Yongjun Cha1, Sae-Won Han1, Hyesil Seol2, Do-Youn Oh1, Seock-Ah Im1, Yung-Jue Bang3, In Ae Park4, Wonshik Han5, Dong-Young Noh5, Tae-You Kim6. 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
AIM: To identify immunohistochemical (IHC) features associated with sensitivity to lapatinib-plus-capecitabine (LX) and resistance to trastuzumab in humanepidermal 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