title: Targeting angiogenesis in metastatic breast cancer.
abstract: Angiogenesis has become an important target in the treatment of several solid tumors, including breast cancer. As monotherapy, antiangiogenic agents have demonstrated limited activity in metastatic breast cancer (MBC); therefore, they have generally been developed for use in combination with chemotherapies. Thus far, the experience with antiangiogenic agents for MBC has been mixed. The results from one study assessing addition of the monoclonal antibody bevacizumab to paclitaxel led to approval of bevacizumab for MBC. However, the modest improvement of progression-free survival rates in subsequent MBC studies has led to reappraisal of bevacizumab. Phase III studies have not produced evidence supporting use of the multikinase inhibitor sunitinib alone or in combination with MBC chemotherapy. Experience with sorafenib in a phase IIb program indicates potential when used in select combinations, particularly with capecitabine; however, phase III confirmatory data are needed. Although antiangiogenic therapies combined with chemotherapy have increased progression-free survival rates for patients with MBC, increases in overall survival times have not been observed. Some studies have tried to combine antiangiogenic agents such as bevacizumab and sunitinib or sorafenib, but that approach has been limited because of toxicity concerns. Sequential use of antiangiogenic agents with differing mechanisms of action may be an effective approach. Despite setbacks, angiogenesis will likely remain an important target of treatment for selected patients with MBC.
authors: Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors: Sangeetha
authors: S
authors: Reddy
authors: Michael
authors: M
authors: Raffin
authors: Virginia
authors: V
authors: Kaklamani
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology; D000069287:Capecitabine; D017326:Clinical Trials, Phase III as Topic; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D017239:Paclitaxel / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077157:Sorafenib; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D009536:Niacinamide; D000068258:Bevacizumab; D000069287:Capecitabine; D000068338:Everolimus; D000077157:Sorafenib; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D017239:Paclitaxel; D005472:Fluorouracil; D000077210:Sunitinib; D020123:Sirolimus