title: [Efficacy and prognostic analysis of retreatment with trastuzumab-based therapy after multi-line targeted therapy resistance in HER2-positive metastatic breast cancer].
abstract: OBJECTIVE
  To evaluate the predictive factors for efficacy and prognosis of retreatment trastuzumab in the patients with HER2 positive metastatic breast cancer (MBC) developing successive resistance to multi-line targeting therapies.
  
  
  METHODS
  The data of 29 patients with HER2 positive MBC were collected from July 2008 to July 2010 at our department. All patients were treated with trastuzumab, lapatinib and retreated with trastuzumab sequentially. Twenty-one patients progressed during the initial trastuzumab therapy. All patients were treated with lapatinib to disease progression and retreated with trastuzumab to disease progression or death subsequently. A Log-rank test was used for univariate analysis and a Cox regression model was employed for multivariate analysis.
  
  
  RESULTS
  The efficacy showed no significant difference between the patients with progression or those without progression during the initial trastuzumab therapy. The time-to-progression (TTP) of prior lapatinib therapy was an influencing factor of median progression-free survival (PFS) (P < 0.0001) and the duration from discontinuation of lapatinib to trastuzumab retreatment an influencing factor of median overall survival (OS) (P = 0.008) of trastuzumab retreatment in our univariate analysis. The median PFS of trastuzumab retreatment for patients with TTP of lapatinib therapy > 12 weeks (hazard ratio (HR) = 0.02, P = 0.003) or whose duration of double trastuzumab treatment ≤ 1 year (HR = 0.26, P = 0.03) was significantly prolonged in multivariate analysis. Meanwhile, the death risk of patients whose duration from discontinuation of lapatinib to trastuzumab retreatment ≤ 4 weeks decreased 89% as compared with trastuzumab retreatment (HR = 0.11, P = 0.004).
  
  
  CONCLUSIONS
  TTP of prior lapatinib therapy and the duration of double trastuzumab treatment are two predictive factors of PFS of trastuzumab retreatment. And the duration from discontinuation of lapatinib to trastuzumab retreatment is an important independent prognostic factor for trastuzumab retreatment. The patients with HER2 positive MBC should be treated continually with anti-HER2 targeted therapy.
authors.affiliation: Department of Breast Cancer, Affiliated Hospital, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Bian
authors.forename: Ze-fei
authors.initials: ZF
authors.lastname: Jiang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Jin-jie
authors.initials: JJ
authors.lastname: Song
authors.forename: Yun-fei
authors.initials: YF
authors.lastname: Guo
authors.forename: Hui-qiang
authors.initials: HQ
authors.lastname: Zhang
authors.forename: Shao-hua
authors.initials: SH
authors.lastname: Zhang
authors.forename: Shi-kai
authors.initials: SK
authors.lastname: Wu
authors.forename: San-tai
authors.initials: ST
authors.lastname: Song
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D019233:Retreatment; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab