title: Effect of adjuvant/neoadjuvant trastuzumab on clinical outcomes in patients with HER2-positive metastatic breast cancer.
abstract: BACKGROUND
  The purpose of the current study was to describe the outcomes of patients with human epidermal growth factor receptor 2 (HER2)-overexpressed/amplified (HER2+) early breast cancer who received adjuvant or neoadjuvant trastuzumab-based therapy and were subsequently retreated with trastuzumab for metastatic disease.
  
  
  METHODS
  A total of 353 patients with metastatic HER2+ breast cancer who were treated with trastuzumab as part of their first-line treatment for metastatic disease were identified. A total of 75 patients had received adjuvant or neoadjuvant trastuzumab-based therapy for early breast cancer, and 278 had not. Clinical outcomes of patients who had or had not received prior trastuzumab were compared using Cox proportional hazards regression and logistic regression analyses. Survival was estimated using the Kaplan-Meier method.
  
  
  RESULTS
  The clinical benefit (complete response, partial response, or stable disease of ≥ 6 months) rates were 71% in the group who did not receive prior trastuzumab and 39% in the group previously treated with trastuzumab. The adjusted odds ratios were 0.28 (95% confidence interval [95% CI], 0.13-0.59; P = .0009) for clinical benefit rates and 0.39 (95% CI, 0.18-0.82; P = .038) for objective (complete or partial) response rates. In the univariate analysis, the median overall survival rate was longer in the group who did not receive prior trastuzumab (36 months vs 28 months) (hazards ratio, 1.47; 95% CI, 1.07-2.01 [P = .022]). The multivariate analysis found no significant difference in overall survival.
  
  
  CONCLUSIONS
  When treated with trastuzumab for metastatic disease, patients with HER2+ breast cancer without prior exposure to trastuzumab were found to have superior clinical outcomes to those with prior exposure. Prior trastuzumab exposure should be considered in treatment algorithms and in HER2-targeted clinical trial enrollment for metastatic disease.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rashmi K
authors.initials: RK
authors.lastname: Murthy
authors.forename: Ankur
authors.initials: A
authors.lastname: Varma
authors.forename: Priyankana
authors.initials: P
authors.lastname: Mishra
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.forename: Elliana
authors.initials: E
authors.lastname: Young
authors.forename: James L
authors.initials: JL
authors.lastname: Murray
authors.forename: Kimberly H
authors.initials: KH
authors.lastname: Koenig
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Moulder
authors.forename: Amal
authors.initials: A
authors.lastname: Melhem-Bertrandt
authors.forename: Sharon H
authors.initials: SH
authors.lastname: Giordano
authors.forename: Daniel
authors.initials: D
authors.lastname: Booser
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012189:Retrospective Studies; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: breast neoplasms; drug resistance; human epidermal growth factor receptor 2 (HER2); metastasis; outcomes; trastuzumab