Dr. Ron’s Research Review – August 1, 2012

This week’s research review focuses on breast cancer and urinary hormones.

A recent study examined urine samples of 86 postmenopausal female breast cancer patients and 36 healthy controls. The parent estrogens, estrone (E1) and 17beta-estradiol (E2), as well as 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2) were produced in higher abundance, whereas 16alpha-hydroxyestrone (16alpha-OHE1) and 2-methoxyestradiol (2-MeOE2) were decreased in the breast cancer group. 2-OHE2 and 4-OHE2 in particular showed significant elevation in patients, which are consistent with the carcinogenic mechanism hypothesis that catechol estrogens can react with DNA via quinones, resulting in mutations to induce breast cancer. Thus, 2,4-hydroxylation may be the dominant metabolic pathway for parent estrogens rather than 16alpha-hydroxylation. The lower level of 2-MeOE2 in the breast cancer group was believed to correlate with its protective effect against tumor formation. (Huang, Sun et al. 2012

Dr. Ron


Abstract

Analysis of multiplex endogenous estrogen metabolites in human urine using ultra-fast liquid chromatography-tandem mass spectrometry: a case study for breast cancer

            (Huang, Sun et al. 2012) Download

A rapid, sensitive, specific and accurate analytical method of ultra-fast liquid chromatography combined with tandem mass spectrometry (UFLC-MS/MS) was established for simultaneous quantitative analysis of 16 distinct endogenous estrogens and their metabolites (EMs) in postmenopausal female urine. The quantitative method utilized a hydrolysis/extraction/derivatization step and a UFLC system to achieve separation in 16 min. The lower limit of quantitation for each estrogen metabolite was 2 pg mL(-1) with the percent recovery of a known added amount of estrogen at 93.2-109.3%. The intra-batch accuracy and precision for all analytes were 87.5-107.7% and 0.6-11.7%, respectively, while inter-batch accuracy and precision were 87.0-105.8% and 1.2-10.2%, respectively. Using this developed and validated method, the comprehensive metabolic profiling of 16 EMs in urine samples of 86 postmenopausal female breast cancer patients and 36 healthy controls was investigated by systematic statistical analysis. As a result, the circulating levels of 6 EMs were found to be different by a comparison of patients and healthy controls. The parent estrogens, estrone (E1) and 17beta-estradiol (E2), as well as 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2) were produced in higher abundance, whereas 16alpha-hydroxyestrone (16alpha-OHE1) and 2-methoxyestradiol (2-MeOE2) were decreased in the breast cancer group. 2-OHE2 and 4-OHE2 in particular showed significant elevation in patients, which are consistent with the carcinogenic mechanism hypothesis that catechol estrogens can react with DNA via quinones, resulting in mutations to induce breast cancer. Thus, 2,4-hydroxylation may be the dominant metabolic pathway for parent estrogens rather than 16alpha-hydroxylation. The lower level of 2-MeOE2 in the breast cancer group was believed to correlate with its protective effect against tumor formation. This study could provide valuable information on the association of the EM metabolic pathway with carcinogenesis as well as identify potential biomarkers for estrogen-induced breast cancer risk.

References

Huang, J., J. Sun, et al. (2012). "Analysis of multiplex endogenous estrogen metabolites in human urine using ultra-fast liquid chromatography-tandem mass spectrometry: a case study for breast cancer." Anal Chim Acta 711: 60-8.