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Anticancer Res. 2014;34(8):4275-80.

Immunohistochemical features associated with sensitivity to lapatinib-plus-capecitabine and resistance to trastuzumab in HER2-positive breast cancer.

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제1저자 차용준 · 교신저자 김태유

PMID 25075058 IF 1.8 혈액종양내과
소속 (6)
  1. Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, South Korea Cancer Research Institute, Seoul National University, Jongno-gu, Seoul, South Korea.
  2. Department of Pathology, Seoul National University Hospital, Jongno-gu, Seoul, South Korea.
  3. 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.
  4. Department of Pathology, Seoul National University Hospital, Jongno-gu, Seoul, South Korea Cancer Research Institute, Seoul National University, Jongno-gu, Seoul, South Korea.
  5. Department of Surgery, Seoul National University Hospital, Jongno-gu, Seoul, South Korea Cancer Research Institute, Seoul National University, Jongno-gu, Seoul, South Korea.
  6. 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.

Abstract

AIM 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.

PATIENTS AND 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.

CONCLUSION 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.

Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Keywords

Breast cancerHER2HER3TYMScapecitabinelapatinibtrastuzumab

그 밖의 정보
출판 형태
Journal Article
저널
Anticancer research · eISSN 1791-7530
MeSH
Adult · Aged · Antibodies, Monoclonal, Humanized / therapeutic use · Antineoplastic Combined Chemotherapy Protocols / therapeutic use · Breast Neoplasms / chemistry / drug therapy / mortality · Capecitabine · Deoxycytidine / administration & dosage / analogs & derivatives · Drug Resistance, Neoplasm · Female · Fluorouracil / administration & dosage / analogs & derivatives · Humans · Immunohistochemistry · Lapatinib · Middle Aged · Quinazolines / administration & dosage · Erb-b2 Receptor Tyrosine Kinases / analysis · Trastuzumab
Substances
Antibodies, Monoclonal, Humanized · Capecitabine · Deoxycytidine · Fluorouracil · Lapatinib · Quinazolines · Erb-b2 Receptor Tyrosine Kinases · Trastuzumab · ERBB2 protein, human