The role of angiogenesis inhibition in the treatment of breast cancer.
In recent years, antiangiogenic therapy with the monoclonal antibody bevacizumab has demonstrated significant activity in patients with metastatic breast cancer. Bevacizumab is targeted against vascular endothelial growth factor (VEGF), a primary mediator of angiogenesis. Research is ongoing to define the mechanism of action of anti-VEGF treatment in order to predict who will respond to treatment and to monitor responses to treatment at the molecular level. The initial randomized phase III trial of bevacizumab evaluated capecitabine with bevacizumab versus capecitabine alone in patients with heavily pretreated metastatic breast cancer. The addition of bevacizumab to capecitabine did not improve progression-free survival in these patients. However, in the subsequent Eastern Cooperative Oncology Group 2100 trial of patients with previously untreated metastatic breast cancer, bevacizumab combined with paclitaxel doubled progression-free survival compared to paclitaxel alone. Based on these encouraging findings, current studies are evaluating bevacizumab in the adjuvant setting. The oral tyrosine kinase inhibitor sunitinib has shown activity in metastatic breast cancer, and additional agents are being investigated. Combination therapy consisting of antiangiogenic agents with chemotherapy, hormone therapy, or other agents is also being evaluated in hopes of improving treatment options for these patients.
Sledge
George W
GW
Indiana University Cancer Center, Indianapolis, Ind, USA.
Rugo
Hope S
HS
Burstein
Harold J
HJ
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000069287:Capecitabine; D017326:Clinical Trials, Phase III as Topic; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D015337:Multicenter Studies as Topic; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000077210:Sunitinib; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D017239:Paclitaxel; D005472:Fluorouracil; D000077210:Sunitinib