Phosphorylated S6 Kinase-1 as Predictive Marker of Lapatinib Efficacy in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Patients.
- Author:
Eun Byeol KO
1
;
Min Ki SEONG
;
Hyang Suk CHOI
;
Chan Sub PARK
;
Ji Hye CHOI
;
Jin Kyung LEE
;
Hyesil SEOL
;
Hyun Ah KIM
;
Woo Chul NOH
Author Information
- Publication Type:Original Article
- Keywords: Breast neoplasms; Human epidermal growth factor receptor 2; Lapatinib; Ribosomal protein S6 kinases
- MeSH: Animals; Breast Neoplasms*; Breast*; Disease-Free Survival; Epidermal Growth Factor*; Humans*; Immunohistochemistry; Mice; Multivariate Analysis; Prognosis; Receptor, Epidermal Growth Factor*; Retrospective Studies; Ribosomal Protein S6; Ribosomal Protein S6 Kinases
- From: Journal of Breast Disease 2017;5(2):57-63
- CountryRepublic of Korea
- Language:English
- 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.
