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

• Published in: Breast cancer research : BCR Vol. 19; no. 1; p. 71
• Main Authors: Prabhakaran, Sangeetha, Rizk, Victoria T, Ma, Zhenjun, Cheng, Chia-Ho, Berglund, Anders E, Coppola, Dominico, Khalil, Farah, Mulé, James J, Soliman, Hatem H
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19-06-2017; BioMed Central; BMC
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer therapies; Cell adhesion & migration; Chemokines; Chemokines - genetics; Clinical outcomes; Colorectal carcinoma; Development and progression; Diabetes; ErbB-2 protein; Female; Follow-Up Studies; Gene Expression; Gene Expression Profiling; Gene expression score; Genetic aspects; Humans; Immunology; Immunotherapy; Invasiveness; Kaplan-Meier Estimate; Kinases; Lymph; Lymph nodes; Lymphatic system; Lymphocytes; Medical prognosis; Melanoma; Metastases; Metastasis; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Outcomes; Patients; Physiological aspects; Predictive marker; Principal components analysis; Prognosis; Survival; Survival analysis; Tumor Microenvironment - genetics; Tumors; Young Adult; United States; United States > US; Gene expression score; Breast cancer; Immunology; Chemokines; Outcomes; Predictive marker
• ISSN: 1465-542X; 1465-5411; 1465-542X
• DOI: 10.1186/s13058-017-0864-z

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.
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.
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.
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.