title: Capecitabine after anthracycline and taxane exposure in HER2-negative metastatic breast cancer patients: response, survival and prognostic factors.
abstract: BACKGROUND
  Capecitabine is a widely accepted option in pre-treated metastatic breast cancer (MBC) patients. However, little is known about specific activity in molecularly defined subgroups of patients. Here, response, survival and prognostic factors were examined in a prospectively characterized cohort of human epidermal growth factor receptor 2 (HER2) negative MBC patients receiving capecitabine following anthracycline and taxane failure.
  
  
  METHODS
  Medical records from 75 HER2-negative MBC pre-treated with anthracycline and/or taxane and receiving capecitabine monotherapy at the Institut Paoli-Calmettes between 2002 and 2009 were reviewed. Univariate and multivariate analysis according the Cox regression model were employed to identify factors predictive for response, progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Overall, the objective response rate (ORR) was 29.3% (95% CI: 20-40). The ORR in HER2-negative/hormonal receptor (HRe) positive and HER2-negative/HRe-negative patients were 37% (95% CI: 26-50) and 0% (95% CI: 0-19), respectively, (p=0.003, Fisher's test). With a median follow-up of 35.2 months after capecitabine initiation, median PFS was 6.6 months (95% CI: 4.7-10.4) and median OS was 18.4 months (95% CI:14.1-24.9). In univariate analysis, HRe-negative status was the strongest prognostic factor for PFS (hazard ratio (HR)=2.09; p-value=0.015, log-rank test). In multivariate analysis, only three variables (HRe-negative status, initial disease-free interval <24 months and extra-regional lymph node involvement) were considered independently associated with poor PFS, while five variables (grade 2/3, initial disease-free interval <24 months, central nervous system metastases, interval between diagnosis of metastases and capecitabine initiation <24 months, and number of metastatic sites on capecitabine initiation) were associated with poor OS.
  
  
  CONCLUSIONS
  The median OS of pretreated patients with HER2-negative MBC receiving capecitabine is approximately 18 months, but HER2-negative/HRe-negative patients have a low probablility of response/disease control to capecitabine and require innovative therapies.
authors.affiliation: Oncologie Médicale, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, INSERM U891, 232, boulevard Sainte Marguerite, 13009 Marseille, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Gilabert
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.forename: Benjamin
authors.initials: B
authors.lastname: Esterni
authors.forename: Anne
authors.initials: A
authors.lastname: Madroszyk
authors.forename: Carole
authors.initials: C
authors.lastname: Tarpin
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Extra
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.forename: Anthony
authors.initials: A
authors.lastname: Gonçalves
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C080625:taxane