Blood supply, oxygenation status and metabolic micromilieu of breast cancers: characterization and therapeutic relevance.

The metabolic microenvironment of a tumor is predominantly determined by the efficacy of blood flow, flux parameters (such as diffusion and convective currents in the interstitial space) and metabolic rates. The most important factors in this context include oxygen and nutrient supply, tissue pH and the bioenergetic status. It is now widely accepted that the metabolic microenvironment of a tumor can dramatically influence a range of factors such as proliferation rate, cell cycle position, growth rate and the development of apoptosis and necrosis. At the same time, these parameters can have an impact on tumor detection, therapeutic response to conventional irradiation, some chemotherapy agents and other non-surgical treatment modalities, while also having the capacity to modulate malignant progression (e.g., enhanced local spread, metastasis). The metabolic microenvironment appears to have a potentially important role to play in the prediction of long-term treatment outcome, and thus might be useful as a prognostic factor. Currently available information related to the parameters defining the metabolic microenvironment in breast cancers are presented in this review. According to these data, significant variations in these relevant factors are likely to occur between different locations within a tumor, and between tumors of the same clinical size, stage, grade and histology. The <physiological barriers> to treatment are also considered.