Abstract
<h3>Background</h3> Cytotoxic chemotherapy drugs kill cancer cells by inducing apoptosis. Recent reports have shown that cytochrome c release from mitochondria is a key component in the activation of caspases during apoptosis, and this occurs in response to cleavage of Bcl-2 protein on mitochondrial membrane. NO<sup></sup> appears to suppress cytochrome c release from mitochondria by inhibiting Bcl-2 cleavage. Considering the association between NO<sup></sup> and cytochrome c during the process of apoptosis, we determined serum NO<sup></sup>/cyt c ratio after adjuvant chemotherapy to check its clinical utility for assessing efficacy of treatment. <h3>Methods</h3> 60 female patients with histopathologically proven stage II and stage III breast cancer were selected for the study. 30 age-matched female volunteers were selected for comparison. After obtaining prior written consent, 5ml of venous blood was collected before chemotherapy and again 3weeks after receiving first chemotherapy cycle. The serum was separated by centrifugation and was analysed for cytochrome c and NO<sup></sup>. The serum NO<sup></sup> was determined by spectrophotometric method, and serum cytochrome c was determined by sandwich ELISA. <h3>Findings</h3> A significant decrease in serum NO<sup></sup>/cyt c ratio was observed in stage II and stage III patients after the first adjuvant chemotherapy cycle, compared with the NO<sup></sup>/cyt c ratio before chemotherapy and the NO<sup></sup>/cyt c ratio in healthy controls. To test the potential of NO<sup></sup>/cyt c ratio as a biomarker for predicting the efficacy of chemotherapy, cut-off values were determined by ROC curve analysis of serum NO<sup></sup>/cyt c ratio after the first adjuvant chemotherapy cycle. At the cut-off values of 5.79 for stage II and 6.7 for stage III, we found that it was possible to predict the efficacy of chemotherapy with a sensitivity and specificity of 100%. <h3>Interpretation</h3> Serum NO<sup></sup>/cyt c ratio could be useful in the evaluation of chemotherapy treatment efficacy in breast cancer.
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