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Review
. 2015 Jan 28;356(2 Pt A):231-43.
doi: 10.1016/j.canlet.2014.04.018. Epub 2014 Apr 28.

Estrogen metabolism and breast cancer

Hamed Samavat  1 , Mindy S Kurzer  2
Affiliations
Review

Estrogen metabolism and breast cancer

Hamed Samavat et al. Cancer Lett. .

Abstract

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.

Keywords: Breast cancer; Estrogen; Estrogen metabolites; Postmenopausal women; Premenopausal women; Sex hormones.

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Conflict of interest statement

Conflict of Interest

None of the authors has a conflict of interest.

Figures

Figure 1
Figure 1. Pathways of steroid hormone synthesis in humans
Abbreviations: StAR, steroidogenic acute regulatory protein; CYP11A1, side-chain cleavage of P450; CYP17A1, 17-hydroxylase/17,20-lyase; HSD3B2, 3β-hydroxysteroid dehydrogenase-Δ5,4 isomerase type 2; ; CYP19A1, aromatase; HSD17B1, 17β-hydroxysteroid dehydrogenase type 1 [13].
Figure 2
Figure 2. Endogenous estrogen metabolism in human
The parent estrogens estrone and estradiol are reversibly inter-converted, catalyzed by the 17β-hydroxysteroid dehydrogenase enzyme. They are also converted to catechol estrogens including 2-hydroxestrogens, 4-hydroxestrogens, 16-hydroxestrone, or estriol through the action of CYP enzymes. Catechol estrogens, in turn, are metabolized to 2-methoxyestrogens and 4-methoxyestrogens. Estrone, catechol estrogens, and methoxyestrogens can be conjugated to glucuronic acid and sulfate. Abbreviations: COMT, catechol-O-methyltransferase; CYP, cytochrome P-450 enzyme [114].
Figure 3
Figure 3. Estradiol metabolism and DNA adduct formation
Estradiol catechol estrogens, including 2-hydroxyestradiol and 4-hydroxyestradiol, can go through reductive-oxidative cycling and produce mutagenic free radicals. These reactions are catalyzed by CYP and peroxidase enzymes. Estrogen semiquinones and quinones are reactive and carcinogenic intermediate metabolites of redox cycling pathways and can cause DNA damage. Abbreviations: CYP, cytochrome P-450 enzyme; COMT, catechol-O-methyltransferase [17].
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