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Angiogenesis and tumor microenvironment: bevacizumab in the breast cancer model

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Abstract

Solid tumors require blood vessels for growth, and many new cancer therapies are directed against the tumor vasculature. Antiangiogenic therapies should destroy the tumor vasculature, thereby depriving the tumor of oxygen and nutrients. According to Jain et al., an alternative hypothesis could be that certain antiangiogenic agents can also transiently “normalize” the abnormal structure and function of tumor vasculature to make it more efficient for oxygen and drug delivery. With emphasize on the research works of Jain et al., the aim of this review is to describe the impact of antivascular endothelial growth factor (VEGF) therapy on “pseudo-normalization” of tumor vasculature and tumor microenvironment, its role in early and metastatic breast cancer, and the clinical evidence supporting this original concept. The phase III clinical trials showed that extended tumors, metastatic or locally advanced, are likely to benefit from bevacizumab therapy in combination with chemotherapy, assuming that a high level of tumor neoangiogenesis as in triple-negative tumors is the best target. In adjuvant setting, the lower level of tumor vasculature could mask a potential benefit of anti-VEGF therapy. All these findings highlight the need to identify biomarkers to help in the selection of patients most likely to respond to anti-VEGF therapy, to better understand the mechanism of angiogenesis and of resistance to anti-VEGF therapy according to molecular subtypes.

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Acknowledgments

The authors thank Isabelle Chapelle-Marcillac for her assistance in the medical writing.

Conflict of interest

All the authors received personal fees for the article from Laboratoires Roche France. Laboratoires Roche France supports the medical writing. Olivier Trédan received consulting fees from Roche, France.

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Authors and Affiliations

  1. Department of Medical Oncology, Centre Léon Bérard, 28 rue Laennec, 69373, Lyon Cedex, France

    Olivier Trédan

  2. Department of Pathology, Institut Claudius Régaud, Toulouse, France

    Magali Lacroix-Triki

  3. Department of Medical Oncology, Centre Georges-François Leclerc, Dijon, France

    Séverine Guiu

  4. Department of Medical Oncology, Centre Jean Perrin, Clermont-Ferrand, France

    Marie-Ange Mouret-Reynier

  5. Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France

    Jérôme Barrière

  6. Department of Medical Oncology, Institut Curie, Paris, France

    François-Clément Bidard

  7. Department of Radiotherapy, Centre Val d’Aurelle, Montpellier, France

    Antoine-Laurent Braccini

  8. Department of Medical Oncology, Hôpital Cochin, Paris, France

    Olivier Mir

  9. Department of Medical Oncology, Hôpital Jean Minjoz, Besançon, France

    Christian Villanueva

  10. Department of Hematology and Oncology, Hôpital de Hautepierre, Strasbourg, France

    Philippe Barthélémy

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  1. Olivier Trédan
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Trédan, O., Lacroix-Triki, M., Guiu, S. et al. Angiogenesis and tumor microenvironment: bevacizumab in the breast cancer model. Targ Oncol 10, 189–198 (2015). https://doi.org/10.1007/s11523-014-0334-9

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