Circulating Estrogen Metabolites and Risk for Breast Cancer in Premenopausal Women

Arslan, Alan A.; Shore, Roy E.; Afanasyeva, Yelena; Koenig, Karen L.; Toniolo, Paolo; Zeleniuch‐Jacquotte, Anne

doi:10.1158/1055-9965.epi-09-0312

Cited by 32 publications

(41 citation statements)

References 44 publications

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“…The New York University Women’s Health Study [138] is the only trial that has reported circulating levels of the 2/16-hydroxyestrone ratio. In this study, 377 cases were matched with 377 controls on day and phase of menstrual cycle.…”

Section: Estrogens and Breast Cancer Riskmentioning

confidence: 99%

Estrogen metabolism and breast cancer

2015

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There is currently accumulating evidence that endogenous estrogens play a critical role in the development of breast cancer. Estrogens and their metabolites have been studied in both pre- and postmenopausal women with more consistent results shown in the latter population, in part because of large hormonal variations during the menstrual cycle and far fewer studies having been performed in premenopausal women. In this review we describe in detail estrogen metabolism and associated genetic variations, and provide a critical review of the current literature regarding the role of estrogens and their metabolites in breast cancer risk.

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Section: Estrogens and Breast Cancer Riskmentioning

confidence: 99%

Estrogen metabolism and breast cancer

2015

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“…Results continued to be inconsistent. In the New York University Women’s Health Study (NYUWHS) cohort, the positive association with the ratio was noticeably stronger for estrogen receptor-positive (ER+) tumors in premenopausal women but became inverse for ER+ tumors in postmenopausal women (in premenopausal women, adjusted RR across extreme quartiles of ratio=2.15; 95% CI=0.9 to 5.3 for ER+ and 1.18; 95% CI=0.2 to 6.5 for estrogen receptor-negative (ER−) tumors; in postmenopausal women, adjusted RR for doubling of ratio=0.81; 95% CI=0.6 to 1.1 for ER+ and 1.17, 95% CI=0.5 to 2.6 for ER− tumors) [21,23]. In the Nurses’ Health Study (NHS) cohort also, adjusted relative risk across extreme quartiles of the ratio became inverse for postmenopausal ER+ progesterone receptor-positive (PR+) breast cancer (RR=0.88; 95% CI=0.5 to 1.5) [20].…”

Section: Prospective Studies Of 2-hydroxyestrone 16α-hydroxyestronementioning

confidence: 99%

Epidemiologic studies of estrogen metabolism and breast cancer

et al. 2015

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Early epidemiologic studies of estrogen metabolism measured only 2-hydroxyestrone and 16α-hydroxyestrone and relied on direct enzyme immunoassays without purification steps. Eight breast cancer studies have used these assays with prospectively collected blood or urine samples. Results were inconsistent, and generally not statistically significant; but the assays had limited specificity, especially at the low concentrations characteristic of postmenopausal women. To facilitate continued testing in population-based studies of the multiple laboratory-based hypotheses about the roles of estrogen metabolites, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed to measure concurrently all 15 estrogens and estrogen metabolites in human serum and urine, as unconjugated and total (glucuronidated+sulfated+unconjugated) concentrations. The assay has high sensitivity (lower limit of quantitation ~1–2 pmol/L), reproducibility (coefficients of variation generally ≤5%), and accuracy. Three prospective studies utilizing this comprehensive assay have demonstrated that enhanced 2-hydroxylation of parent estrogens (estrone+estradiol) is associated with reduced risk of postmenopausal breast cancer. In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort, the serum ratio of 2-hydroxylation pathway metabolites to parent estrogens was associated with a 28% reduction in breast cancer risk across extreme deciles (p-trend=.05), after adjusting for unconjugated estradiol and breast cancer risk factors. Incorporating this ratio into a risk prediction model already including unconjugated estradiol improved absolute risk estimates substantially (by ≥14%) in 36% of the women, an encouraging result that needs replication. Additional epidemiologic studies of the role of estrogen metabolism in the etiology of hormone-related diseases and continued improvement of estrogen metabolism assays are justified.

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“…Estrogen has been confirmed to be a carcinogen for breast cancer. higher levels of estrogens in the plasma and urine are thought to be associated with human breast cancer (23)(24)(25)(26). The relationship between higher levels of estrogens and fat diet has been explored by several researchers; however, epidemiological studies have shown conflicting results regarding an association of dietary fat with breast cancer.…”

Section: Discussionmentioning

confidence: 99%

In vitro transformation of MCF-10A cells by sera harvested from heifers two months post-Zeranol implantation

Xu²,

Zhong³

et al. 2011

Int J Oncol

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Abstract. Among many risk factors of breast cancer, estrogens and non-estrogenic endocrine disruptors are considered to play critical roles in human breast carcinogenesis. Zeranol (Z) is a non-steroidal agent with potent estrogenic activity and has been widely used as an FDA approved beef growth promoter in the US. Recently, concerns have been raised about the potential adverse health risk by consumption of products containing biologically active Z and its metabolites. By utilizing cell proliferation assay, soft agar assay, quantitative real-time PCR and Western blotting analysis, we examined the potentially tumorigenic activity of bio-active Z containing sera harvested from heifers two months post Z-implantation and the underlying mechanisms. Our results showed that the growth of MCF-10A exposed to 0.2, 1 and 5% Z-containing serum (ZS) treatment for 3 weeks was 1.3, 1.75 and 1.8-fold faster compared to that of the control sera. After further investigation, we found that ZS increased cyclin D1 and decreased p53 expression at the mRNA and protein levels in MCF-10A compared to the controls. More importantly, treatment of 1% Z-containing sera for 21 days stimulated MCF-10A cells anchorage-independent colony formation in soft agar which illustrates its capability of inducing human normal breast epithelial cell neoplastic transformation. Our experimental results suggest that longterm exposure of low levels of Z and its metabolites contained in beef products might be a potential risk factor in human breast cancer initiation and development.

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Circulating Estrogen Metabolites and Risk for Breast Cancer in Premenopausal Women

Cited by 32 publications

References 44 publications

Estrogen metabolism and breast cancer

Estrogen metabolism and breast cancer

Epidemiologic studies of estrogen metabolism and breast cancer

In vitro transformation of MCF-10A cells by sera harvested from heifers two months post-Zeranol implantation

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