Evolution of Targeted Therapy in Breast Cancer: Where Precision Medicine Began

During the past decade, a large amount of the research effort within the field of oncology has been devoted to the development and use of targeted therapy. Great strides have been made in our understanding of which patients are appropriate candidates for certain types of treatments (immunotherapy and PARP inhibitors are good examples), and many national and international trials are under way to identify useful targeted therapies for patients with chemotherapy-resistant and/or advanced-stage disease. We have made a lot of progress, but we still have a long way to go in terms of optimizing our ability to identify targeted therapy candidates. Understanding the past can help us shape the future, and, as we look to improve our approaches to targeted therapy across the spectrum of malignancies, the history of targeted therapy in breast cancer therapy can serve as an extremely relevant case study. Breast cancer is one of the first malignancies for which targeted therapies have been used successfully. Endocrine therapies that target the estrogen (ER) and progesterone receptor have long been the cornerstone of systemic therapy approaches for hormone receptor–positive breast cancer, and the discovery of HER2 overexpression has led to the development of multiple HER2-targeted agents that have revolutionized the way HER2-positive breast cancer is treated. Both of these targeted approaches have drastically improved outcomes for these patients. Now, with decades of successful anti-estrogen and now anti-HER2–directed therapy to build upon, our understanding of resistance to targeted therapy is becoming more nuanced. Current clinical trials in breast cancer focus on combating and preventing resistance to targeted therapy, both in the advanced stage as well as in the curative setting. Here, we offer some insights into the history of endocrine therapy and HER2-directed therapy for breast cancer, as well as a discussion of some of the more current developments in this field. It is our hope that this perspective is helpful not only to those with a focus on breast cancer and breast disease but also for those with a broader interest in precision medicine. ENDOCRINE THERAPY Section: ChooseTop of pageAbstractENDOCRINE THERAPY <