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Management of hormone receptor–positive, human epidermal growth factor 2–negative metastatic breast cancer

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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.

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Acknowledgements

The authors received no funding or financial support for the authorship or publication of this article. This article has been reviewed and proofread by the Editing Services, Research Medical Library at the University of Texas MD Anderson Cancer Center.

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  1. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Jason A. Mouabbi

  2. Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, 7200 Cambridge St., Suite 7A, Houston, TX, 77030, USA

    C. Kent Osborne, Rachel Schiff & Mothaffar F. Rimawi

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JM wrote this review under the direct input and guidance of CKO, RS, and MR.

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Mouabbi, J.A., Osborne, C.K., Schiff, R. et al. Management of hormone receptor–positive, human epidermal growth factor 2–negative metastatic breast cancer. Breast Cancer Res Treat 190, 189–201 (2021). https://doi.org/10.1007/s10549-021-06383-5

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