(CCSP076) PENTRAXIN-3 AS A NOVEL CARDIOTOXIC BIOMARKER FOR BREAST CANCER PATIENTS RECEIVING ANTHRACYCLINES AND THE IMPACT OF PHYSICAL ACTIVITY: AN INTERIM REPORT FROM THE EXACT 2.0 TRIAL

Background: Breast cancer patients treated with anthracyclines can experience cardiotoxicity (CTX). Developing strategies to protect against CTX are needed, as is the discovery of sensitive, novel biomarkers to predict CTX. This study’s main objectives were to explore how home-based aerobic exercise can mitigate changes in cardiac function during anthracycline treatment, to explore novel metabolomic and inflammatory biomarkers of CTX, and to examine how the relationship between these biomarkers and cardiac function might be impacted by exercise.

METHODS AND RESULTS: A total of 17 adult females (mean age=50±10 years) enrolled in this trial entitled EXercise to prevent AnthraCycline-based Cardio-Toxicity (EXACT 2.0). Each participant had breast cancer (stages I-III) and was scheduled to receive anthracyclines. Participants underwent a transthoracic echocardiogram to measure left ventricular ejection fraction (LVEF) and percent global longitudinal strain (GLS). Participants also completed the International Physical Activity Questionnaire to assess physical activity levels and provided a blood sample before and after the study. Participants were randomized to receive a 24-week, 2x/week moderate intensity aerobic exercise program or standard of care. Plasma was analyzed using hydrophilic interaction liquid chromatography-mass spectrometry-based targeted metabolomics, and a multiplex magnetic bead inflammatory assay. Measures of LVEF and GLS tended to worsen between the baseline assessment and after the 24-week intervention globally (p=0.075 and 0.066, respectively). Notably, both groups had similar activity levels throughout the 24-weeks (p=0.381), which may explain why exercise did not affect the changes in LVEF or GLS (p>0.16 for each interaction). Overall, a total of 4 metabolic markers and 6 inflammatory markers changed following anthracycline treatment (p < 0.05 for all). Of these, the strongest biomarker of anthracycline induced CTX was Pentraxin-3, where higher levels related to worse LVEF and GLS scores (p=0.007 and 0.048; Figure 1). After adjusting for baseline GLS levels, Pentraxin-3 levels negatively moderated the relationship with GLS levels after anthracycline treatment (Table 1). This may suggest that as physical activity levels increase, the relationship between Pentraxin-3 and LVEF and GLS is mitigated.

Conclusion: These results suggest that higher levels of Pentraxin-3 related to worse cardiac function and that a 24-week moderate intensity aerobic exercise program did not impact changes in LVEF or GLS in breast cancer patients receiving anthracyclines, but results may be masked by a lack of difference in physical activity between study groups.