Abstract P2-08-19: Prognostication of HER family gene expression collaborate with ESR1 expression in patients with triple negative breast cancer
Authors: Kim J-Y , Ahn T , Jung HH , Park K , Do I-G , Kil WH , Kim SW , Lee JE , Nam SJ , Ahn JS , Park YH , Im Y-H 
Published: May 2016

Background: Triple-negative breast cancer (TNBC) consists of heterogeneous sub-population. Although many investigators made an effort to categorize and classify TNBCs using genetic expressions, it is still needed to be defined for prognostication Traditionally, HER family genes have been known to contribute mammalian glands formation and breast cancer generation as well as ESR gene. Moreover, target agents for HER family genes have been already developed. Accordingly, we investigated the expression profiles of HER family genes with ESR in patients with TNBC to categorize into sub-types and determine the prognostic value of HER family genes in search of clinical implications.

Methods : We investigated the results of the nCounter expression assay (NanoString®) for ERBB1, ERBB2, ERBB3, ERBB4 and ESR1 using mRNA extract from paraffin-embedded tumor tissues in 203 patients diagnosed as TNBC. We used the results of nCounter expression assay using 84 TNBC tissues for validation and 52 breast cancer tissues diagnosed as other subtypes to control the expression assay results of these five genes.

Results: Two-hundred and three patients were diagnosed as TNBC from 2000 to 2004 and received adjuvant chemotherapy after curative surgery. Eighty-four TNBC patients for validation set and 52 patients diagnosed as other subtypes for control set were selected from the patients diagnosed as breast cancer from 2005 to 2010 and received curative surgery. Through analyzing 5 genes using the nCounter expression profiles from 203 TNBC tissues, we found that increased expression of ERBB4 was associated with poor prognosis by survival analysis (5 year disease recurrence free survival (DRFS), low vs. high expression [cut-off: median]: 90.1% vs. 80.2%; p =.002). This trend was still remained in validation set composed of TNBC (5 year DRFS, low vs. high expression [cut-off : median]: 61.1% vs. 44.0%), whereas was not observed in other subtypes of breast cancer (44.4% vs. 80.8%). The Kaplan-Meier estimates of the rates of 5 year DRFS in the subgroups classified according to the level of 5 genes expression showed that the group of higher expression of all HER family genes and lower expression of ESR1 gene had dismal prognosis rather than other groups in patients with TNBC (5 year DRFS, this group vs. others: 50.0% vs. 88.2%; p &lt;.001). In a multivariate Cox regression model, ERBB4 expression identified as a useful marker for predicting long-term prognosis in patients with TNBC although other HER family genes and ESR1 expressions did not predict prognosis of TNBC with statistical significance (Table 1).

Impact of the m RNA expression levels of ERBB family and ESR1 on DRFS Hazard Ratio95% CIP-valueStage  &lt;.001I1.0NA IIA1.200.40-3.57 IIB3.751.20-11.74 IIIA5.461.55-9.24 IIIC59.9214.30-251.12 EGFR  .167Low1.0NA High1.690.80-3.55 ERBB2  .057Low1.0NA High0.430.18-1.03 ERBB3  .061Low1.0NA High2.200.96-5.04 ERBB4  .016Low1.0NA High2.681.20-5.95 ESR1  .113Low1.0NA High0.570.28-1.15 

Conclusions: The expression profile of HER family genes could be used as a prognostic marker in patients with TNBC. Further study is needed to identify the expression profiles of HER family gene as predictive marker of HER targeting treatment in patients with TNBC.

Citation Format: Kim J-Y, Ahn T, Jung HH, Park K, Do I-G, Kil WH, Kim SW, Lee JE, Nam SJ, Ahn JS, Park YH, Im Y-H. Prognostication of HER family gene expression collaborate with ESR1 expression in patients with triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-19.