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

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.

• Authors: Yongjun Cha, Sae-Won Han, Hyesil Seol, Do-Youn Oh, Seock-Ah Im, Yung-Jue Bang, In Ae Park, Wonshik Han, Dong-Young Noh, Tae-You Kim
• Journal: Anticancer research (Anticancer Res) Vol. 34 Issue 8 Pg. 4275-80 (Aug 2014) ISSN: 1791-7530 [Electronic] Greece
• PMID: 25075058 (Publication Type: Journal Article)
• Copyright: Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Quinazolines
• Lapatinib
• Deoxycytidine
• Capecitabine
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab
• Fluorouracil

Topics

• 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)
• Receptor, ErbB-2 (analysis)
• Trastuzumab