142 Cardiac and skeletal muscle energetic pathways following anthracycline chemotherapy for breast cancer

Background/Introduction Anthracycline-related cardiac dysfunction is a recognised consequence of cancer therapies. Here we assess resting and skeletal muscle energic status as an early mechanistic pathway myocyte derangement explore molecular targets metabolism, protein synthesis/degradation mitochondrial biogenesis signalling. Methods We conducted prospective, mechanistic, observational, longitudinal study chemotherapy-naive breast patients undergoing anthracycline-based chemotherapy, compared to healthy control group. 31P-Magnetic Resonance spectroscopy in (phosphocreatine/gamma adenosine triphosphate (PCr/yATP) inorganic phosphate/phosphocreatine (Pi/PCr) ratios respectively), magnetic resonance (CMR) imaging inclusive T1 T2 mapping, echocardiography-derived global strain function, serum NT-pro-BNP biopsies from the right vastus lateralis were assessed before after 3 cycles Flurouracil, Epirubicin Cyclophosphamide followed by Docetaxel. Statistical significance was set at p<0.05. Results Twenty-five female (median age 53 years, range 32 – 74 years) receiving mean epirubicin dose 307 mg/m2) twenty-eight controls 44 23 - 65) recruited. All assessments pre-chemotherapy stage comparable matched controls. However, following demonstrated small but significant reduction function (global -22.9 ± 3.9 vs -19.1 3.3 %, p=0.01 CMR-derived ejection fraction 65 5 62 4 p=0.047), mild increase indexed left ventricular volumes (end diastolic 10 11 ml/m2, p=0.014 end systolic 28 p=0.01) well T2-mapping (1289 29 1321 31 ms, p=0.004 50 55 7 p=0.027, respectively) NT-Pro-BNP (49 25 108 84 pg/m, p=0.008). After epirubicin, there PCr/yATP ratio (2.0 0.7 1.2 0.6, p=0.007) Pi/PCr (0.13 0.04 0.22 0.2, p=0.008) Figure 1. Following upregulation synthesis (mammalian target rapamycin, 0.44 0.4 0.53 p<0.001) degradation (Calcium/calmodulin dependent kinase II, 1.4 2.7 1.1, p<0.001), metabolism (peroxisome proliferator-activated receptor gamma, 0.35 0.2 0.60 0.1, mass regulator myostatin-2 (0.16 0.1 0.24 p<0.001). Conclusion Contemporary doses for result high energy 31P-metabolism alongside myocellular alterations metabolic regulation pathways. Conflict Interest None