title: Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer.
abstract: BACKGROUND
  Bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, has shown clinical efficacy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. We evaluated the efficacy, measured according to the rate of pathological complete response (absence of invasive and intraductal disease in the breast and the axillary lymph nodes), and the safety of adding bevacizumab to neoadjuvant chemotherapy in patients with early-stage breast cancer.
  
  
  METHODS
  We randomly assigned 1948 patients with a median tumor size of 40 mm on palpation to receive neoadjuvant epirubicin and cyclophosphamide followed by docetaxel, with or without concomitant bevacizumab. Patients with untreated HER2-negative breast cancer were eligible if they had large tumors, hormone-receptor-negative disease, or hormone-receptor-positive disease with palpable nodes or positive findings on sentinel-node biopsy, and no increased cardiovascular or bleeding risk.
  
  
  RESULTS
  Overall, the rates of pathological complete response were 14.9% with epirubicin and cyclophosphamide followed by docetaxel and 18.4% with epirubicin and cyclophosphamide followed by docetaxel plus bevacizumab (odds ratio with addition of bevacizumab, 1.29; 95% confidence interval, 1.02 to 1.65; P=0.04); the corresponding rates of pathological complete response were 27.9% and 39.3% among 663 patients with triple-negative tumors (P=0.003) and 7.8% and 7.7% among 1262 patients with hormone-receptor-positive tumors (P=1.00). Breast-conserving surgery was possible in 66.6% of the patients in both groups. The addition of bevacizumab, as compared with neoadjuvant therapy alone, was associated with a higher incidence of grade 3 or 4 toxic effects (febrile neutropenia, mucositis, the hand-foot syndrome, infection, and hypertension) but with a similar incidence of surgical complications.
  
  
  CONCLUSIONS
  The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer. Efficacy was restricted primarily to patients with triple-negative tumors, in whom the pathological complete response is considered to be a reliable predictor of long-term outcome. (Funded by Sanofi-Aventis and Roche, Germany; ClinicalTrials.gov number, NCT00567554.).
authors.affiliation: Headquarters, German Breast Group, Neu-Isenburg, Germany. gunter.vonminckwitz@germanbreastgroup.de
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Holger
authors.initials: H
authors.lastname: Eidtmann
authors.forename: Mahdi
authors.initials: M
authors.lastname: Rezai
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Hans
authors.initials: H
authors.lastname: Tesch
authors.forename: Holm
authors.initials: H
authors.lastname: Eggemann
authors.forename: Iris
authors.initials: I
authors.lastname: Schrader
authors.forename: Kornelia
authors.initials: K
authors.lastname: Kittel
authors.forename: Claus
authors.initials: C
authors.lastname: Hanusch
authors.forename: Rolf
authors.initials: R
authors.lastname: Kreienberg
authors.forename: Christine
authors.initials: C
authors.lastname: Solbach
authors.forename: Bernd
authors.initials: B
authors.lastname: Gerber
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Georg
authors.initials: G
authors.lastname: Kunz
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Blohmer
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Maik
authors.initials: M
authors.lastname: Hauschild
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Berit Maria
authors.initials: BM
authors.lastname: Müller
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.forename: Valentina
authors.initials: V
authors.lastname: Nekljudova
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016015:Logistic Models; D015412:Mastectomy, Segmental; D055118:Medication Adherence; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003520:Cyclophosphamide; D015251:Epirubicin; D018719:Erb-b2 Receptor Tyrosine Kinases