BACKGROUND Anthracyclines are widely used in the treatment of breast cancer and are well recognised to carry increased risk of cardiotoxicity. This can occur as an early, acute manifestation or many years after treatment as late onset cardiomyopathy. It is increasingly apparent that there may be a chronic subclinical phase associated with low grade cardiac injury with no apparent clinical impact on the contractile function of the heart. This period may remain latent for many years with the patient remaining asymptomatic and with apparently normal cardiac function. Identification of early and subtle cardiac dysfunction during this period could provide a window of opportunity for therapeutic intervention if those at risk or those experiencing this low-grade decline could be accurately identified. This study explores the potential utility of phosphorus magnetic resonance spectroscopy (31P-MRS) to identify very early anthracycline-induced cardiac toxicity and baseline predisposition to cardiac injury. This technique measures the phosphocreatine/adenosine triphosphate concentration ratio (PCr/ATP), which reflects cardiac cellular energetics. The normal range of PCr/ATP is approximately 1.8 - 2.2, whereas decreased PCr/ATP is associated with a drop in available energy reserve in the heart, associated with many forms of heart failure. Conventional cardiac investigations of electrocardiogram, multiple gated acquisition radionuclide scans (MUGA) and ultra-high sensitivity plasma cardiac troponin-I (cTn-I) have also been applied. METHODS 20 newly diagnosed breast cancer patients, receiving anthracycline-based chemotherapy, had magnetic resonance imaging to assess left ventricular ejection fraction and 31P magnetic resonance spectroscopy (31P MRS) to assess phosphocreatine to adenosine triphosphate concentration ratio (“PCr/ATP”). Measurements were performed pre-chemo, mid-chemo and post-chemo. Plasma high sensitivity cardiac troponin-I (cTn-I) and electrocardiograms were performed. RESULTS There was a significant negative correlation between change in PCr/ATP pre- to mid- chemo and change mid- to post-chemo (r=-0.68, p=0.04). Mean ejection fraction reduced significantly (5.1%) pre- to post-chemo (p=0.02). Change in PCr/ATP ratios pre- to post-chemo correlated inversely with changes in LVEF over the same period (r=-0.65, p=0.006) and mid- to post-chemotherapy (r=-0.77, p=0.002). Plasma cTn-I increased pre- to mid-chemo (1.35±0.81 to 4.40±2.64 ng/L; p=0.0001) and mid to post-chemo (4.40±2.64 to 18.33±13.23 ng/L; p=0.0001). CONCLUSIONS This study has demonstrated the use of 31P MRS in exploring cardiac energetics of breast cancer patients undergoing chemotherapy. Pre-chemotherapy PCr/ATP ratios were in line with healthy control values obtained using our system. This technique detected a pattern of recovery of PCr/ATP ratios following an initial 3 cycles of anthracyclines. Changes in PCr/ATP ratios were found to be significantly negatively correlated with changes in LVEF from pre to post chemotherapy. The significant decrease in LVEF from pre-post chemo may be due to the delayed response of LVEF to the initial 3 cycles of anthracyclines. Small but significant increases in plasma levels of cardiac troponin-I were observed early after initiation of anthracyclines. PCr/ATP ratios were not found to be related to cTn-I values but LVEF and cTn-I were found to be positively correlated. Future studies should take account of background factors that could influence cardiac PCr/ATP ratio such as age, physical fitness and regular medication whilst the improved sensitivity of 7T MRI scanners may also help in detecting earlier changes in cardiac energetics in this patient group.

Citation Format: Olga Oikonomidou, Gillian Macnaught Macnaught, Christopher T Rodgers, William Clarke, Annette Cooper, Heather McVicars, Arran K Turnbull, Saeed Mirsadraee, Scott Semple, Martin Denvir. Association of cardiac energetics and plasma biomarkers with anthracycline-based chemotherapy in breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-01-03.