Abstract
BackgroundA 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.MethodsAffymetrix 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.ResultsWe 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.ConclusionsHigh 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.
Highlights
A unique 12-chemokine gene expression score (CS) accurately predicted the presence of tumor-localized, ectopic lymph node-like structures (TL-Ectopic lymph nodes (ELNs)) and improved overall survival (OS) in primary colorectal cancer and metastatic melanoma
Breast cancer is not perceived as a immunogenic tumor when compared with melanoma and renal cell carcinoma as examples, molecular profiling of breast tumors has revealed that a subset demonstrate a high level of immunoregulatory gene activation [4]
Multiple investigators have reported that tumor-infiltrating lymphocytes and certain gene expression profiles related to immune signaling appear to have prognostic and/or predictive implications for breast cancer [especially the human epithelial growth factor receptor 2-positive (HER2+) type] [5,6,7,8,9]
Summary
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. Multiple investigators have reported that tumor-infiltrating lymphocytes and certain gene expression profiles related to immune signaling appear to have prognostic and/or predictive implications for breast cancer [especially the human epithelial growth factor receptor 2-positive (HER2+) type] [5,6,7,8,9]. These studies highlight the potential importance of the immune response in breast cancer patient outcomes. Secretion of chemokines within the tumor microenvironment and how certain co-morbidities like diabetes can affect the tumor chemokine milieu have gained attention as important factors that shape tumor lymphocyte infiltration [10, 11]
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