Circulating estrogen metabolites and risk of breast cancer in postmenopausal women.
BACKGROUND
It has been hypothesized that predominance of the 2-hydroxylation estrogen metabolism pathway over the 16α-hydroxylation pathway may be inversely associated with breast cancer risk.


METHODS
We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1), and the 2-OHE1:16α-OHE1 ratio in a case-control study of postmenopausal women nested within two prospective cohorts: the New York University Women's Health Study (NYUWHS) and the Northern Sweden Mammary Screening Cohort (NSMSC), with adjustment for circulating levels of estrone, and additional analyses by tumor estrogen receptor (ER) status. Levels of 2-OHE1 and 16α-OHE1 were measured using ESTRAMET 2/16 assay in stored serum or plasma samples from 499 incident breast cancer cases and 499 controls, who were matched on cohort, age, and date of blood donation.


RESULTS
Overall, no significant associations were observed between breast cancer risk and circulating levels of 2-OHE1, 16α-OHE1, or their ratio in either cohort and in combined analyses. For 2-OHE1, there was evidence of heterogeneity by ER status in models adjusting for estrone (P ≤ 0.03). We observed a protective association of 2-OHE1 with ER+ breast cancer [multivariate-adjusted OR for a doubling of 2-OHE1, 0.67 (95% confidence interval [CI], 0.48-0.94; P = 0.02)].


CONCLUSIONS
In this study, higher levels of 2-OHE1 were associated with reduced risk of ER+ breast cancer in postmenopausal women after adjustment for circulating estrone.


CONCLUSIONS
These results suggest that taking into account the levels of parent estrogens and ER status is important in studies of estrogen metabolites and breast cancer.
Authors' Affiliations: Departments of Obstetrics and Gynecology, Population Health, and Environmental Medicine, New York University School of Medicine; New York University Cancer Institute, New York, New York; Departments of.
Alan A
AA
Arslan
Population Health, and Environmental Medicine, New York University School of Medicine;
Karen L
KL
Koenig
Radiation Sciences/Oncology.
Per
P
Lenner
Population Health, and.
Yelena
Y
Afanasyeva
Radiation Effects Research Foundation, Hiroshima, Japan.
Roy E
RE
Shore
Population Health, and Environmental Medicine, New York University School of Medicine; New York University Cancer Institute, New York, New York; Departments of.
Yu
Y
Chen
Medical Biosciences/Pathology, and.
Eva
E
Lundin
Authors' Affiliations: Departments of Obstetrics and Gynecology, New York University Cancer Institute, New York, New York; Departments of.
Paolo
P
Toniolo
Public Health and Clinical Medicine/Nutritional Research, Umeå University, Umeå, Sweden; and.
Göran
G
Hallmans
Population Health, and Environmental Medicine, New York University School of Medicine; New York University Cancer Institute, New York, New York; Departments of Anne.Jacquotte@nyumc.org.
Anne
A
Zeleniuch-Jacquotte
D001943:Breast Neoplasms / Q000097:blood*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D004967:Estrogens / Q000378:metabolism*; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause; D012306:Risk
D004967:Estrogens; D006894:Hydroxyestrones; D004970:Estrone; C024980:2-hydroxyestrone