title: Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer.
abstract: BACKGROUND
  In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression). Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy.
  
  
  METHODS
  Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP) on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS) were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression) were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. p values < 0.05 were considered to indicate statistical significance.
  
  
  RESULTS
  Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26), and 8 months (95% CI 6.25-9.74) on first-line, respectively (n.s.). In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter.
  
  
  CONCLUSIONS
  Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.
authors.affiliation: Department of Medicine 1 and Cancer Centre, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria. rupert.bartsch@meduniwien.ac.at
authors.forename: Rupert
authors.initials: R
authors.lastname: Bartsch
authors.forename: Catharina
authors.initials: C
authors.lastname: De Vries
authors.forename: Ursula
authors.initials: U
authors.lastname: Pluschnig
authors.forename: Peter
authors.initials: P
authors.lastname: Dubsky
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Bago-Horvath
authors.forename: Simon P
authors.initials: SP
authors.lastname: Gampenrieder
authors.forename: Margaretha
authors.initials: M
authors.lastname: Rudas
authors.forename: Robert M
authors.initials: RM
authors.lastname: Mader
authors.forename: Andrea
authors.initials: A
authors.lastname: Rottenfusser
authors.forename: Christoph
authors.initials: C
authors.lastname: Wiltschke
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
authors.forename: Guenther G
authors.initials: GG
authors.lastname: Steger
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human