Monocyte-to-lymphocyte ratio as predictor of cancer therapy-related cardiotoxicity in patients with breast cancer: a pilot cohort study.

BACKGROUND: Elevated pre-treatment baseline inflammation has been associated with cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer. Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and systemic immune-inflammation index (NLR × platelets) have emerged in clinical context as markers of disease-related inflammation. OBJECTIVES: To evaluate development of CTRCD according to pre-treatment blood inflammatory biomarkers in patients with breast cancer. METHODS: Pilot cohort study including consecutive female patients ≥ 18 years with HER2-positive early breast cancer who consulted at the institution's breast oncology outpatient clinic between march/2019 and march/2022. CTRCD: absolute reduction in LVEF > 10% to below 53% (2D-echocardiogram). Survival analysis was performed using Kaplan-Meier curves, compared by the log-rank test, and discrimination ability was evaluated through AUC-ROC. RESULTS: Forty-nine patients (53.3 ± 13.3 y) were included and followed-up for a median of 13.2 months. CTRCD was observed in 6 (12.2%) patients. Patients with high blood inflammatory biomarkers had lower CTRCD-free survival (P < 0.050 for all). MLR showed statistically significant AUC (0.802; P = 0.017). CTRCD was observed in 27.8% of patients with high MLR versus 3.2% with low MLR (P = 0.020); negative predictive value was 96.8% (95%CI 83.3-99.4%). CONCLUSION: In patients with breast cancer, elevated pre-treatment inflammatory markers were associated with increased risk of cardiotoxicity. Among these markers, MLR had good discriminatory performance and high negative predictive value. The incorporation of MLR might improve risk evaluation and selection of patients for follow-up during cancer therapy.

Systemic administration of doxorubicin impairs aversively motivated memory in rats.

There is growing clinical evidence of cognitive impairment in cancer patients treated with chemotherapy, especially in women treated with drug combinations for breast cancer. Clinical studies have a difficult task of defining which drugs individually are responsible for the cognitive changes and published papers evaluating single agents in experimental models are scanty. In the present study we have investigated the effect of single escalating doses of doxorubicin (DOX) on memory for inhibitory avoidance conditioning (IA) in rats. The doses used were comparable to those applied in the clinic. When given systemically before training, higher doses of DOX impaired IA memory retention measured 24h and 7days, but not 3h after training. DOX did not affect IA retention when given either before or after training in a multiple-trial IA training protocol. Control experiments showed that DOX produced a decrease in exploratory behavior assessed by the number of rearings performed during exploration of an open field. The results indicate that a single systemic administration of DOX might impair long-term aversive learning.