Abstract 157P
Background
There is a link between PA and the immune system. Immune mechanisms activated by PA in BC have not been fully investigated. We analysed the effect of MPA, nordic or fit walking, during neoadjuvant chemotherapy (NACT) in BC patients (pts).
Methods
Pts received epirubicin and cyclophosphamide for 4 cycles followed by paclitaxel for 12 weeks. Blood samples from pts who underwent MPA (TR) were collected before starting chemotherapy at baseline (T0), at day 1 of week 6 of paclitaxel (before starting MPA) (T1), before surgery (S) (T2) and after S (T3). Samples were also collected in a group of pts who declined MPA (UN) at the same time points 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 was evaluated measuring the concentration of 18 cytokines (cy): IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-21, CCL-2, CCL-4, CCL-22, CXCL-10, VEGF, IFN-γ, TGF-β and TNF-α. Differences among the median values were calculated by non parametric Mann-Whitney U test. Principal Component Analysis (PCA) and Hierarchical Clustering on Principal Components (HCPC) were performed to classify subjects using the cy identified by ROC analysis as variables.
Results
Twenty-seven out of 46 pts (10 TR, 17 UN) have been analysed. A significant increase of IFN-γ, IL-5, IL-8, CCL-2 and CXCL-10 values from T0 to T1 (P<0.01, P=0.01, P=0.03, P=0.04, P=0.04, respectively) was found. CXCL-10 increased from T1 to T2 (P=0.03) in UN pts. UN pts had higher IL-6, IL-13, CCL-2 values at T2 (P=0.01, P=0.04, P=0.02) and lower IL-15 value at T3 (P=0.04) compared to TR. TR pts had higher IL-21 value at T2 (P=0.03) and T3 (P=0.03). ROC analysis found 9 cy (IL-2, IL-4, IL-5, IL-6, IL-13, IL-15, IL-21, CCL-2, and VEGF) which were used in HCPC. At T2, 3 clusters (C) were identified: C1 included 82% UN, 50% TR and 7% HV; C2 86% HV, 50% TR and 12% UN; C3 6% UN and 7% HV.
Conclusions
NACT contributes to upregulation of some inflammatory cy. TR pts 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, our results suggest that, after MPA, some TR pts reach an immune profile similar to HV. Updated results will be presented.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Dr. Ornella Garrone.
Funding
ARCO Foundation.
Disclosure
O. Garrone: Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: EISAI; Financial Interests, Personal, Invited Speaker: Novartis. N. Denaro: Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: BMS. M.C. Merlano: Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Eisai; Non-Financial Interests, Personal, Member of the Board of Directors: Gruppo Oncologico Nord Ovest (GONO). All other authors have declared no conflicts of interest.