Research Papers:

Human epidermal growth factor receptor 4 (HER4) is a favorable prognostic marker of breast cancer: a systematic review and meta-analysis

Jue Wang, Jun Yin, Qing Yang, Feng Ding, Xiao Chen, Bingjie Li and Xingsong Tian _

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Oncotarget. 2016; 7:76693-76703. https://doi.org/10.18632/oncotarget.12485

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Jue Wang1, Jun Yin2, Qing Yang1, Feng Ding3, Xiao Chen1, Bingjie Li4, Xingsong Tian1

1Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China

2Department of Systems Biology, MD Anderson Cancer Center, Houston, Texas, USA

3Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China, Department of General Surgery, Jinan Hospital, Jinan, Shandong, China

4Division of Epidemiology, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA

Correspondence to:

Xingsong Tian, email: [email protected]

Keywords: HER4/ErbB-4, breast cancer, meta-analysis, prognosis, marker

Received: June 21, 2016     Accepted: September 21, 2016     Published: October 05, 2016


Based on a large cohort of clinical studies involving a total of 8024 patients and reporting the effects of HER4 on breast cancer prognosis, we conducted the first meta-analysis and review of this type. We identified 26 studies published between 1985 and 2016 and assessed the prognostic value of HER4 in breast cancer by either real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR, for mRNA levels) or immunohistochemistry (IHC, for protein levels). Elevated expression of HER4 was significantly associated with longer relapse-free survival (RFS) (HR = 0.63; CI: 0.48−0.83; P = 0.001, random effects). Further subgroup analysis showed that our results were stable irrespective of subtype [Luminal: HR = 0.40, CI: 0.30−0.53, P < 0.001, fixed effects; triple negative breast cancer (TNBC): HR = 0.49, CI: 0.26−0.90, P = 0.02, fixed effects; and HER2-positive: HR = 0.53, CI: 0.40−0.71, P < 0.001, fixed effects]. Cytoplasmic HER4 was more effective than nuclear HER4 (HR = 0.74, CI: 0.60−0.92, P = 0.007, fixed effects) for predicting RFS. HER4 was also found to be a favorable prognostic marker for overall survival (OS) among patients with non-TNBC in the subgroup analysis (Luminal: HR = 0.71, CI: 0.52−0.95, P = 0.023, fixed effects; HER2-positive: HR = 0.48, CI: 0.26−0.89, P = 0.020, fixed effects).

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