PET Image Developments for HER2-Positive Breast Cancer

Breast cancer is the most frequently diagnosed cancer among females worldwide. And overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancer is closely associated with poor prognosis. HER2 belongs to the epidermal growth factor receptor family of tyrosine kinases. It promotes a variety of cellular processes including cell growth, differentiation, cell survival, and cell adhesion and migration. Trastuzumab, which has been approved for the targeted therapy of HER2-positive breast cancer, is widely used now. Trastuzumab can downregulate ErbB2 receptors and cause antibody-dependent cell-mediated cytotoxicity. In clinical studies, simultaneous or sequential administration of trastuzumab with chemotherapy can significantly improve survival. However, its efficacy as a single drug has not yet reached the expected value, less than 30% of HER2-positive breast cancer patients have response to first-line trastuzumab treatment, and most of the initial responders eventually develop resistance to trastuzumab. Clinically, tumor size is assessed by imaging to evaluate trastuzumab treatment response, which is often delayed. Patients with high expression of HER2 may greatly benefit from trastuzumab, therefore, the success of HER2 targeted therapy depends on an accurate assessment of HER2 expression. At present, biopsy is routinely used to obtain pathological tissue for assessing HER2 status. However, with great disadvantages, biopsy is invasive and not suitable for repeated operations. In addition, tumor tissue is heterogeneous, as well as biopsy may not be able to reflect the HER2 status of distant metastases. Currently, compared with biopsy, positron emission tomography (PET), with a targeted HER2 probe, allows non-invasive, real-time assessment of whole body HER2 status. This technology will help physicians select patients who may benefit from HER2-targeted therapy and provide alternative treatment options for those who may not have response to it. Then it will save patients the cost and improve the prognosis of patients. Several antibodies and small molecules targeting HER2 have been labeled with different radionuclides for preclinical and clinical PET imaging studies. This review presents the latest advances in clinical molecular imaging using PET for selecting HER2-positive breast cancer.