Overexpression of hypoxia-inducible factor HIF-1α predicts early relapse in breast cancer:: Retrospective study in a series of 745 patients

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a transcription factor that is involved in tumour growth and metastasis by regulating genes involved in response to hypoxia. HIF-1 alpha protein overexpression has been shown in a variety of human cancers, but only 2 studies have documented the prognostic relevance of HIF-1 alpha expression in breast cancer. The aim of our study was to determine accurately the impact of HIF-1 alpha expression on prognosis in a large series (n = 745) of unselected patients with invasive breast cancer in terms of overall survival, local recurrence and distant metastasis risk. HIF-1 alpha expression was investigated using immunohistochemical assays on frozen sections, and correlated with patients' outcome (median follow-up = 13.5 years). Univariate (Kaplan-Meier) analysis showed that high levels of HIF-1 alpha expression (cutoff = 10%) significantly correlated with poor overall survival (p = 0.019). HIF-1 alpha expression correlated with high metastasis risk among the whole group of patients (p = 0.008). Multivariate analysis (Cox model) showed that the HIF-1 alpha predictive value was independent of other current prognostic indicators. Moreover among node negative ones, HIF-1 alpha expression was also significantly predictive of metastasis risk (p = 0.03) and of relapse (p = 0.03). All the data suggest that HIF-1 alpha is associated with a worse prognosis in patients with invasive breast carcinoma. Furthermore HIF-1 alpha immunodetection may be considered as a potential indicator for selecting patients who could benefit from specific therapies interfering with HIF-1 alpha pathway. (c) 2005 Wiley-Liss, Inc.