The life, death, and attempted rebirth of bevacizumab in breast cancer

Abstract

Breast cancer is the leading cause of cancer in women. In recent years, there has been immense drug discovery and development in the field of breast cancer. Most recently, the role of vascular endothelial growth factor has moved to the treatment forefront with bevacizumab immersed into the literature as well as the media. Bevacizumab, a vascular endothelial growth factor inhibitor FDA approved for the treatment of other cancers, was first studied in metastatic breast cancer. Its use in human epidermal growth factor receptor 2-negative metastatic breast cancer ultimately failed to show an improvement in overall survival in landmark trials (E2100, AVADO, RIBBON-1 and RIBBON-2) despite its positive impact on progression-free survival. The role is yet to be determined in triple negative breast cancer as well as in the adjuvant and neoadjuvant settings. Trends begin to emerge as bevacizumab is combined with other chemotherapeutic drugs in terms of toxicities. The addition of bevacizumab is associated with an increase in the dose-limiting toxicities of the drugs combined in the regimen. As previous literature suggest, hypertension and proteinuria were also seen with the addition of bevacizumab, both of which are known adverse events. Lastly, there is a trend towards increased incidence of heart failure when bevacizumab is combined with another cardiotoxic medication, doxorubicin. This toxicity has been shown to be reversible in the majority of the cases and has a low incidence in the currently published literature.

Microvessel Density (MVD) in Locally Advanced Breast Cancer

“…The phase 3 trial from 10 countries, with bevacizumab with capecitabine and bevacizumab alone, concluded that the former benefits both progressionfree survival and overall survival in patients with Her2 negative tumours (Gligorov et al, 2014). However, other trials such as (E2100, AVADO, RIBBON-1 and RIBBON-2) showed that this therapy does not improve overall survival of patients with breast cancer (Seddon et al, 2014). Despite this, there may be a benefit with bevacizumab, when the initial MVD is higher since it enhanced vascular normalization.…”

The Role of the Neuropilins in Tumour Angiogenesis and Tumour Progression

“…On the other hand, bevacizumab can induce normalization of newly formed vessels, and thus allow enhanced delivery of chemotherapy to the tumours (Jain, 2005). Furthermore, Avastin has recently been removed as a breast cancer therapy due to adverse effects associated increased cardiovascular toxicity, although this decision is still controversial (Seddon et al, 2014). Thus there is an argument for additional anti-angiogenic therapies displaying reduced adverse effects to anti-VEGF therapy.…”