Estrogen metabolism and breast cancer.
BACKGROUND
Specific pathways involved in estrogen metabolism may play a role in the etiology of breast cancer. We used data from a large population-based case-control study to assess the association of the urinary estrogen metabolites 2-hydroxyestrone (2-OHE1), 16alpha-hydroxyestrone (16-OHE1), and their ratio (2/16) with both invasive and in situ breast cancer.


METHODS
Study participants from the Long Island Breast Cancer Study Project provided a spot urine specimen and completed a comprehensive interviewer-administered questionnaire. Women who used exogenous hormones or who took tamoxifen in the 6 months before urine collection were excluded from the analysis, leaving 269 invasive cases, 158 in situ cases, and 326 controls. Unconditional logistic regression was used to obtain adjusted odds ratios (ORs) for invasive and in situ breast cancer, separately, in relation to tertiles of the individual metabolites (standardized for creatinine) and the 2/16 ratio, stratified by menopausal status.


RESULTS
The OR for invasive breast cancer was inversely associated with the 2/16 ratio among premenopausal women (OR = 0.50 for extreme tertiles; 95% confidence interval = 0.25-1.01). ORs ranged from 0.32 to 0.60 when women were stratified by whether cases had received chemotherapy within 6 months before urine collection and by estrogen receptor status. In postmenopausal women, there was a slight reduction in the odds ratio for invasive cancer with high levels of the 2/16 ratio (OR = 0.78; 95% confidence interval = 0.46-1.33). Neither the individual metabolites nor the ratio were associated with in situ breast cancer.


CONCLUSIONS
These data provide support for the hypothesis that the 2/16 ratio is associated with reduced breast cancer risk. The most consistent associations were observed with invasive cancer in premenopausal women.
Kabat
Geoffrey C
GC
Department of Preventive Medicine, School of Medicine, Stony Brook University, New York, USA. gck1@optonline.net
O'Leary
Erin S
ES
Gammon
Marilie D
MD
Sepkovic
Daniel W
DW
Teitelbaum
Susan L
SL
Britton
Julie A
JA
Terry
Mary B
MB
Neugut
Alfred I
AI
Bradlow
H Leon
HL
D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000652:urine; D016022:Case-Control Studies; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000652:urine; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009518:New York / Q000453:epidemiology; D011795:Surveys and Questionnaires
D004967:Estrogens; D006894:Hydroxyestrones; C026702:16-hydroxyestrone; C024980:2-hydroxyestrone