Tumour oxygenation: implications for breast cancer prognosis.

There are areas of limited oxygen availability in most solid tumours, including breast cancer. Hypoxia in solid tumours is mainly a consequence of poor perfusion. Structural and functional abnormalities of newly formed tumour vessels cause spatial and temporal heterogeneity of tissue perfusion. The two principal mediators of hypoxia response, HIF-1 and HIF-2, are known to be stabilized at different oxygen levels and to have different temporal responses to hypoxia. Recently, stromal HIF-1 and HIF-2 have been suggested to have opposing roles in breast cancer progression. There is an established link between intralesional, severe hypoxia near areas of necrosis with high levels of HIF-1 and poor prognosis in breast cancer. However, the biological effects of moderate hypoxia and the hypoxic response of stromal cells are currently topics of intense investigation.