The Changing Landscape of Breast Cancer: How Biology Drives Therapy

Abstract

Breast cancer is the most prevalent life-threatening cancer in women. Optimizing therapy to increase cure rates in early stage disease, and improving life expectancy and palliation for advanced stages, are goals driving major areas of research. The armamentarium of targeted treatments for breast cancer is ever expanding as understanding of breast cancer biology deepens. A revolution in our treatment was heralded a decade ago by the introduction of trastuzumab for human epidermal receptor-2 positive (HER2+) disease resulting in remarkable reductions in recurrence and improvements in overall survival (OS). Advances continue to be made in other breast cancer subtypes targeting key activating pathways for therapeutic development. However, for these other targeted agents, improvement in OS has been elusive. This article focuses on the development of targeted therapy in breast cancer focusing primarily on the last 5 years, to illustrate that as we understand the complex pathways allowing the dysregulated cell to become malignant, it also propels us closer towards the promise of precision and personalized medicine.

Keywords: Ado-trastruzumab-emtansine; PI3K/AKT/mTOR Inhibitors; angiogenesis inhibitors; breast cancer; cyclin-dependent kinase (CDK) inhibitors; pertuzumab; poly (ADP-ribose) polymerases (PARP) inhibitors; targeted therapy.

Figure 1

Unites States Federal Drug Administration (U.S. FDA)-approved drugs (since 2010).

Figure 2

Proposed sequencing strategy for postmenopausal patients with ER+/HER2− advanced breast cancer.