An Initial Evaluation of Human Plasma cMLC-1 as a Potential Protein Biomarker for Trastuzumab-Induced Cardiotoxicity, Breast Cancer Screening and Progression

Background Trastuzumab is a targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, trastuzumab-induced cardiotoxicity (TIC) has been reported as a single agent or combined with anthracycline. Methods such as biomarkers for early TIC detection is not available. Blood-based protein biomarker prostate-specific antigen (PSA) for diagnosis, screening, prediction of response to therapy, and disease progression has revolutionized management and outcome of prostate cancer. Nevertheless, no blood biomarkers exist for breast cancer diagnosis or screening. Methods We evaluated for the first time the potentials of cardiac myosin light chain 1(cMLC-1) as a biomarker to predict TIC, screen breast cancer and monitor breast cancer progression. Plasma cMCL-1 was measured quantitatively using enzyme-linked immunosorbent assays (ELISA). Archived paired plasma samples collected before and after trastuzumab treatment from 15 HER2 + patients with or without cardiotoxicity, recently collected unpaired plasma samples from 79 breast cancer patients (40 HER2+, 39 HER2- ) and 46 healthy donors were tested for cMLC-1 levels. Results We found that elevated plasma level of cMLC-1 is associated with cardiotoxicity in 43% of trastuzumab-treated patients. In addition, we demonstrated that elevated plasma cMCL-1 is associated with breast cancer. The cutoff cMLC-1 concentration is estimated to be 44.99 ng/mL with a sensitivity of 59.49% (95%CI: 48.47%-69.63%) and specificity of 71.74% (95%CI: 57.45% -82.68%). We also found that plasma cMCL-1 is more elevated in HER2- than in HER2 + breast cancer patients. As a result, improved sensitivity of 79.49% (95%CI: 64.47%-89.22%) with the specificity of 63.04% (95%CI:48.60%-75.48%) were obtained for cMLC-1 to predict HER2- breast cancer with the cutoff at 37.17 ng/mL. Moreover, we determined that cMLC-1 level was significantly higher in patients with metastatic breast cancer than in patients with non-metastatic breast cancer. Conclusions Here we report the first exploratory human study on the potential of cMLC-1 as a blood protein biomarker for predicting TIC. Additionally, we show our findings which shed light on and filled, to some extent, the gap of knowledge of the potential of cMLC-1 as a blood protein biomarker for screening breast cancer, especially for HER2- breast cancer, and disease progression of breast cancer.