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Mechanisms of Endocrine Resistance in Hormone Receptor-Positive Breast Cancer

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Breast Cancer Research and Treatment

Part of the book series: Cancer Treatment and Research ((CTAR,volume 188))

Abstract

Hormone receptor-positive (HR+) breast cancer (BC) accounts for approximately 70% of all breast invasive tumors. Endocrine therapy (ET) represents the standard treatment for HR + BC. Most patients, however, eventually develop resistance to ET, which limits their effectiveness and poses a major challenge for the management of HR + BC. Several mechanisms that contribute to ET resistance have been described. One of the most common mechanisms is the upregulation of alternative signaling pathways that can bypass estrogen dependency, such as activation of the PI3K/Akt/mTOR as well as mitogen-activated protein kinase (MAPK) and the insulin-like growth factor 1 receptor (IGF-1R) pathways. Another common mechanism of endocrine resistance is the acquisition of activating mutations of ESR1, which encodes for the estrogen receptor, that lead to structural changes of the receptor, prevent the binding to anti-estrogen drugs and result in constitutive activation of the receptor, even in the absence of estrogens. Epigenetic changes, such as DNA methylation and histone modifications, can also contribute to ET resistance by altering the expression of genes that are involved in estrogen signaling. Understanding the mechanisms of resistance to ET is crucial for the development of new therapies that can overcome resistance and improve outcomes for patients with HR + BC.

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Authors and Affiliations

  1. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Antonio Marra

  2. Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Dario Trapani

  3. Harvard Medical School, Boston, MA, USA

    Dario Trapani

  4. Breast Cancer Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Emanuela Ferraro

  5. Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy

    Antonio Marra, Dario Trapani & Giuseppe Curigliano

  6. Department of Oncology and Hematology, University of Milan, Milan, Italy

    Giuseppe Curigliano

Authors
  1. Antonio Marra
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  2. Dario Trapani
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  3. Emanuela Ferraro
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  4. Giuseppe Curigliano
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Corresponding author

Correspondence to Antonio Marra .

Editor information

Editors and Affiliations

  1. Department of Medical Oncology, Mohammed VI University Hospital, Oujda, Morocco

    Ouissam Al Jarroudi

  2. Department of Medical Oncology, Mohammed VI University Hospital, Oujda, Morocco

    Khalid El Bairi

  3. Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy

    Giuseppe Curigliano

Ethics declarations

G.C. reported personal fees from AstraZeneca, Ellipses, Daiichi Sankyo (Daiichi), Lilly, Merck, Novartis, Pfizer, Roche, and Seagen; research funding from Merck; and speakers’ fees from Daiichi, Lilly, Novartis, Pfizer, and Seagen outside the submitted work. A.M., D.T. and E.F. declared no conflict of interest.

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Marra, A., Trapani, D., Ferraro, E., Curigliano, G. (2023). Mechanisms of Endocrine Resistance in Hormone Receptor-Positive Breast Cancer. In: Al Jarroudi, O., El Bairi, K., Curigliano, G. (eds) Breast Cancer Research and Treatment. Cancer Treatment and Research, vol 188. Springer, Cham. https://doi.org/10.1007/978-3-031-33602-7_9

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  • DOI: https://doi.org/10.1007/978-3-031-33602-7_9

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  • Online ISBN: 978-3-031-33602-7

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