Dr. Ron’s Research Review – September 18, 2013

© 2013

This week’s research review focuses on 2ME2 and breast cancer risk.

A National Cancer Institute study published in Breast Cancer Research examined the relationship of serum estrogens and estrogen metabolites to postmenopausal breast cancer risk. (Falk, Brinton et al. 2013)

Between 1977 and 1987, 6915 women provided blood samples to the Columbia Missouri Serum Bank and were followed for incident breast cancer through December 2002. 215 postmenopausal breast cancer cases were compared with 215 matched controls that were not using exogenous hormones at the time of blood draw.

Risks for the highest levels of two estrogen metabolites were significantly decreased. The odds ratio (OR) were:

2-methoxyestradiol

0.53

95% CI=0.30-0.96

2-hydroxyestrone-3-methyl ether

0.57

95% CI=0.33-0.99

These findings suggest that women with more extensive estrogen metabolism along the 2-hydroxylation pathway may have a reduced risk of postmenopausal breast cancer.

Dr. Ron


Articles

Relationship of serum estrogens and estrogen metabolites to postmenopausal breast cancer risk: a nested case-control study

         (Falk, Brinton et al. 2013) Download

INTRODUCTION: Elevated levels of circulating estrogens are linked to breast cancer risk among postmenopausal women but little is known about the importance of estrogen metabolism. A recently developed liquid chromatography tandem mass spectrometry-based method (LC-MS/MS) measuring a panel of 15 estrogen metabolites (EM) has been evaluated in one study, linking high levels of 2-pathway metabolites relative to the parent estrogens to reduced breast cancer risk. We analyzed this panel of EM in a nested case-control study of postmenopausal breast cancer. METHODS: Between 1977 and 1987, 6915 women provided blood samples to the Columbia Missouri Serum Bank and were followed for incident breast cancer through December 2002. We studied 215 postmenopausal breast cancer cases and 215 matched controls that were postmenopausal and not using exogenous hormones at the time of blood draw. EM were examined individually, grouped by pathway (hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring), and by ratios of the groupings. Logistic regression models controlling for matching and breast cancer risk factors were used to calculate quartile-specific odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Significant elevated risks were not observed for individual EM, except for quartiles of 16-epiestriol (p trend =0.07). OR for total EM, the parent estrogens estrone and estradiol, and 2-pathway catechol EM (2-hydroxyestrone and 2-hydroxyestradiol) were elevated but trends were not statistically significant. Among 2-pathway metabolites, risks for the highest levels of 2-hydroxyestrone-3-methyl ether, and 2-methoxyestradiol were reduced; ORs for women in the highest vs. lowest quartiles were 0.57 (95% CI=0.33-0.99) and 0.53 (95% CI=0.30-0.96), respectively. Overall, women with higher levels of 2-pathway EM had a reduced risk of breast cancer, which remained after accounting for levels of parent EM, 4-pathway EM, and 16-pathway EM (all trends, p<0.11). CONCLUSIONS: Women with more extensive hydroxylation along the 2-pathway may have a reduced risk of postmenopausal breast cancer. Further studies are needed to clarify the risks for specific EM and complex patterns of estrogen metabolism. This will require aggregation of EM results from several studies.


References

Falk, R. T., L. A. Brinton, et al. (2013). "Relationship of serum estrogens and estrogen metabolites to postmenopausal breast cancer risk: a nested case-control study." Breast Cancer Res 15(2): R34. [PMID: 23607871]