[Application of neratinib in the treatment of hormone receptor and HER-2 double positive breast cancer].

Abstract

Hormone receptor (HR), human epidermal growth factor receptor-2(HER-2) double positive breast cancer is a highly aggressive disease, and it is more susceptible to drug resistance and metastasis. Currently, although anti-HER-2 monoclonal antibody combined with endocrine therapy is commonly used in clinical practice, patients with HR-positive and HER-2-positive still have a poor prognosis. That may be caused by the activation of downstream PI3K/Akt/mTOR signaling pathway of HER-2. Therefore, simultaneously blocking the extracellular, intracellular and downstream PI3K/Akt/mTOR signaling pathway of HER-2, as well as the dual blockade of HER-2 and HR, is more conducive to the treatment of HR positive and HER-2 positive breast cancer. The small-molecule tyrosine kinase inhibitor neratinib not only inhibits the phosphorylation of HER-1, HER-2 and HER-4, but also blocks the downstream signal transduction of PI3K/Akt and Ras/Raf/MEK/ERK pathways. The intensive adjuvant chemotherapy studies has confirmed that nelatinib can improve the prognosis of patients with HER-2 positive breast cancer, especially those with HR and HER-2 double positive patients. Nelatinib has also achieved positive effect on the treatment of advanced breast cancer, but relevant data on the treatment of HR-positive and HER-2 positive advanced breast cancer are still lacking. Lapatinib, a small-molecule HER inhibitor similar to neratinib, has shown some effects on the treatment of HR-positive and HER-2 positive patients with advanced breast cancer. Given that nelatinib has a superior efficacy than lapatinib, it is expected to provide more ideas and options for the treatment strategies of breast cancer.