The effect of moderate physical activity on the immunological profile in breast cancer patients treated with neoadjuvant chemotherapy

Breast cancer is the most frequently diagnosed cancer in women. The most important risk factors are age, reproductive, genetic and hormonal factors, and lifestyle. Treatment depends on the stage and biological features of the disease. In this work we focused on the changes induced by moderate physical activity on some cytokines in breast cancer patients treated with neoadjuvant chemotherapy (NACT), i.e. chemotherapy performed before surgery in order to reduce the tumor volume. In recent years, a huge amount of scientific evidence have shown a correlation between physical activity and the prevention of numerous diseases, including breast cancer. It is known that there is a link between physical activity and the immune system, even if it has not yet been fully studied which mechanisms are activated by physical exercise. However, it must be considered that the physical activity should be moderate and continuous during everyday life. In fact, too intense and discontinuous activity, without sufficient recovery periods could have opposite effects on the immune system. The aim of this study is to demonstrate that moderate physical activity (MPA), nordic or fit walking, may sustain the immune system to support therapy in controlling the disease; for this purpose, the following immunological factors have been determined: - interleukins of the Th1 profile: IL-2, IL-12, IL-15, IL-21; - interleukins of the Th2 profile: IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IFN-γ, TNF-α; - growth factors: TGF-β and VEGF; - chemokines: CCL-2, CCL-4, CXCL-10, CCL-22. We analysed data on 27 patients 10 patients underwent physical activity (trained, TR) and 17 did not (untrained, UN). Blood samples were collected at defined timepoints: baseline (T0), pre-training (T1), pre-surgery (T2) and post-surgery (T3) in both groups and in 15 healthy volunteers (HV) at baseline. The assay was performed by Ella Automated ImmunoAssay, apart from IL-21 evaluation which was analysed by ELISA kit. The cytokine profile was analysed for each patient and compared among the various timepoints, in order to verify the changes induced by physical activity. Frequencies, averages, medians, ranges and standard deviations (SD) were used for the descriptive analysis of the variables in the study. Differences among the median values were calculated by the non-parametric Mann-Whitney U test. Principal Component Analysis (PCA) and Hierarchical Clustering on Principal Components (HCPC) were performed to classify subjects using the cytokines identified by ROC analysis as variables. The analysis were performed using the SPSS statistical package in version 24 and R 3.5.3. 27 patients (10 TR, 17 UN) have been analysed. A significant increase of IFN-γ, IL-5, IL-8, CCL-2 and CXCL-10 from T0 to T1 was found. CXCL-10 increased from T1 to T2 in UN patients. UN had higher IL-6, IL-13, CCL-2 values at T2 and lower IL-15 value at T3 compared to TR. TR had higher IL-21 value at T2 and T3. ROC analysis found 9 cytokines (IL-2, IL-4, IL-5, IL-6, IL-13, IL-15, CCL-2, VEGF, IL-21) which were used in HCPC. We observed 4 and 3 clusters respectively at T1 and T2. In conclusion we can observed that NACT contributes to upregulation of some inflammatory cytokines. TR showed downregulation of IL-6, IL-13 and CCL-2 during MPA. These data suggest that MPA might damp the inflammatory response to NACT. Moreover, after MPA, while more of TR patients approach HV, some of UN patients’ immune profile moves away from that of HV.