title: Immunohistochemical features associated with sensitivity to lapatinib-plus-capecitabine and resistance to trastuzumab in HER2-positive breast cancer.
abstract: OBJECTIVE
  To identify immunohistochemical (IHC) features associated with sensitivity to lapatinib-plus-capecitabine (LX) and resistance to trastuzumab in human epidermal growth factor receptor (HER)-2-positive metastatic breast cancer.
  
  
  METHODS
  Expression levels of estrogen receptor, progesterone receptor, epidermal growth factor receptor, HER2, HER3/phosphorylated HER3 (pHER3), phosphatase and tensin homolog, thymidylate synthase (TYMS), and thymidine phosphorylase by IHC were compared between patients treated with LX following trastuzumab failure.
  
  
  RESULTS
  In 35 patients, HER2 was the only biomarker associated with LX treatment outcomes. A high HER2 level was associated with significantly longer survival and a tendency towards longer time-to-progression and higher response rates. Acquisition of trastuzumab resistance was associated with higher pHER3 and TYMS expression. Elevated pHER3 was predictive of superior treatment outcomes.
  
  
  CONCLUSIONS
  Up-regulation of pHER3 and TYMS was associated with trastuzumab resistance. High HER2 and increased pHER3 IHC levels correlated with favourable LX treatment outcomes in patients with HER2-positive metastatic breast cancer.
authors: Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, South Korea Cancer Research Institute, Seoul National University, Jongno-gu, Seoul, South Korea.
authors: Yongjun
authors: Y
authors: Cha
authors: Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, South Korea Cancer Research Institute, Seoul National University, Jongno-gu, Seoul, South Korea.
authors: Sae-Won
authors: SW
authors: Han
authors: Department of Pathology, Seoul National University Hospital, Jongno-gu, Seoul, South Korea.
authors: Hyesil
authors: H
authors: Seol
authors: Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, South Korea Cancer Research Institute, Seoul National University, Jongno-gu, Seoul, South Korea.
authors: Do-Youn
authors: DY
authors: Oh
authors: Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, South Korea Cancer Research Institute, Seoul National University, Jongno-gu, Seoul, South Korea.
authors: Seock-Ah
authors: SA
authors: Im
authors: Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, South Korea Cancer Research Institute, Seoul National University, Jongno-gu, Seoul, South Korea Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Yeongtong-gu, Suwon-si, South Korea.
authors: Yung-Jue
authors: YJ
authors: Bang
authors: Department of Pathology, Seoul National University Hospital, Jongno-gu, Seoul, South Korea Cancer Research Institute, Seoul National University, Jongno-gu, Seoul, South Korea.
authors: In Ae
authors: IA
authors: Park
authors: Department of Surgery, Seoul National University Hospital, Jongno-gu, Seoul, South Korea Cancer Research Institute, Seoul National University, Jongno-gu, Seoul, South Korea.
authors: Wonshik
authors: W
authors: Han
authors: Department of Surgery, Seoul National University Hospital, Jongno-gu, Seoul, South Korea Cancer Research Institute, Seoul National University, Jongno-gu, Seoul, South Korea.
authors: Dong-Young
authors: DY
authors: Noh
authors: Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, South Korea Cancer Research Institute, Seoul National University, Jongno-gu, Seoul, South Korea Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Yeongtong-gu, Suwon-si, South Korea kimty@snu.ac.kr.
authors: Tae-You
authors: TY
authors: Kim
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007150:Immunohistochemistry; D000077341:Lapatinib; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Breast cancer; HER2; HER3; TYMS; capecitabine; lapatinib; trastuzumab