Abstract
Estrogen receptor (ER) is the major driver of most metastatic breast cancers (mBCs). Endocrine therapy (ET) is the most effective treatment for ER + mBC, but its effectiveness is limited by high rates of de novo and acquired resistance. A growing understanding of the biological characteristics and complexity of the ER pathway and the mechanisms of ET resistance has led to the development of a new generation of targeted therapies. One such mechanism is the cell cycle signaling pathways, which lead to the development of cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) that have, in turn, transformed the management of such tumors. Another important mechanism is the alteration of the phosphatidylinositol 3′-kinase/AKT/mammalian target of rapamycin pathway. Drugs targeting each component of these pathways are currently used in clinical practice, and several more are in development. As a result, a myriad of new targeted therapies are consistently being added to the clinical oncologist armamentarium. Navigating the evolving and highly complex treatment landscape of HR + /HER2− mBC remains both an art and a challenge. In this review, we discuss the biological features of HR + /HER2− mBC and the different mechanisms of resistance to ET. We also discuss the management of mBC as the disease changes from endocrine-sensitive to endocrine-resistant.
Original language | English (US) |
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Pages (from-to) | 189-201 |
Number of pages | 13 |
Journal | Breast Cancer Research and Treatment |
Volume | 190 |
Issue number | 2 |
DOIs | |
State | Published - Nov 2021 |
Keywords
- AI
- CDK4/6 inhibitor
- ER+
- Endocrine therapy
- Estrogen receptor positive
- HR+
- Hormone receptor positive
- Metastatic breast cancer
- Review
- SERD
- SERM
ASJC Scopus subject areas
- Oncology
- Cancer Research