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This study sought to investigate whether oral iron-saturated bovine lactoferrin (Fe-Lf), a natural product which enhances chemotherapy, could improve the chemotherapeutic effects of tamoxifen in the treatment of ER-negative breast cancers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In a model of breast cancer prevention, female Balb\/c mice treated with tamoxifen (5\u2009mg\/Kg) were fed an Fe-Lf supplemented diet (5\u2009g\/Kg diet) or the base diet. At week 2, 4T1 mammary carcinoma cells were injected into an inguinal mammary fat pad. In a model of breast cancer treatment, tamoxifen treatment was not started until two weeks following tumor cell injection. Tumor growth, metastasis, body weight, and levels of interleukin 18 (IL-18) and interferon \u03b3 (IFN-\u03b3) were analyzed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Tamoxifen weakly (IC<jats:sub>50<\/jats:sub>\u2009~\u20098\u2009\u03bcM) inhibited the proliferation of 4T1 cells at pharmacological concentrations <jats:italic>in vitro<\/jats:italic>. In the tumor prevention study, a Fe-Lf diet in combination with tamoxifen caused a 4\u2009day delay in tumor formation, and significantly inhibited tumor growth and metastasis to the liver and lung by 48, 58, and 66% (all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), respectively, compared to untreated controls. The combination therapy was significantly (all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) more effective than the respective monotherapies. Oral Fe-Lf attenuated the loss of body weight caused by tamoxifen and cancer cachexia. It prevented tamoxifen-induced reductions in serum levels of IL-18 and IFN-\u03b3, and intestinal cells expressing IL-18 and IFN-\u03b3. It increased the levels of Lf in leukocytes residing in gut-associated lymphoid tissues. B, T and Natural killer (NK) cells containing high levels of Lf were identified in 4T1 tumors, suggesting they had migrated from the intestine. Similar effects of Fe-Lf and tamoxifen on tumor cell viability were seen in the treatment of established tumors.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The results indicate that Fe-Lf is a potent natural adjuvant capable of augmenting the chemotherapeutic activity of tamoxifen. It could have application in delaying relapse in tamoxifen-treated breast cancer patients who are at risk of developing ER-negative tumors.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-12-591","type":"journal-article","created":{"date-parts":[[2012,12,11]],"date-time":"2012-12-11T15:14:11Z","timestamp":1355238851000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["\u201cIron-saturated\u201d bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice"],"prefix":"10.1186","volume":"12","author":[{"given":"Xueying","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruohan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aneta","family":"Przepiorski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiva","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate P","family":"Palmano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey W","family":"Krissansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,12,11]]},"reference":[{"key":"3586_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3322\/caac.20107","volume":"61","author":"A Jemal","year":"2011","unstructured":"Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. 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