Abstract P2-12-14: Effect of moderate physical exercise on the immune system modulation in breast cancer patients during preoperative chemotherapy: The NEO-RUNNER study
Authors: Garrone Ornella , Paccagnella Matteo , Ruatta Fiorella , Abbona Andrea , Falletta Antonella , Vanella Paola , Denaro Nerina , Merlano Marco C 
Published: March 2022

Abstract
Background It is known that the biological mechanism underlying the beneficial effects of physical exercise is linked to immune system stimulation. However, immune mechanisms activated by physical activity are not yet fully understood. We tried to investigate the immune effect of moderate physical activity (MPA), nordic or fit walking, during neoadjuvant chemotherapy (NACT) in breast cancer (BC) patients. Methods Patients candidate to NACT were enrolled. NACT consisted of epirubicin and cyclophosphamide for 4 cycles and weekly paclitaxel for 12 weeks. Trastuzumab and carboplatin were added in HER2 positive and high-risk triple negative BC pts, respectively. Blood samples from pts underwent MPA (TR) were collected at baseline (T0), during CT before starting MPA (T1), before surgery (S) (T2) and after S (T3). Samples were also collected in a group of pts not exposed to MPA (UN) at the same timepoints and in 15 healthy volunteers (HV). MPA consisted of 3 workouts per week, 1 hour each, in the 9-10 weeks before S. The immune profile at each timepoint was evaluated measuring the concentration of 17 cytokines (cys) (IL-2, IL-4, IL-5, IL-6, IL-8, IL10, IL-12, IL-13, IL-15, CCL-2, CCL-4, CXCL-10, CCL-22, IFN-γ, TGF-β, TNF-α, VEGF). Differences in the median cys values were analyzed with non-parametric Mann-Whitney U test and Wilcoxon signed-rank test for paired samples. Principal Component Analysis (PCA) and Hierarchical Clustering on Principal Components (HCPC) were performed to cluster subjects using only the cys able to discriminate TR and UN groups, identified by Receiving Operating Curve (ROC) analysis as variables. Results The study is ongoing. Up to now 52 pts have been enrolled and 39 fully analyzed: 18 TR and 21 UN. The present report focuses on MPA effect. A significant increase of IL-2, CXCL-10 and CCL-22 was found from T1 to T2 in TR pts. IL-2 increased also from T1 to T3. At T1 UN had higher levels of IL-4 and TGF-β compared to TR pts. At T2 IL-6, CCL-2, VEGF and TGF- β levels were significantly higher in UN than in TR pts. At T3 IL-8 level was significantly higher in UN compared to TR pts. ROC Analysis identified 6 cys (IL-4, IL-6, IL-8, CCL-2, VEGF and TGF-β). Using them, HCPC identified 7 clusters at T1, 4 at T2 and 3 at T3. At T1 100% of HV was distributed in cluster 1 and 3. Cluster 1 included also 23.8% of TR and 16.7% of UN pts. The remaining clusters contained only UN and TR mixed populations. At T2: cluster 1 included 86.7% HV, 47.6% TR and 11.1% UN pts. Cluster 2 included 27.7% UN, 38.1% TR pts and 13.3% HV. Cluster 3 encompassed 55.5% UN and 14.3% TR pts. At T3 a very large cluster included 93.3% of HV 66.7% of TR and 61.1% of UN pts. Conclusions Longitudinal analysis showed that cys levels were influenced by MPA. Moreover, at T2 several cys were significantly lower in TR compared to UN pts as possible consequence of MPA. Selecting only the best discriminating cys at T1 a small number of TR and UN pts join the cluster of HV. However, the UN group remains substantially constant after MPA while, almost half of TR pts resettled near HV. Intriguingly, the same cys may separate UN from TR pts, suggesting that cys could also contain enough information to identify the two pts groups. In TR pts MPA may help to restore the immune profile similar to that of HV. At T3, the same percentage of TR and UN pts were close to HV indicating that tumor removal damped the cancer related anti-inflammatory status.
Citation Format: Ornella Garrone, Matteo Paccagnella, Fiorella Ruatta, Andrea Abbona, Antonella Falletta, Paola Vanella, Nerina Denaro, Marco C Merlano. Effect of moderate physical exercise on the immune system modulation in breast cancer patients during preoperative chemotherapy: The NEO-RUNNER study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-14.