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Breast Cancer Research
Published in: Breast Cancer Research 1/2017

Open Access 01-12-2017 | Research article

Evaluation of invasive breast cancer samples using a 12-chemokine gene expression score: correlation with clinical outcomes

Authors: Sangeetha Prabhakaran, Victoria T. Rizk, Zhenjun Ma, Chia-Ho Cheng, Anders E. Berglund, Dominico Coppola, Farah Khalil, James J. Mulé, Hatem H. Soliman

Published in: Breast Cancer Research | Issue 1/2017

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Abstract

Background

A unique 12-chemokine gene expression score (CS) accurately predicted the presence of tumor-localized, ectopic lymph node-like structures (TL-ELNs) and improved overall survival (OS) in primary colorectal cancer and metastatic melanoma. We analyzed the correlation between CS, clinicopathological variables, molecular data, and 366 survival in Moffitt Cancer Center’s Total Cancer Care (TCC) patients with non-metastatic breast cancer.

Methods

Affymetrix gene expression profiles were used to interrogate the CS by the principal component method. Breast tumors were classified as high or low score based on median split, and correlations between clinicopathologic variables, PAM50 molecular subtype, and ELN formation were analyzed using the TCC dataset. Differences in overall survival (OS) and recurrence-free survival (RFS) in the larger KM Plot breast cancer public datasets were compared using Kaplan-Meier curves.

Results

We divided the Total Cancer Care (TCC) breast cancer patients into two groups of high or low CS. Mean CS was 0.24 (range, 2.2–2.1). Patients with higher CS were more likely to be white (172 vs. 159; p = 0.03), had poorly differentiated tumors (112 vs. 59; p <0.0001), ER/PR negative (41 vs. 26) and HER2 positive (36 vs. 19; p = 0.001), and contain TL-ELNs. Higher CS scores were also seen in the basal and HER2+ molecular subtypes. In the KM Plot breast cancer datasets higher CS patients demonstrated superior OS (HR = 0.73, p = 0.008) and RFS (HR 0.76, p = <0.0001), especially in basal and HER2+ patients.

Conclusions

High CS breast tumors tend to be higher grade, basal or HER2+, and present more frequently in Caucasians. However, this group of patients also shows the presence of TL-ELNs within the tumor microenvironment and has better survival outcomes. The CS is a novel tool that can identify breast cancer patients with tumors of a unique intratumoral immune composition and better prognosis. Whether or not the CS is a predictive response marker in breast cancer patients undergoing immunotherapy remains to be determined.
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Metadata
Title
Evaluation of invasive breast cancer samples using a 12-chemokine gene expression score: correlation with clinical outcomes
Authors
Sangeetha Prabhakaran
Victoria T. Rizk
Zhenjun Ma
Chia-Ho Cheng
Anders E. Berglund
Dominico Coppola
Farah Khalil
James J. Mulé
Hatem H. Soliman
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2017
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-017-0864-z

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