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- W4362568442 abstract "<div>Abstract<p>Five years of tamoxifen reduces breast cancer risk by nearly 50% but is associated with significant side effects and toxicities. A better understanding of the direct and indirect effects of tamoxifen in benign breast tissue could elucidate new mechanisms of breast carcinogenesis, suggest novel chemoprevention targets, and provide relevant early response biomarkers for phase II prevention trials. Seventy-three women at increased risk for breast cancer were randomized to tamoxifen (20 mg daily) or placebo for 3 months. Blood and breast tissue samples were collected at baseline and posttreatment. Sixty-nine women completed all study activities (37 tamoxifen and 32 placebo). The selected biomarkers focused on estradiol and IGFs in the blood; DNA methylation and cytology in random periareolar fine-needle aspirates; and tissue morphometry, proliferation, apoptosis, and gene expression (microarray and reverse transcriptase PCR) in the tissue core samples. Tamoxifen downregulated <i>Ets</i> oncogene transcription factor family members ETV4 and ETV5 and reduced breast epithelial cell proliferation independent of <i>CYP2D6</i> genotypes or effects on estradiol, ESR1, or IGFs. Reduction in proliferation was correlated with downregulation of ETV4 and DNAJC12. Tamoxifen reduced the expression of <i>ETV4-</i> and <i>ETV5-</i>regulated genes implicated in epithelial-stromal interaction and tissue remodeling. Three months of tamoxifen did not affect breast tissue composition, cytologic atypia, preneoplasia, or apoptosis. A plausible mechanism for the chemopreventive effects of tamoxifen is restriction of lobular expansion into stroma through downregulation of <i>ETV4</i> and <i>ETV5</i>. The human equivalent of murine multipotential progenitor cap cells of terminal end buds may be the primary target. <i>Cancer Prev Res; 4(11); 1852–62. ©2011 AACR</i>.</p></div>" @default.
- W4362568442 created "2023-04-06" @default.
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- W4362568442 date "2023-04-03" @default.
- W4362568442 modified "2023-10-16" @default.
- W4362568442 title "Data from Tamoxifen Downregulates <i>Ets</i> Oncogene Family Members <i>ETV4</i> and <i>ETV5</i> in Benign Breast Tissue: Implications for Durable Risk Reduction" @default.
- W4362568442 doi "https://doi.org/10.1158/1940-6207.c.6544613" @default.
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