Tamoxifen therapy benefit predictive signature coupled with prognostic signature of post-operative recurrent risk for early stage ER+ breast cancer
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Hao Cai1, Xiangyu Li1, Jing Li1, Lu Ao1, Haidan Yan1, Mengsha Tong1, Qingzhou Guan1, Mengyao Li1, Zheng Guo1,2
1Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
2College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
Zheng Guo, e-mail: [email protected]
Keywords: breast cancer, relative expression ordering, prognostic signature, predictive signature, tamoxifen
Received: July 08, 2015 Accepted: October 23, 2015 Published: October 30, 2015
Two types of prognostic signatures for predicting recurrent risk of ER+ breast cancer patients have been developed: one type for patients accepting surgery only and another type for patients receiving post-operative tamoxifen therapy. However, the first type of signature cannot distinguish high-risk patients who cannot benefit from tamoxifen therapy, while the second type of signature cannot identify patients who will be at low risk of recurrence even if they accept surgery only. In this study, we proposed to develop two coupled signatures to solve these problems based on within-sample relative expression orderings (REOs) of gene pairs. Firstly, we identified a prognostic signature of post-operative recurrent risk using 544 samples of ER+ breast cancer patients accepting surgery only. Then, applying this drug-free signature to 840 samples of patients receiving post-operative tamoxifen therapy, we recognized 553 samples of patients who would have been at high risk of recurrence if they had accepted surgery only and used these samples to develop a tamoxifen therapy benefit predictive signature. The two coupled signatures were validated in independent data. The signatures developed in this study are robust against experimental batch effects and applicable at the individual levels, which can facilitate the clinical decision of tamoxifen therapy.
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