HER2-Positive Metastatic Breast Cancer: Available Treatments and Current Developments

SIMPLE SUMMARY: Since the advent of trastuzumab in HER2-positive metastatic breast cancer management, the natural history of this disease continues to improve. The development of molecular biology and better knowledge of the resistance mechanisms of cancer cells have enabled the development of several therapies targeting HER2 and consequently improved the overall survival of these patients. This paper aims to review the new therapies developed for this entity of breast cancer, their tolerance profiles, and their positions in therapeutic strategy. ABSTRACT: For several years, the overexpression of the HER2 receptor in breast cancer has been correlated with a poor prognosis and an increased risk of developing brain metastases. Currently, the combination of anti-HER2 double blockade and taxane and trastuzumab emtansine (T-DM1) are considered the standard treatments for metastatic breast cancer overexpressing these receptors in the first and second line. Very recently, the development of a new antidrug conjugate, trastuzumab–deruxtecan, has improved the overall survival of patients, even in second-line treatment. However, trastuzumab–deruxtecan has become a new standard. Despite the benefits of these antidrug conjugates, this benefit in patients with brain metastases remains unclear. Tucatinib is a new tyrosine kinase inhibitor that has given hope for the treatment of these patients. The objective of this article was to review data on the established drugs and novel agents for HER2-positive MBC and to discuss how to incorporate anti-HER2 therapies in first and later-line settings.