Phosphorylated S6 Kinase-1 as Predictive Marker of Lapatinib Efficacy in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Patients
Journal of Breast Disease 2017³â 5±Ç 2È£ p.57 ~ p.63
°íÀºº°(Ko Eun-Byeol) - Korea Institute of Radiological & Medical Sciences Korea Cancer Center Hospital Department of Surgery
¼º¹Î±â(Seong Min-Ki) - Korea Institute of Radiological & Medical Sciences Korea Cancer Center Hospital Department of Surgery
ÃÖÇâ¼÷(Choi Hyang-Suk) - Korea Institute of Radiological & Medical Sciences Korea Cancer Center Hospital Department of Surgery
¹ÚÂù¼·(Park Chan-Sub) - Korea Institute of Radiological & Medical Sciences Korea Cancer Center Hospital Department of Surgery
ÃÖÁöÇý(Choi Ji-Hye) - Korea Institute of Radiological & Medical Sciences Korea Cancer Center Hospital Department of Surgery
ÀÌÁø°æ(Lee Jin-Kyung) - Korea Institute of Radiological & Medical Sciences Korea Cancer Center Hospital Department of Laboratory Medicine
¼³Çý½Ç(Seol Hye-Sil) - Korea Institute of Radiological & Medical Sciences Korea Cancer Center Hospital Department of Pathology
±èÇö¾Æ(Kim Hyun-Ah) - Korea Institute of Radiological & Medical Sciences Korea Cancer Center Hospital Department of Surgery
³ë¿ìö(Noh Woo-Chul) - Korea Institute of Radiological & Medical Sciences Korea Cancer Center Hospital Department of Surgery
Abstract
Purpose: The 40S ribosomal protein S6 kinase-1 (S6K1) is a crucial downstream effector of the PI3K/AKT/mTOR pathway. S6K1 overexpression is found in 10% to 30% of breast cancers and is associated with aggressive disease and poor prognosis. Herein, we investigated the relationship between the expression of phosphorylated S6K1 (p-S6K1) and efficacy of lapatinib in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.
Methods: We retrospectively analyzed the data of 36 patients with HER2-positive metastatic breast cancer treated with lapatinib between January 2010 and September 2014. The p-S6K1 expression status of the primary tumor was assessed via immunohistochemistry using a mouse monoclonal antibody.
Results: Fourteen of the 36 patients (38.9%) had p-S6K1-positive tumors. The median progression-free survival (PFS) of patients with p-S6K1-positive tumors was significantly longer than that of patients with p-S6K1-negative tumors (13.4 months vs. 7.1 months, p=0.025). In multivariate analysis, p-S6K1 positivity remained an independent, favorable predictive factor for PFS (hazard ratio, 0.32; 95% confidence interval, 0.11?0.97; p=0.044).
Conclusion: The high expression of p-S6K1 was significantly associated with prolonged PFS, suggesting that p-S6K1 can be a potential biomarker for predicting the efficacy of lapatinib in patients with HER2-positive metastatic breast cancer.
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Breast neoplasms, Human epidermal growth factor receptor 2, Lapatinib, Ribosomal protein S6 kinases
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This study identified p-S6K1 as a potential valuable marker to predict successful outcome of lapatinib treatment.