Effect of High Intensity Interval Training on Matrix Metalloproteinases in Women with Breast Cancer Receiving Anthracycline-Based Chemotherapy

Kyuwan Lee,Irene Kang,Wendy J Mack,George Salem,Fred Sattler,Joanne Mortimer,Christina M Dieli-Conwright

doi:10.1038/s41598-020-61927-x

Abstract

Anthracycline chemotherapy is commonly used to treat breast cancer yet may increase the level of matrix metalloproteinases (MMP) -2 and -9, which increase the risk of atherosclerosis. While exercise has been shown to reduce the level of MMP in patients with diabetes, high intensity interval training (HIIT) has not been utilized to improve level of MMP in women with breast cancer receiving anthracycline chemotherapy. Thirty women were randomized to either 8-week HIIT or control (CON) group. The CON group was offered the HIIT intervention after 8 weeks. MMP-1, -2 -7, -9, tissue inhibitor of MMP (TIMP) -1, and-2 were measured at baseline and post-intervention. Repeated measures ANCOVA and paired t-test were performed to assess changes in MMP and TIMP. Post-intervention, no significant between-group differences were observed for MMP and TIMP. However, within-group decrease in MMP-9 was observed in the HIIT group [104.3(51.9) to 65.2(69.1); P = 0.01]. MMP-9 in the CON group was not significantly changed [115.5(47.2) to 90.4(67.9);]. MMP-2 significantly increased in both the HIIT group [76.6(11.2) to 83.2(13.1); P = 0.007) and the CON group [69.0(8.9) to 77.6(11.1) P = 0.003). It is unclear whether an 8-week HIIT intervention influences MMP-9 in breast cancer patients undergoing anthracycline chemotherapy. Additional investigations are required to understand the exercise-induced changes in MMP-2 and -9 in women undergoing anthracycline chemotherapy.

Highlights

Anthracycline chemotherapy is commonly used to treat breast cancer yet may increase the level of matrix metalloproteinases (MMP) -2 and -9, which increase the risk of atherosclerosis
While exercise has been shown to reduce the level of MMP in patients with diabetes, high intensity interval training (HIIT) has not been utilized to improve level of MMP in women with breast cancer receiving anthracycline chemotherapy
MMP-2 and -9 are reduced with exercise interventions in patients with type 2 diabetes[17] and breast cancer[18]; other MMPs such as MMP-1, -7, -9, TIMP-1 and -2, have not been determined whether exercise improves the level of MMPs in clinical populations such as type 2 diabetes

Summary

Introduction

Anthracycline chemotherapy is commonly used to treat breast cancer yet may increase the level of matrix metalloproteinases (MMP) -2 and -9, which increase the risk of atherosclerosis. The “on” portion of HIIT typically involves 1–4 minutes performed at 80–90% of peak power output (PPO), followed by the “off ” period (2–3 minutes of active break [10% PPO])[20] This interval-based strategy has been shown to be more effective than moderate continuous intensity aerobic exercise for improving endothelial function among individuals with stroke or coronary artery disease[21,22,23], and reduces liver fat and increases early diastolic filling rate in patients with non-alcoholic fatty liver disease[24]. We hypothesized that a group of participants that performed the 8-week HIIT intervention would demonstrate greater decreases in circulating serum MMP-2 and -9 compared to a group of participants that did not perform HIIT (CON)

Methods

Results

Conclusion