URINARY ESTROGEN METABOLITES AND BREAST-CANCER - A CASE-CONTROL STUDY

Preliminary studies suggest that the estrogen metabolite 16 alpha-hydr oxyestrone is associated with breast cancer, whereas 2-hydroxyestrone is not, However, epidemiological studies evaluating this relationship and taking established risk factors for breast cancer into account are lacking, The purpose of this study was to examine the association of the ratio of the urinary estrogen metabolites (2-hydroxyestrone and 16 alpha-hydroxyestrone) and of the individual metabolites with breast c ancer, A spot urine sample, a brief history, and clinical data were co llected from breast cancer cases (ii = 42) and from women coming to th e hospital for a routine mammogram or attending a free breast cancer s creening (n = 64), 2-Hydroxyestrone and 16 alpha-hydroxyestrone were m easured by enzyme immunoassay, and the estrogen metabolite ratio (EMR; 2-hydroxyestrone:16 alpha-hydroxyestrone) was computed, Cases and con trols were similar in terms of age (mean age of cases, 53.8 +/- 15.1 y ears, versus 54.2 +/- 10.4 years for controls; P = 0.9) and demographi cs, Mean EMR was not associated with breast cancer overall (1.67 +/- 0 .80 versus 1.72 +/- 0.66; P = 0.7), However, in postmenopausal women, the mean EMR was significantly lower in cases compared to controls (1. 41 +/- 0.73 versus 1.81 +/- 0.71; P = 0.05), The multivariate adjusted odds ratios for the intermediate and lowest tertiles of the EMR relat ive to the highest among postmenopausal women were 9.73 (95% confidenc e interval, 1.27-74.84) and 32.74 (95% confidence interval, 3.36-319.0 9), respectively, The test for trend was highly significant (P = 0.003 ), Analyses of the individual metabolites indicated that 16 alpha-hydr oxyestrone was a strong risk factor, The EMR did not show any consiste nt associations with age, race/ethnicity, age at first birth, parity, body mass index, family history of breast cancer, smoking, or alcohol intake. These data suggest a strong, inverse association of the EMR an d a strong positive association of 16 alpha-hydroxyestrone with breast cancer in postmenopausal women, Larger studies are needed to confirm these results and to assess the relationship of the EMR and of the ind ividual metabolites with breast cancer, with attention to menopausal s tatus and clinical factors and with adjustment for known breast cancer risk factors.