Abstract

<div>Abstract<p>We have generated DNA methylation profiles of 148 human breast tumors and found significant differences in hormone receptor (HR) status between clusters of DNA methylation profiles. Of 35 DNA methylation markers analyzed, the <i>ESR1</i> gene, encoding estrogen receptor α, proved to be the best predictor of progesterone receptor status, whereas methylation of the <i>PGR</i> gene, encoding progesterone receptor, was the best predictor of estrogen receptor status. <i>ESR1</i> methylation outperformed HR status as a predictor of clinical response in patients treated with the antiestrogen tamoxifen, whereas promoter methylation of the <i>CYP1B1</i> gene, encoding a tamoxifen- and estradiol-metabolizing cytochrome P450, predicted response differentially in tamoxifen-treated and nontamoxifen-treated patients. High levels of promoter methylation of the <i>ARHI</i> gene, encoding a RAS-related small G-protein, were strongly predictive of good survival in patients who had not received tamoxifen therapy. Our results reveal an as yet unrecognized degree of interaction between DNA methylation and HR biology in breast cancer cells and suggest potentially clinically useful novel DNA methylation predictors of response to hormonal and non-hormonal breast cancer therapy.</p></div>

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