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Endocrine and Oncologic Surgery Research Lab
Harrison Department of Surgical Research
Brian J. Czerniecki, M.D., Ph.D.
 

Evaluating the Role of HER-2/neu
in Breast Cancer Development

 
We are interested in defining the role of HER-2/neu in breast cancer development. While HER-2/neu is over-expressed in about 25% of IBC HER-2/neu expression is found in about 50-60% of high grade DCIS lesions. It has never been clear why this disparity in HER-2/neu expression exists between DCIS and IBC. We hypothesized that HER-2/neu expression in DCIS may be critical to the development of early breast cancer and less important in IBC that could account for the greater expression in DCIS compared to IBC. We assessed the expression of HER-2/neu in DCIS lesions where obvious IBC was excluded by breast MRI to determine whether HER-2/neu expressing DCIS was associated with the development of early invasive breast cancer. We demonstrated in a multivariate analysis that HER-2/neu over-expression in DCIS was highly associated with the finding of early invasive breast cancer Roses et. al Cancer Epidemol Biomarkers Prevention 18:1386-89, 2009. While high grade and large tumor size and HER-2/neu expression were associated with the development of invasion only HER-2/neu expression was independently associated with the presence of IBC in patients with DCIS. The combination of both estrogen receptor expression and HER-2/neu expression was associated with the finding of invasive foci in DCIS in about 50% of cases. A second manuscript has been submitted describing the instability of this phenotype between the DCIS expression and the invasive phenotype. Additional studies are planned to assess the molecular phenotypes of the DCIS and IBC to determine whether HER-2/neu expression is causal in the development of IBC as this would have obvious clinical implications for targeting HER-2/neu to prevent the transition from DCIS to IBC.
 

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