Faculty Opinions recommendation of The effect of tamoxifen and raloxifene on estrogen metabolism and endometrial cancer risk
Abstract
Selective estrogen receptor modulators (SERMs) demonstrate differential endometrial cancer (EC) risk.While tamoxifen (TAM) use increases the risk of endometrial hyperplasia and malignancy, raloxifene (RAL) has neutral effects on the uterus.How TAM increases the risk of EC and why TAM and RAL differentially modulate the risk for EC, however, remain elusive.Here, we tested the hypothesis that TAM increases the risk for EC, at least in part, by enhancing the local estrogen biosynthesis and directing estrogen metabolism towards the formation of genotoxic and hormonally active estrogen metabolites.In addition, the differential effects of TAM and RAL in EC risk are attributed to their differential effect on estrogen metabolism/metabolites.The endometrial cancer cell line (Ishikawa cells) and the non-malignant immortalized human endometrial glandular cell line (EM1) were used for the study.The profile of estrogen/estrogen metabolites (EM), depurinating estrogen-DNA adducts, and the expression of estrogenmetabolizing enzymes in cells treated with 17β-estradiol (E2) alone or in combination with TAM or RAL were investigated using high performance liquid chromatography-electrospray ionizationtandem mass spectrometry (HPLC-ESI-MS 2 ), ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS), and Western blot analysis, respectively.TAM significantly increased the total EM and enhanced the formation of hormonally active and carcinogenic estrogen metabolites,…
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Evidence Hub reads this as a review, done in cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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