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Previously, the effect of 2\u2010ME on early\u2010 and late\u2010stage breast cancer (BC) was investigated in vivo using a transgenic mouse model (FVB\/N\u2010Tg(MMTV\u2010PyVT)) of spontaneous mammary carcinoma. Anti\u2010tumor effects were observed in late\u2010stage BC with no effect on early\u2010stage BC. Given the contrasting results obtained from the different BC stages, we have now investigated the effect of 2\u2010ME when administered before the appearance of palpable tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Each mouse received 100\u2009mg\/kg 2\u2010ME on day 30 after birth, twice per week for 28\u2009days, while control mice received vehicle only. Animals were terminated on day 59. Lung and mammary tissue were obtained for immunohistochemical analysis of CD163 and CD3 expression, and histological examination was performed to analyze tumor necrosis. Additionally, blood samples were collected to measure plasma cytokine levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>2\u2010ME increased tumor mass when compared to the untreated animals (<jats:italic>p<\/jats:italic>\u2009=\u2009.0139). The pro\u2010tumorigenic activity of 2\u2010ME was accompanied by lower CD3+ T\u2010cell numbers in the tumor microenvironment (TME) and high levels of the pro\u2010inflammatory cytokine interleukin (IL)\u20101\u03b2. Conversely, 2\u2010ME\u2010treatment resulted in fewer CD163+ cells detectable in the TME, increased levels of tumor necrosis, increased IL\u201010 plasma levels, and low IL\u20106 and IL\u201027 plasma levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Taken together, these findings suggest that 2\u2010ME promotes early\u2010stage BC development.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.2068","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T02:55:51Z","timestamp":1712804151000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of 2\u2010methoxyestradiol on mammary tumor initiation and progression"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-2096","authenticated-orcid":false,"given":"Kimberly T.","family":"Peta","sequence":"first","affiliation":[{"name":"Department of Immunology, Institute for 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