Introduction: Chemotherapy improves clinical outcomes in breast cancer, including survival and disease control, but its use is often limited by adverse effects. 75% of patients reported multiple symptoms during treatment1. Nutrient-based strategies like hydrolysed whey protein and medium-chain triglycerides may help reduce the severity of chemotherapy side effects, such as diarrhoea, nausea and mucositis2. We aimed to explore whether a combined HWP+MCT diet, or either component alone, improves survival, welfare and tumour control during repeated methotrexate (MTX) in the Dark Agouti mammary adenocarcinoma model (DAMA), and which component(s) drive any benefit.
Methods: N=36 female Dark Agouti rats, weighing 140-170g, aged 6-8 weeks were given ad libitum access to one of four diets: Control (AIN93G), MCT, HWP, or MCT+HWP two weeks prior to MTX treatment and until study end. Rats received subcutaneous mammary adenocarcinoma inoculation to both flanks with tumours measured daily via digital callipers ([length×width×depth]×[π/6] cm3). Rats were assessed daily for diarrhoea and weight loss and were euthanised when tumours were >10% BW (tumour endpoint) or weight loss >15% (welfare endpoint).
Results: Survival did not differ between diet groups (Control 11.75 ± 1.35 days; HWP+MCT 12.25 ± 1.25 days; HWP 12.25 ± 1.98 days; MCT 11.63 ± 1.99 days). The test diets did not lead to significant differences in tumour burden trajectories between groups. Diarrhoea was observed across all diet groups, and all test diets significantly reduced the total proportion of rats that experienced any grade diarrhoea (60%) compared to Control diet (90%) but did not impact the severity experienced (P<0.0001, Chi-square).
Conclusions: While our model was effective in maintaining tumour control and animal welfare, the dietary components did not provide any significant improvement in survival and tumour burden outcomes. Future work will focus on additional dietary components that may be more effective for tumour control.