326P - Exploratory analysis of the association of systemic inflammation and breast cancer recurrence in the Optitrain randomised controlled trial

Background

Exercise is suggested to reduce the recurrence risk in individuals with breast cancer. Evidence regarding relevant physiological mechanisms remains scarce. Here, we examined the association of inflammatory biomarkers with predicted recurrence events.

Methods

The Optitrain randomized controlled trial consisted of 240 patients undergoing chemotherapy for primary breast cancer randomised to interventions entailing biweekly supervised concurrent resistance exercise and high-intensity interval training (RT-HIIT), or concurrent aerobic exercise and HIIT (AT-HIIT), or usual care (UC) between 2013-2016. At baseline and the one-year follow-up, 96 inflammatory protein biomarkers were assessed using the Olink® Proximity Extension Assay Oncology Panel. Group differences were estimated using analysis of covariance adjusted for baseline levels. Recurrence outcomes were obtained from National Swedish registers. Event probabilities were predicted from cox-proportional hazards models adjusted for age, menopause, BMI, tumour characteristics, and taxane treatment. Associations between survival probabilities and inflammatory markers were examined using Pearson’s correlation.

Results

When comparing RT-HIIT and UC, exploratory differences across several C-C-motif chemokine ligands were found (CCL2, CCL3, CCL4, CCL13, CCL20, CCL23). Moreover, DCN, ICOSLG, soluble CD8 and CD4, CX3SL1, CXCL10, CD70, CD83, CSF-1, HGF, NCR1, PD-L2, PIGF, PTN, TNFRSF12A, and TNFRSF21S differed across groups (p<0.2). When examining event probabilities, CD70, soluble CD4, CCL2, CCL3, CCL4, CCL13, CCL20, and CCL23 at the one-year follow-up examinations formed a cluster of a weakly increased risk in recurrence-related events. The strongest associations between event probabilities and biomarkers of inflammation were recorded for distant recurrence-free interval events.

Conclusions

Explorative analyses assessing the interplay of systemic inflammation, exercise, and predicted event probabilities suggested a cluster of inflammatory biomarkers affected by exercise and positively correlated with recurrence-related predicted event probabilities.

Clinical trial identification

NCT02522260, August 13, 2015.

Editorial acknowledgement

Legal entity responsible for the study

Region Stockholm.

Funding

1. The Swedish Cancer and Traffic Accident Foundation (CTRF) (grant number F-C-001225) 2. Swedish Cancer Foundation (grant number 130452) 3. Radiumhemmet Research foundation (grant number 131242) 4. Karolinska Institutet School of Caring Sciences (grant number 04960/2012).

Disclosure

All authors have declared no conflicts of interest.