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

Hypoxia‐inducible factor‐1α (HIF‐1α) is a transcription factor that is involved in tumour growth and metastasis by regulating genes involved in response to hypoxia. HIF‐1α protein overexpression has been shown in a variety of human cancers, but only 2 studies have documented the prognostic relevance of HIF‐1α expression in breast cancer. The aim of our study was to determine accurately the impact of HIF‐1α 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‐1α 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‐1α expression (cutoff = 10%) significantly correlated with poor overall survival (p = 0.019). HIF‐1α expression correlated with high metastasis risk among the whole group of patients (p = 0.008). Multivariate analysis (Cox model) showed that the HIF‐1α predictive value was independent of other current prognostic indicators. Moreover among node negative ones, HIF‐1α expression was also significantly predictive of metastasis risk (p = 0.03) and of relapse (p = 0.035). All the data suggest that HIF‐1α is associated with a worse prognosis in patients with invasive breast carcinoma. Furthermore HIF‐1α immunodetection may be considered as a potential indicator for selecting patients who could benefit from specific therapies interfering with HIF‐1α pathway. © 2005 Wiley‐Liss, Inc.