title: A phase II study on metastatic breast cancer patients treated with weekly vinorelbine with or without trastuzumab according to HER2 expression: changing the natural history of HER2-positive disease.
abstract: OBJECTIVE
  To observe whether in pretreated metastatic breast cancer patients with HER2-positive disease vinorelbine plus trastuzumab can produce different overall response rate (ORR), time to progression (TTP), and overall survival (OS) from women with HER2-negative tumors treated with vinorelbine alone.
  
  
  METHODS
  Between June 2000 and January 2004, 68 consecutive women were enrolled: 33 patients received vinorelbine (V) alone, while 35 patients were given trastuzumab plus vinorelbine (T+V) according to HER2 expression determined by immunohistochemistry. In tumors scored +2, HER2 gene amplification was determined by fluorescence in situ hybridization.
  
  
  RESULTS
  In patients treated with V (HER2-negative tumors) the ORR was 27.3%, while in those given T+V (HER2 positive tumors) the ORR was 51.4%. The median duration of response was 8 months for women treated with V and 10 months for those who received T+V. Patients given T+V had a longer TTP (9 months) and OS (27 months) than those receiving V alone (6 months and 22 months respectively). Toxicity was mild in both groups. Concerning cardiotoxicity in T+V group, 7 patients (20%) had left ventricular systolic disfunction.
  
  
  CONCLUSIONS
  Our data suggest that trastuzumab can change the natural history of HER2-positive metastatic breast cancer. In fact, when treated with trastuzumab, women with HER2-positive disease had better prognosis than patients with HER2-negative tumors. Conducting a formal phase III trial comparing vinorelbine alone vs vinorelbine plus trastuzumab in HER2-positive metastatic breast cancer women could be debatable.
authors.affiliation: Division of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Papaldo
authors.forename: A
authors.initials: A
authors.lastname: Fabi
authors.forename: G
authors.initials: G
authors.lastname: Ferretti
authors.forename: M
authors.initials: M
authors.lastname: Mottolese
authors.forename: A M
authors.initials: AM
authors.lastname: Cianciulli
authors.forename: B
authors.initials: B
authors.lastname: Di Cocco
authors.forename: M S
authors.initials: MS
authors.lastname: Pino
authors.forename: P
authors.initials: P
authors.lastname: Carlini
authors.forename: S
authors.initials: S
authors.lastname: Di Cosimo
authors.forename: I
authors.initials: I
authors.lastname: Sacchi
authors.forename: I
authors.initials: I
authors.lastname: Sperduti
authors.forename: C
authors.initials: C
authors.lastname: Nardoni
authors.forename: F
authors.initials: F
authors.lastname: Cognetti
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000068878:Trastuzumab; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014747:Vinblastine; D000068878:Trastuzumab; D000077235:Vinorelbine