J Cancer 2018; 9(17):2987-2993. doi:10.7150/jca.25679

Research Paper

Impact of menopausal status and HER-2/neu protein on efficacy of EGFR-TKI in EGFR mutant patients with non-small cell lung cancer

Zi-Jun Yin1,2, Hai-Yan Tu2, Ming Fu3, Wen-Zhao Zhong2, She-Juan An2, Hong-Hong Yan2, Hua-Jun Chen2, Hui-Ran Lin4, Yi-Long Wu2✉

1. Department of Oncology, The First Affiliated Hospital, Jinan University, Guangzhou, China
2. Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
3. The First Affiliated Hospital, Jinan University, Guangzhou, China
4. Laboratory Animal Management Office, Public Service Platform for Science and Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

Abstract

Clinical studies have confirmed epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) used in lung cancer patients with EGFR mutations can obtain a better result, but still part of the patients with poor efficacy. EGFR mutation is highly related to female, nonsmoking and adenocarcinoma. Thus, we hypothesize that estrogen and circulating HER-2/neu protein might influence the efficacy of EGFR-TKIs in EGFR mutant patients with non-small cell lung cancer. HER-2/neu expression level of 357 eligible patients in its peripheral serum was determined using ELISA. The median progression-free survival (PFS) in five groups (premenopausal group, perimenopause group, peri to postmenopausal group, postmenopausal group and control group) was statistically difference (P = 0.025). Premenopausal group could predict the efficacy of EGFR-TKI (HR = 2.45, 95% CI = 1.42-4.23, P = 0.001). No statistical significance was found in median overall survival (OS) among five groups. Optimal diagnostic cut off value of HER-2/neu was set at 47.5 ng/ml, with P = 0.0607. As the cutoff value to 47.5 ng/ml division, concentrations and menopausal status was of no significant difference (P = 0.874). PFS of the group below 47.5 ng/ml was significantly longer than that of the group over 47.5 ng/ml (P = 0.000). HER-2/neu concentration was positively correlated with optimal efficacy (P = 0.042). HER-2/neu concentration over than 47.5 ng/ml was a risk factor of EGFR-TKI prognosis. Premenopausal status is an independent predictor of EGFR-TKI curative effect and circulating HER-2/neu protein is an independent prognostic factor in patients with advanced NSCLC.

Keywords: menopausal status, HER-2/neu, human epidermal growth factor receptor-2, non-small-cell lung cancer, efficacy

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How to cite this article:
Yin ZJ, Tu HY, Fu M, Zhong WZ, An SJ, Yan HH, Chen HJ, Lin HR, Wu YL. Impact of menopausal status and HER-2/neu protein on efficacy of EGFR-TKI in EGFR mutant patients with non-small cell lung cancer. J Cancer 2018; 9(17):2987-2993. doi:10.7150/jca.25679. Available from http://www.jcancer.org/v09p2987.htm