In this issue of The Oncologist, Alvarez et al.[1] present a timely and comprehensive review of the data concerning bevacizumab in the treatment of patients with advanced breast cancer. The authors discuss the role of angiogenesis, including related therapeutic approaches as well as early clinical trials of bevacizumab, and appropriately focus on the randomized evidence. In summary, the three large first-line trials comparing chemotherapy alone with chemotherapy plus bevacizumabEastern Cooperative Oncology Group (ECOG) 2100, AVADO (Avastin and Docetaxel), and RIBBON-1 (Regimens in Bevacizumab for Breast Oncology)-met their primary endpoints and showed a statistically significant longer progression-free survival (PFS) duration. Pooled results demonstrated PFS intervals of 9.2 months and 6.7 months for patients treated with and without bevacizumab, respectively (hazard ratio, 0.64; 95% confidence interval [CI], 0.48 -0.69). The results were not homogenous, however, with median differences of 5.5 months in ECOG 2100 and 1.2-2.9 months in the other studies.The median, 1-year, and overall survival outcomes did not differ between the control and treatment arms in any of the individual trials or in the combined individual patient data metaanalysis [2]. Furthermore, there were no differences in any of the subgroups analyzed. The authors and the oncology community have raised potential hypotheses to explain this phenomenon, including the use of multiple further treatments upon progression, patients on placebo crossing over to receive bevacizumab, different interactions and potentials for synergism with each chemotherapy backbone, heterogeneous biology and sample populations, and the modest benefits of bevacizumab, among others [1,3,4]. The activity of bevacizumab described here must be balanced with its adverse event profile. A meta-analysis of five randomized trials [5] showed the following to be more common when bevacizumab was added to chemotherapy in the treatment of breast cancer (all differences were statistically significant): proteinuria (odds ratio [OR], 27.68), hypertension (OR, 12.76), left ventricular dysfunction (OR, 2.25), and hemorrhagic events (OR, 4.07). Although these adverse events have the potential to cause complications, most patients do not seem to have a negative impact on their quality of life (QOL) with the addition of bevacizumab, and in the same meta-analysis there were no statistically significant differences for gastrointestinal perforation, vascular events, fatal events, or febrile neutropenia. A larger meta-analysis of 16 randomized trials [6] with 10,217 patients, which included patients with other cancers, however, showed the addition of bevacizumab to be associated with a higher risk for fatal events (relative risk [RR], 1.33; 95% CI, 1.02-1.73; p ϭ .04; incidence, 2.9% versus 2.2% for bevacizumab versus chemotherapy alone). There was a higher risk for fatal events for individuals receiving taxanes or platinum agents (RR, 3.49; 95% CI, 1.82-6.66; incidence, 3.3% versus 1.0%) but not for...