Estrogen metabolism and mammographic density in postmenopausal women: a cross-sectional study.
BACKGROUND
Prospective studies have consistently found that postmenopausal breast cancer risk increases with circulating estrogens; however, findings from studies of estrogens and mammographic density (MD), an intermediate marker of breast cancer risk, have been inconsistent. We investigated the cross-sectional associations of urinary estrogens, and their 2-, 4-, and 16-hydroxylated metabolites with MD.


METHODS
Postmenopausal women without breast cancer (n = 194), ages 48 to 82 years, and reporting no current menopausal hormone therapy use were enrolled at a clinic in Western NY in 2005. Urinary estrogens and estrogen metabolites were measured using mass spectrometry. Percent MD and dense area (cm(2)) were measured using computer-assisted analyses of digitized films. Linear regression models were used to estimate associations of log-transformed estrogen measures with MD while adjusting for age, body mass index (BMI), parity, and past hormone therapy use.


RESULTS
Urinary concentrations of most individual estrogens and metabolites were not associated with MD; however, across the interdecile range of the ratio of parent estrogens (estrone and estradiol) to their metabolites, MD increased by 6.8 percentage points (P = 0.02) and dense area increased by 10.3 cm(2) (P = 0.03). Across the interdecile ranges of the ratios of 2-, 4-, and 16-hydroxylation pathways to the parent estrogens, MD declined by 6.2 (P = 0.03), 6.4 (P = 0.04), and 5.7 (P = 0.05) percentage points, respectively. All associations remained apparent in models without adjustment for BMI.


CONCLUSIONS
In this study of postmenopausal women, less extensive hydroxylation of parent estrogens was associated with higher MD.


CONCLUSIONS
Hydroxylation of estrogens may modulate postmenopausal breast cancer risk through a pathway involving MD.
Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, USA. fuhrmanb@mail.nih.gov
Barbara J
BJ
Fuhrman
Louise A
LA
Brinton
Ruth M
RM
Pfeiffer
Xia
X
Xu
Timothy D
TD
Veenstra
Barbara E
BE
Teter
Celia
C
Byrne
Cher M
CM
Dallal
Maddalena
M
Barba
Paola C
PC
Muti
Gretchen L
GL
Gierach
D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D016014:Linear Models; D008327:Mammography; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*
D004967:Estrogens