Abstract ES1-3: Advanced HER2-positive breast cancer: Overcoming treatment resistance

Abstract

Abstract For two decades, HER2 has been an attractive therapeutic target. Anti-HER2 agents have transformed the care of HER2+ breast cancer and greatly improved its outcomes. However, treatment resistance remains a considerable clinical problem, and some patients still recur and progress despite optimal treatment. A particular challenge in advanced HER2+ breast cancer remains to be CNS metastasis. Special attention needs to be given to this devastating event given its serious sequelae, and its prevalence among patients battling this disease. As more agents are being approved in the early setting, improving outcomes in this setting, patients who suffer a recurrence may have more limited options and more resistant disease. The good news is that there is a number of anti-HER2 agents being explore in the advanced setting of HER2+ breast cancer. They fit into three major categories: new or optimized monoclonal antibodies, antibody-drug conjugates, and tyrosine kinase inhibitors. There is also great interest in studying other classes of agents in combination with anti-HER2 treatment, like immune-oncology agents, in this space. The plethora of agents being developed in this setting highlights the importance to understand more about potential mechanisms of resistance. This will help guide development strategies, deliver tailored treatment approaches, and design more effective agents and regimen. Resistance may be the end result of many possible molecular changes that mediate its emergence, and a variety of strategies are needed to elucidate them. That includes comprehensive in depth molecular profiling, as well as functional validation of detected alterations. Moreover, each tumor may have many underlying molecular changes in different cell sub-populations. It is therefore mandatory that development strategies for new agents and combinations should rely on clinical and biologic factors to help improve outcomes for patients with advanced HER2+ breast cancer. Citation Format: Rimawi M. Advanced HER2-positive breast cancer: Overcoming treatment resistance [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES1-3.