The E2F4 prognostic signature predicts pathological response to neoadjuvant chemotherapy in breast cancer patients

BMC Cancer

Research Article

Kenneth M. K. Mark¹  Matthew H. Ung¹  Frederick S. Varn¹  Chao Cheng²  Feng Qian³ 

[1] Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, 03755, Hanover, NH, USA;Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, 03755, Hanover, NH, USA;Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, 03766, Lebanon, NH, USA;Norris Cotton Cancer Center, 03766, Lebanon, NH, USA;Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, 200438, Shanghai, China;

关键词: Breast cancer;    Neoadjuvant chemotherapy;    ChIP-seq;    Transcription factor;    E2F4;    Pathologic complete response;   

DOI  :  10.1186/s12885-017-3297-2

 received in 2016-03-15, accepted in 2017-04-24,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundNeoadjuvant chemotherapy is a key component of breast cancer treatment regimens and pathologic complete response to this therapy varies among patients. This is presumably due to differences in the molecular mechanisms that underlie each tumor’s disease pathology. Developing genomic clinical assays that accurately categorize responders from non-responders can provide patients with the most effective therapy for their individual disease.MethodsWe applied our previously developed E2F4 genomic signature to predict neoadjuvant chemotherapy response in breast cancer. E2F4 individual regulatory activity scores were calculated for 1129 patient samples across 5 independent breast cancer neoadjuvant chemotherapy datasets. Accuracy of the E2F4 signature in predicting neoadjuvant chemotherapy response was compared to that of the Oncotype DX and MammaPrint predictive signatures.ResultsIn all datasets, E2F4 activity level was an accurate predictor of neoadjuvant chemotherapy response, with high E2F4 scores predictive of achieving pathologic complete response and low scores predictive of residual disease. These results remained significant even after stratifying patients by estrogen receptor (ER) status, tumor stage, and breast cancer molecular subtypes. Compared to the Oncotype DX and MammaPrint signatures, our E2F4 signature achieved similar performance in predicting neoadjuvant chemotherapy response, though all signatures performed better in ER+ tumors compared to ER- ones. The accuracy of our signature was reproducible across datasets and was maintained when refined from a 199-gene signature down to a clinic-friendly 33-gene panel.ConclusionOverall, we show that our E2F4 signature is accurate in predicting patient response to neoadjuvant chemotherapy. As this signature is more refined and comparable in performance to other clinically available gene expression assays in the prediction of neoadjuvant chemotherapy response, it should be considered when evaluating potential treatment options.

【 授权许可】

CC BY   
© The Author(s). 2017