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Inflammatory Responses to Neoadjuvant Chemotherapy Can Be Regulated by Moderate Physical Exercise Prior to Surgery

Conference Correspondent 

Neoadjuvant chemotherapy (NACT) is an important treatment option for patients with early-stage cancer who may benefit from additional systemic treatments prior to undergoing surgery or radiation therapy. Physical activity has been shown to trigger immune responses, but the specific mechanism that mediates these responses in patients with breast cancer has not been determined. Investigators sought to identify the modulators of the immune effects of moderate physical activity (MPA) in patients with breast cancer undergoing NACT prior to surgery.

A total of 27 of 46 patients were treated with 4 cycles of epirubicin and cyclophosphamide followed by paclitaxel for 12 weeks before undergoing surgery. Concentrations of 17 cytokines were measured from blood samples taken at 4 time points: before initiation of chemotherapy (T0), day 1 of week 6 of paclitaxel treatment but before MPA (T1), and before (T2) and after (T3) surgery. Ten patients in the MPA group were required to complete three 1-hour workouts each week for 9 weeks before surgery. The other 17 patients were not prescribed any specific MPA regimen. Another cohort of 15 healthy participants served as an additional comparison group.

Blood samples showed a significant increase in 5 of the 17 cytokines (IFN-gamma, IL-5, CCL-2, and CXCL-10) from before chemotherapy (T0) to before initiation of MPA (T1) in both cohorts receiving NACT. In the group that was not engaging in MPA, CXCL-10 was also significantly increased from before initiation of MPA (T1) to before surgery (T2). Compared with the non-MPA group, the MPA cohort showed a significant decrease in IL-6, IL-13, and CCL-2 before surgery, a decrease in IL-5 during the span between surgery, and an increase in IL-15 after surgery. Interestingly, the immunologic profile of the MPA group was similar to that of healthy individuals before surgery but diverged after surgery. The profile of the non-MPA group was consistently different from healthy participants.

These data demonstrate NACT upregulated proinflammatory cytokines, and this effect was reduced in patients undergoing moderate physical activity. Immunologic analysis of 17 cytokines indicates patients who engage in moderate physical activity have a reduced inflammatory response to NACT before surgery. Only IL-5 was decreased in the MPA cohort after surgery was completed. The immune profiles of patients with breast cancer with a 150-minute/week exercise regimen were similar to healthy individuals, suggesting the potential benefit of MPA for this patient population. However, it should be noted that the beneficial effect of MPA is lost after surgery.

Source: Garrone O, Abbona A, Fallettaet A, et al. Effect of moderate physical exercise on the immune system modulation in patients with breast cancer during preoperative chemotherapy: the NEO-RUNNER study. American Society of Clinical Oncology Virtual Meeting; June 4-8, 2021. Abstract 581.

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