timothy D Veenstra; Xia Xu; Louise A Brinton Journal: Horm Cancer Date: 2016-01-04 Impact factor: 3.869
Authors: Lauren C Houghton; Renata E Howland; Ying Wei; Xinran Ma; Rebecca D Kehm; Wendy K Chung; Jeanine M Genkinger; Regina M Santella; Michaela F Hartmann; Stefan A Wudy; Mary Beth Terry Journal: Cancer Epidemiol Biomarkers Prev Date: 2020-09-30 Impact factor: 4.090