Sacituzumab govitecan in HER2-negative breast cancer: redefining treatment paradigms
Avinash Khadela, Kashvy R. Morakhia, Nishra H. Shah, Vibha G. Kanjani, Vraj B. Shah, Hetvi Bharadia, Rushabh Kothari, Manthan Merja
Abstract
Human epidermal growth factor 2-negative breast cancer (HER2-BC) is characterized by the lack of HER2 amplification and encompasses triple-negative breast cancer and hormone receptor-positive HER2-negative breast cancer. Triple-negative breast cancer is distinguished by a total lack of estrogen and progesterone receptors, along with the lack of HER2 amplification. While hormone receptor-positive HER2-negative breast cancer is marked by expression of estrogen receptors with or without progesterone receptors. The major drawback of triple-negative breast cancer is the lack of an enforceable biomarker, and that of hormone receptor-positive HER2-negative breast cancer is endocrine therapy resistance. Consequently, these therapeutic failures result in relapse/recurrence, disease progression, and ultimately a poor prognosis. Sacituzumab govitecan is a novel 3rd generation antibody-drug conjugate that selectively blocks trophoblast cell-surface antigen-2, a highly expressed protein in HER2-BC. This review elaborates on the shortcomings of the standard therapeutic regimens in HER2-BC and the role of Sacituzumab govitecan in addressing these limitations. Clinical trials proposing its application in locally advanced HER2-BC have also been included. Furthermore, clinical trials showcasing the combination of Sacituzumab govitecan with numerous therapeutic modalities improving patient survival and quality of life in metastatic disease have also been included in the text.