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Objective: Risk-reducing therapy with selective estrogen receptor (ER) modulators and aromatase inhibitors reduce breast cancer risk. However, the effects are limited to ER-positive breast cancer. Therefore, new agents with improved toxicity profiles that reduce the risk in ER-negative breast cancers are urgently needed. The aim of this prospective, short-term, prevention study was to evaluate the effect of dasatinib, an inhibitor of the tyrosine kinase Src, on biomarkers in normal (but increased risk) breast tissue and serum of women at high risk for a second, contralateral primary breast cancer. Materials and Methods: Women with a history of unilateral stage I, II, or III ER-negative breast cancer, having no active disease, and who completed all adjuvant therapies were eligible. Patients underwent baseline fine-needle aspiration (FNA) of the contralateral breast and serum collection for biomarker analysis and were randomized to receive either no treatment (control) or dasatinib at 40 or 80 mg/day for three months. After three months, serum collection and breast FNA were repeated. Planned biomarker analysis consisted of changes in cytology and Ki-67 on breast FNA, and changes in serum levels of insulin-like growth factor 1 (IGF-1), IGF-binding protein 1, and IGF-binding protein 3. The primary objective was to evaluate changes in Ki-67 and secondary objective included changes in cytology in breast tissue and IGF-related serum biomarkers. Toxicity was also evaluated. Results: Twenty-three patients started their assigned treatments. Compliance during the study was high, with 86.9% (20/23) of patients completing their assigned doses. Dasatinib was well tolerated and no drug-related grade 3 and 4 adverse events were observed. Since only one patient met the adequacy criteria for the paired FNA sample, we could not evaluate Ki-67 level or cytological changes. No significant change in serum biomarkers was observed among the three groups. Conclusion: Dasatinib was well tolerated but did not induce any significant changes in serum biomarkers. The study could not fulfill its primary objective due to an inadequate number of paired FNA samples. Further, larger studies are needed to evaluate the effectiveness of Src inhibitors in breast cancer prevention. [ABSTRACT FROM AUTHOR]

Aberrant expression of human leukocyte antigen G (HLA-G), an immunosuppressive molecule, has been observed in various cancer types. The exact mechanism of HLA-G expression is unclear. HLA-G expression is associated with low expression levels of microRNA (miR)-148a and miR-152. To the best of our knowledge, the prognostic value of the expression levels of miR-148a, miR-152 and HLA-G has not been investigated in colon cancer. The aim of the present study was to investigate the relationship between the presence of HLA-G molecules and the expression levels of miR-148 and miR-152 in colon cancer. In addition, the association of both HLA-G and miR expression with survival results and clinicopathological data was determined. An immunohistochemical method was used for detection of HLA-G expression in the tumor tissues and adjacent healthy tissues of 108 patients with colon cancer. Reverse transcription-quantitative PCR was used for miR analysis. HLA-G was expressed in 82 (75.9%) of the cancer samples, and there was no staining in normal tissues. HLA-G expression >20%, which was found in 41.7% (45/108) of the patients with colon cancer, was significantly positively associated with patient survival (P=0.039). Additionally, miR-148a levels were lower in the tumor tissues compared with the adjacent healthy tissues. No differences were found for miR-152 expression. In addition, mir-148a levels were found to be significantly lower (P=0.001) in HLA-G-positive tumor tissues than HLA-G-negative tumor tissues, but no such relationship was found for miR-152 levels. The presence of HLA-G expression was associated with poor survival outcomes. HLA-G is one of the prognostic factors in colon cancer, and decreased miR-148a expression in colon cancer tissues may be associated with HLA-G-mediated carcinogenesis. [ABSTRACT FROM AUTHOR]