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Hypoxia, a common consequence of solid tumor growth in breast cancer and other cancers, serves to propagate a cascade of molecular pathways which include angiogenesis, glycolysis, and alterations in microenvironmental pH. Hypoxia-inducible factors, heterodimeric DNA binding complexes composed of two subunits, provide critical regulation of this response. This review presents a synopsis of the genes induced by hypoxia in the context of breast cancer and discusses how upregulation of HIF-1 activity, and the homologous factor HIF-2, are not only fundamental for the adaptation to hypoxia but also may be critical for tumor progression.

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Purpose: This phase 1/2 study was designed to test toxicity and effectiveness of combination chemotherapy and concurrent radiotherapy in the treatment of invasive bladder cancer. Methods and Materials: 17 patients with localised muscle-invasive bladder cancer, clinical stages T2–3 N0, M0, were treated with a radiotherapy schedule of 55 Gy in 20 fractions over 4 weeks restricted to the bladder and 3 cycles of concurrent dose-intensive combination chemotherapy consisting of cisplatin 60 mg/m², vincristine 2 mg and methotrexate 60 mg/m² at 10-day intervals (MOPq10). Results: The complete remission rate following MOPq10 chemotherapy and radiotherapy was 88% as assessed at first cystoscopy with 82% remaining disease-free at 1 year. Risk factor analysis shows those older than 63 years (median) and those with creatinine clearance equal or less than the mean did worse. Actuarial disease-free survival at 2 years was 68% and of the patients treated 4/17 experienced acute G3/4 toxicity. Conclusion: This combination regimen was feasible. Its high initial response rate justifies further exploration in a randomised phase 2/3 trial setting with bladder volume and quality of life assessment.