343P - Modulation of the immune system (ImS) during moderate physical activity (mPA) in breast cancer (BC) patients (pts) treated with neoadjuvant chemotherapy (NACT)

Background

The link between mPA and ImS is known. We studied the effect of mPA on a panel of circulating cytokines (Cy) during NACT in BC pts.

Methods

Pts underwent epirubicin and cyclophosphamide, followed by weekly paclitaxel ± trastuzumab. Blood samples were collected in pts underwent mPA (TR, Nordic or fit walking, 3 workouts/week, 1 hour each in the 10-12 weeks before surgery) and in pts who declined mPA (UN) at T0, at day 1 of week 6 of paclitaxel (T1, starting point of mPA) and before surgery (T2). 22 Cy: IL1b, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12, IL13, IL15, IL17a, IL18, IL21, CCL2, CCL4, CXCL10, CCL22, IFNγ, TGFβ, TNFα, VEGF were measured by Simple Plex Ella^TM. Differences between the median Cy values were analyzed with Mann-Whitney U test. Comparisons between time points within the same group were analyzed with Wilcoxon signed-rank test. ROC analysis was performed to highlight relevant variables for TR and UN. PCA and PERMANOVA evaluated the impact of mPA on Cy at T1 and T2.

Results

91 pts have been accrued. 88 pts have been analysed, 68 TR and 20 UN. At T0 IL4 was higher (p < 0.01) in UN pts. At T1 IL4 and IL17 were higher (p < 0.01) in UN. At T2 higher values (p < 0.01) of IL4, IL7, IL17, VEGF in UN. Higher IL21 (p < 0.01) in TR. Longitudinal analysis (LA) between T0 and T1 in TR and UN showed increase of INF-γ, IL5, IL15, CCL2, CXCL10, IL17α. UN pts showed also increase of IL6. TR pts showed increase of IL7, IL18 and decrease of IL4, IL13, CCL22. LA between T1 and T2 showed increase of IL21, CCL22, TNFα and decrease of IL6, IL8, IL15 TGFβ in TR pts. UN showed increase of CXCL10 and decrease of IFNγ, IL6, IL8, CCL2, TGFβ. PCA discriminated TR from UN pts at T2 (p=0.045 PERMANOVA analysis).

Conclusions

TR and UN pts were similar at T0. LA between T0-T1 showed that CT induced prominent changes in TR suggesting a more plastic ImS. LA between T1-T2 showed significant changes of Cy only in TR supporting a role of mPA in the modulation of the ImS. Overall, CT induced weak changes in UN and more consistent changes in TR pts, suggesting a more efficient ImS and a possible additional effect derived from mPA in TR. PCA at T2 supports these hypotheses showing a significant grouping of TR clearly separate from UN.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

O. Garrone.

Funding

Fondazione IRCCS Ca' Granda Ospedale maggiore Policlinico, Milan.

Disclosure

O. Garrone: Financial Interests, Personal, Advisory Board: Eisai, Daiichi Sankyo; Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis, Lilly. G. Tomasello: Financial Interests, Personal, Advisory Board: Novartis, Lilly, Amgen. All other authors have declared no conflicts of interest.