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Abstract
BackgroundTriple-negative breast cancer (TNBC) is known for aggressive biologic features and poor prognosis. Epidermal growth factor receptor (EGFR) overexpression in TNBC indicates poor prognosis. However, there is no previous study of the relationship between expression of the entire human epidermal growth factor receptor (HER) family genes and patient prognosis in TNBC. Accordingly, we investigated the expression profiles of HER family genes in patients with TNBC to determine the prognostic value and clinical implications of HER family expression.MethodsWe used the nCounter expression assay (NanoString®) to measure the expression of EGFR, erb-B2 receptor tyrosine kinase 2 (ERBB2), ERBB3, ERBB4, and estrogen receptor 1 (ESR1) genes using mRNA extracted from paraffin-embedded tumor tissues from 203 patients diagnosed with TNBC. Our data were validated using a separate cohort of 84 TNBC patients.ResultsA total of 203 TNBC patients who received adjuvant chemotherapy after curative surgery from 2000 to 2004 formed the training set. The 84 TNBC patients in the validation consort were selected from breast cancer patients who received curative surgery since 2005 to 2010. Analysis of the expression profiles of the HER family genes in TNBC tissue specimens revealed that increased expression of ERBB4 was associated with poor prognosis according to survival analysis (5-year distant relapse free survival [5Y DRFS], low vs. high expression [cut-off: median]: 90.1 % vs. 80.2 %; p = 0.022). This trend was also observed in the validation set of TNBC patients (5Y DRFS, low vs. high: 69.4 % vs. 44.7 %; p = 0.053). In a multivariate Cox regression model, ERBB4 expression was identified as a indicator of long-term prognosis in patients with TNBC.ConclusionsThe expression profile of ERBB4, a member of the HER family, might serve as a prognostic marker in patients with TNBC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2195-3) contains supplementary material, which is available to authorized users.
Highlights
Triple-negative breast cancer (TNBC) is known for aggressive biologic features and poor prognosis
We found that TNBC in the training and validation cohorts had lower expression of erb-B2 receptor tyrosine kinase 2 (ERBB2), Erb-B2 Receptor Tyrosine Kinase 3 (ERBB3), Erb-B2 Receptor Tyrosine Kinase 4 (ERBB4), and estrogen receptor 1 (ESR1) than non-TNBC subtypes with statistical significance (Additional file 1: Table S1 and Additional file 2: Figure S1)
In this study, we demonstrated the role of human epidermal growth factor receptor (HER) family genes in TNBC and we suggested that the level of ERBB4 expression had potential prognostic value in TNBC
Summary
Triple-negative breast cancer (TNBC) is known for aggressive biologic features and poor prognosis. Epidermal growth factor receptor (EGFR) overexpression in TNBC indicates poor prognosis. There is no previous study of the relationship between expression of the entire human epidermal growth factor receptor (HER) family genes and patient prognosis in TNBC. Triple negative breast cancer (TNBC), defined as the absence of both hormone receptor expression and erb-B2 receptor tyrosine kinase 2 (ERBB2) overexpression, accounts for approximately 15-20 % of all breast cancers [1]. TNBC is diagnosed at a higher stage and Overexpression of the human epidermal growth factor receptor (HER) family members, consisting of epidermal growth factor receptor (EGFR), ERBB2, ERBB3, and ERBB4, is frequently observed in many kinds of human epithelial malignancies [4]. ERBB2 overexpression is the therapeutic target for the monoclonal antibodies trastuzumab and pertuzumab and the tyrosine kinase inhibitor lapatinib [8,9,10,11].
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