%0 Journal Article
%T Hypoxia and oxidative stress in breast cancer: Tumour hypoxia ¨C therapeutic considerations
%A Kaye J Williams
%A Rachel L Cowen
%A Ian J Stratford
%J Breast Cancer Research
%D 2001
%I BioMed Central
%R 10.1186/bcr316
%X Tissue hypoxia, owing to an inadequate blood supply, is a common feature of most solid tumours, and breast carcinoma is no exception. The accessibility of breast carcinomas has enabled the use of polarographic O2 needle electrodes to assess tumour oxygenation. Such studies have demonstrated an overall lower median pO2 level in malignant tumours compared with benign tumours and normal breast tissue. Electrode measurements obtained without the use of general anaesthesia have revealed median pO2 values of 23¨C28 mmHg for tumours, compared with 42 mmHg for benign lesions and 54¨C65 mmHg for normal tissue [1,2]. Of all readings taken from breast cancers, 30¨C40% fall below 10 mmHg, which is very rarely seen in normal tissue [1,2]. The study of Vaupel et al also revealed that nearly 40% of breast malignancies exhibit tumour regions with oxygen concentrations below that required for half-maximal radiosensitivity (pO2 < 2.5 mmHg) [1].Radiotherapy and chemotherapy are both commonly incorporated into breast cancer treatment regimens. Retrospective studies in other malignancies have determined that poor tumour oxygenation is the strongest prognostic indicator of radiotherapy treatment outcome [3,4,5]. In keeping with these findings, measurements of breast tumour pO2 distribution, prior to radiotherapy, have indicated that oxygen tension is an important modifier of radiation treatment outcome and is sufficient to predict local response [6]. In addition, the success of hypothermia as an adjuvant to radiation therapy for breast cancer treatment may be compromised in tumours with histopathology suggestive of a high level of chronic hypoxia [7]. The effects of hypoxia on the success of chemotherapy have not been clearly established. There is, however, direct evidence that hypoxic cells within tumour xenografts are refractile to chemotherapeutic agents and the quiescent nature of hypoxic cells may render them insensitive to agents that specifically target rapidly dividing cells [8,9].
%K bioreductive drugs
%K hypoxia
%K hypoxia responsive element
%K reductase enzymes
%U http://breast-cancer-research.com/content/3/5/328