Plasma-derived exosomal human epidermal growth factor receptor 2 (HER2) protein for distinguishing breast cancer from benign breast disease and assessing the efficacy of neoadjuvant therapy.

Exosomes derived from liquid biopsy can serve as excellent biomarkers in clinical practices. Human epidermal growth factor receptor 2 (HER2) has been shown to be associated with tumor stage, clinical therapy, and prognosis. However, the clinical value of exosomal HER2 for breast cancer remains unclear. The study aimed to investigate the potential of exosomal HER2 in breast cancer diagnosis, explore its role in guiding clinicians in the selection of treatment options, and find out whether changes in exosomal HER2 levels could be used to evaluate the efficacy of neoadjuvant chemotherapy. The HER2 protein was detected by magnetic particle-based chemiluminescence immunoassay. The study enrolled 51 patients with breast cancer and 36 patients with benign breast disease to evaluate the diagnostic value of exosomal HER2. Additionally, a receiver operating characteristic (ROC) curve was drawn for HER2 immunohistochemistry (IHC) to determine the concordance between exosomal HER2 and HER2 IHC. Furthermore, the exosomal HER2 levels during neoadjuvant therapy were measured to assess the efficacy of neoadjuvant therapy. Exosomal HER2 concentration in patients with breast cancer was significantly higher than that in patients with benign breast disease. The optimal cutoff value of exosomal HER2 for diagnosing breast cancer was 772.7 pg/mL, with a sensitivity of 45.1% and a specificity of 97.22%. With 743 pg/mL as the cutoff value, the concordance between exosomal HER2 levels and HER2 IHC was 74.51%, with a sensitivity of 81.25% and a specificity of 71.43%. Exosomal HER2 could be detected in patients receiving neoadjuvant therapy, and some patients (5/8) exhibited a proportional relationship between exosomal HER2 levels and clinical tumor size changes. Plasma-derived exosomal HER2 might serve as a promising biomarker for distinguishing breast cancer from benign breast disease, screening patients who could benefit from HER2-targeted therapy, and monitoring neoadjuvant therapy.