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

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Milani, M; Venturini, S; Bonardi, S; Allevi, G; Strina, C; Cappelletti, MR; Corona, SP; Aguggini, S; Bottini, A; Berruti, A; ...Date
2017-10-03Source Title
OncotargetPublisher
IMPACT JOURNALS LLCUniversity of Melbourne Author/s
Fox, StephenAffiliation
Sir Peter MacCallum Department of OncologyMetadata
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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. (2017). Hypoxia-related biological markers as predictors of epirubicin-based treatment responsiveness and resistance in locally advanced breast cancer. ONCOTARGET, 8 (45), pp.78870-78881. https://doi.org/10.18632/oncotarget.20239.Access Status
Open AccessAbstract
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.
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