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

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0864-z) contains supplementary material, which is available to authorized users.

Tumor-Associated Tertiary Lymphoid Structures: Gene-Expression Profiling and Their Bioengineering

“…Moreover, we have now demonstrated that solid tumor radiosensitivity across a spectrum of histologies is associated with immune activation as measured by the GES 1 (8). It remains unclear whether TLSs are either only a consequence of an immune response per se or sites of an active immune reaction against the local tissue components.…”

Role of chemokines in ectopic lymphoid structures formation in autoimmunity and cancer

“…CCL21, instead, is predominantly produced in the lymphatic vessels . Overall, a more favorable outcome has been observed in patients with solid cancers, for example, breast cancer, colorectal carcinomam, melanoma, and non‐small cell lung cancer characterized by the presence of ELS within the neoplastic tissue …”

Prognostic nomogram based on immune scores for breast cancer patients

“…Because of comprehensive treatment including immunotherapy, the prognosis of cancer patients has been greatly improved . Therefore, understanding the relationship between the immune system and prognosis is vital to effectively utilize promising immune‐oncology agents …”

“…[3][4][5] Therefore, understanding the relationship between the immune system and prognosis is vital to effectively utilize promising immune-oncology agents. 6 Recently, increasing attention has been focused on the association between tumor microenvironment and the prognosis of cancer, such as breast cancer 7 and gastric adenocarcinoma. 8 It is noticeable that infiltrating immune cells have been associated with tumor growth, invasion and metastasis in some cancers.…”