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.

Milani, M., Venturini, S., Bonardi, S., Allevi, G., Strina, C., Cappelletti, M. R., Corona, S. P., Aguggini, S., Bottini, A., Berruti, A., Jubb, A., Campo, L., Harris, A. L., Gatter, K., Fox, S. B., Generali, D., Roviello, G., Hypoxia-related biological markers as predictors of epirubicin- based treatment responsiveness and resistance in locally advanced breast cancer, <<ONCOTARGET>>, 2017; 8 (45): 78870-78881. [doi:10.18632/oncotarget.20239] [http://hdl.handle.net/10807/206446]

Hypoxia-related biological markers as predictors of epirubicin- based treatment responsiveness and resistance in locally advanced breast cancer

Venturini, Sergio
Formal Analysis
;
Generali, Daniele
Conceptualization
;
2017

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.
2017
Inglese
Milani, M., Venturini, S., Bonardi, S., Allevi, G., Strina, C., Cappelletti, M. R., Corona, S. P., Aguggini, S., Bottini, A., Berruti, A., Jubb, A., Campo, L., Harris, A. L., Gatter, K., Fox, S. B., Generali, D., Roviello, G., Hypoxia-related biological markers as predictors of epirubicin- based treatment responsiveness and resistance in locally advanced breast cancer, <<ONCOTARGET>>, 2017; 8 (45): 78870-78881. [doi:10.18632/oncotarget.20239] [http://hdl.handle.net/10807/206446]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/206446
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 7
social impact