51. Hypoxia-related biological markers as predictors of epirubicin-based treatment responsiveness and resistance in locally advanced breast cancer
- Author
-
Milani, M, Venturini, S, Bonardi, S, Allevi, G, Strina, C, Cappelletti, MR, Corona, SP, Aguggini, S, Bottini, A, Berruti, A, Jubb, A, Campo, L, Harris, AL, Gatter, K, Fox, SB, Generali, D, Roviello, G, Milani, M, Venturini, S, Bonardi, S, Allevi, G, Strina, C, Cappelletti, MR, Corona, SP, Aguggini, S, Bottini, A, Berruti, A, Jubb, A, Campo, L, Harris, AL, Gatter, K, Fox, SB, Generali, D, and Roviello, G
- Abstract
PURPOSE: To identify hypoxia-related biomarkers indicative of response and resistance to epirubicin treatment in patients with locally advanced breast cancer. PATIENTS AND METHODS: One hundred seventy-six women with T2-4 N0-1 breast tumours 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 tumour proteins involved in cell survival, hypoxia, angiogenesis and growth factor, were assessed by immunohistochemistry in pre-treatment samples. A multivariate generalized linear regression approach was applied using a penalized least-square minimization to perform variable selection and regularization. RESULTS: VEGF and GLUT-1 expression were significantly positively associated with complete response (CR) to treatment in all leave-one-out iterations. Bcl-2 expression was inversely correlated with pCR, whilst EPO expression was positively correlated with pathological complete response (pCR). Haemaglobin and HIF-1a nuclear expression were inversely correlated with pCR. HB and HIF-1a expression were associated with a higher risk of relapse and overall survival. CONCLUSION: Hypoxic biomarkers determines the epirubicin resistance in breast cancer. Assessment of such biomarkers, may be useful for predicting chemosensitivity and also anthracycline-based treatment outcome.
- Published
- 2017