Sergio Aguggini
Breast Cancer Unit-Women’s Centre- ASST of Cremona,Italy
Title: Hypoxia-related biological markers as predictors of epirubicin-based treatment responsiveness and resistance in locally advanced breast cancer
Biography
Biography: Sergio Aguggini
Abstract
Because hypoxia mediates resistance to anthracyclines in vitro, we aimed to identify hypoxia-related biological markers involved in the response and resistance to epirubicin in patients with locally advanced breast cancer. One hundred seventy-six women with T2-4 N0-1 breast tumors were randomly assigned to receive epirubicin 120 mg/m2/1-21 (EPI ARM), epirubicin 120 mg/m2/1-21 + erythropoietin 10.000 IU sc three times weekly (EPI-EPO ARM) and epirubicin 40 mg/m2/w-q21 (EPI-W ARM). Sixteen tumor proteins involved in cell survival, hypoxia, angiogenesis and growth factor, were assessed by immunohistochemistry in pre-treatment samples and a multivariate generalized linear regression approach was applied using a penalized least-square minimization to perform variable selection and regularization. Ten-fold cross-validation and iterative leave-one-out were employed to validate and test the model, respectively. High VEGF and GLUT-1 and low ER were significant factors for complete clinical response to treatment in all leave-one-out iterations. EPO expression was positively correlated with pCR. High HB levels, bcl-2 and HIF-1 expression were significantly negatively correlated with pCR, HB baseline level and HIF-1 alpha nuclear expression were significantly positively associated with a higher risk of relapse and with overall survival.