title: Correlation of HER2, p95HER2 and HER3 expression and treatment outcome of lapatinib plus capecitabine in her2-positive metastatic breast cancer.
abstract: BACKGROUND
  Lapatinib plus capecitabine is an effective treatment option for trastuzumab-refractory HER2-positive metastatic breast cancer. We have investigated the correlation between quantitative measures of HER2, p95HER2, and HER3 and treatment outcomes using lapatinib and capecitabine.
  
  
  METHODS
  Total HER2 (H2T), p95HER2 (p95), and total HER3 (H3T) expression were quantified in formalin-fixed paraffin-embedded samples using the VeraTag assays. Patients received lapatinib and capecitabine treatment following trastuzumab failure according to the Lapatinib Expanded Access Program. The association between the protein expression levels and clinical outcomes was analyzed.
  
  
  RESULTS
  A total of 52 patients were evaluable. H2T level was significantly higher in responders (median 93.49 in partial response, 47.66 in stable disease, and 17.27 in progressive disease; p = 0.020). Longer time-to-progression (TTP) was observed in patients with high H2T [p = 0.018, median 5.2 months in high (>14.95) vs. 1.8 in low (<14.95)] and high H3T [p = 0.017, median 5.0 months in high (>0.605) vs. 2.2 in low (<0.605)]. Patients having both high H2T and high H3T had significantly longer TTP [adjusted hazard ratio (HR) 0.38 (95% CI 0.20-0.73), p = 0.004] and overall survival [adjusted HR 0.46 (95% CI 0.24-0.89), p = 0.020]. No significant association between p95 and response or survival was observed.
  
  
  CONCLUSIONS
  These data suggest a correlation between high HER2 and high HER3 expression and treatment outcome, while no significant difference was observed between clinical outcome and p95 expression level in this cohort of HER2-positive, trastuzumab-refractory metastatic breast cancer patients treated with lapatinib and capecitabine.
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Sae-Won
authors: SW
authors: Han
authors: Yongjun
authors: Y
authors: Cha
authors: Agnes
authors: A
authors: Paquet
authors: Weidong
authors: W
authors: Huang
authors: Jodi
authors: J
authors: Weidler
authors: Yolanda
authors: Y
authors: Lie
authors: Thomas
authors: T
authors: Sherwood
authors: Michael
authors: M
authors: Bates
authors: Mojgan
authors: M
authors: Haddad
authors: In Hae
authors: IH
authors: Park
authors: Do-Youn
authors: DY
authors: Oh
authors: Keun Seok
authors: KS
authors: Lee
authors: Seock-Ah
authors: SA
authors: Im
authors: Yung-Jue
authors: YJ
authors: Bang
authors: Jungsil
authors: J
authors: Ro
authors: Tae-You
authors: TY
authors: Kim
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D000069287:Capecitabine; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000096:biosynthesis* / Q000235:genetics; D015996:Survival Rate; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D000068878:Trastuzumab; C508053:ERBB2 protein, human