J Breast Dis.  2017 Dec;5(2):57-63. 10.14449/jbd.2017.5.2.57.

Phosphorylated S6 Kinase-1 as Predictive Marker of Lapatinib Efficacy in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Patients

• Ko EB
• Seong MK
• Choi HS
• Park CS
• Choi JH
• Lee JK
• Seol H
• Kim HA
• Noh WC

• KMID: 2401816
• DOI: http://doi.org/10.14449/jbd.2017.5.2.57

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.

Keyword

Breast neoplasms; Human epidermal growth factor receptor 2; Lapatinib; Ribosomal protein S6 kinases

MeSH Terms

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
Epidermal Growth Factor
Receptor, Epidermal Growth Factor
Ribosomal Protein S6
Ribosomal Protein S6 Kinases