Akt1 overexpression in HER2/neu positive breast tumors in African American and Latina women may contribute to poor disease free and overall survival Free

B104

Breast cancer patients with HER2/neu overexpressing tumors have a decrease in disease free survival and overall survival. It remains to be understood, what the etilology of HER2/neu overexpressing breast tumors is in African American and Latina women. These groups generally have a poorer outcome from their breast cancer compared to Caucasian and Asian women. The purpose of this study is to understand the clinical significance of activated Akt expression in breast tumors from African American and Latina patients with corresponding tissue HER2/neu over-expression. Cellular and molecular studies have shown that activation of the cell signaling PI3-kinase/Akt cascade via the HER2/neu and other receptor tyrosine kinases induce cell proliferation. A total 234 African American and Latina patients were selected retrospectively. From this group, 120 tumor tissue samples were analyzed for tissue pAkt by immunohistochemistry. This cohort consisted of 59 HER2/neu positive and 61 HER2/neu negative tumors and these numbers gave the study 80% power with 95% confidence limit. The predictive value of activated tissue Akt in relation to HER2/neu over-expression for disease free survival was determined. Our results demonstrate that increase in pAkt was significantly associated with HER2/neu positive and estrogen/progesterone receptor (ER/PR) negative breast tumor. The activation of Akt was associated with positive lymph nodes. These patients were less responsive to tamoxifen and/or chemotherapy. Activation of Akt significantly reduced DFS in both HER2/neu positive and negative groups. However, the DFS was similar between HER2/neu-positive/pAkt-negative and HER2/neu-negativer/pAkt-positve groups. In summary, our data suggest that there may be differences in tumor phenotypes within the HER2/neu over-expressing breast cancer patients. The over-expression of pAkt may be a powerful prognostic marker for breast cancer relapse.