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Immunohistochemical features associated with sensitivity to lapatinib-plus-capecitabine and resistance to trastuzumab in HER2-positive breast cancer. | LitMetric
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
Published: August 2014
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Article 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.
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