Purpose: Hypoxia-inducible factor (HIF)-1α is a transcription factor that supports the adaptation of human cancer cells to hypoxia and is involved in various pathways supporting tumor growth and progression. The aim of this study was to determine the prognostic influence of HIF-1α expression in patients with advanced-stage breast cancer, evident by positive lymph nodes.

Experimental Design: Expression of HIF-1α was determined immunohistochemically in 206 patients with lymph node-positive breast cancer. Furthermore, the interrelationship of HIF-1α with p53 and HER-2 protein expression, estrogen receptor density, and survival was analyzed. Colocalization of p53 and HIF-1α proteins was analyzed by confocal laser scanning microscopy.

Results: Strong nuclear expression of HIF-1α by invasive cancer cells was found in 48 patients (23.3%), moderate expression was found in 74 patients (35.9%), and weak expression was found in 35 patients (17%); no expression was observed in 49 patients (23.8%). HIF-1α protein overexpression was associated with significantly shorter overall and disease-free survival time (P = 0.003 and P = 0.001, respectively; Cox regression analysis). No correlation of HIF-1α and HER-2 expression or estrogen receptor density was observed.

Conclusions: This study shows that HIF-1α is an independent prognostic factor for an unfavorable prognosis in patients with lymph node-positive breast cancer. Our results indicate that patients with advanced-stage breast cancers might profit from future therapies targeting HIF-1α.