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Updated: Oct 19, 2025
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Published on: May 18, 2020
Experimental models of endocrine responsive breast cancer: strengths, limitations, and use
Robert Clarke1, Brandon C Jones2, Catherine M Sevigny2,3
1The Hormel Institute and Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Austin, MN 55912, USA.
Abstract:
Breast cancers characterized by expression of estrogen receptor-alpha; ESR1) represent approximately 70% of all new cases and comprise the largest molecular subtype of this disease. Despite this high prevalence, the number of adequate experimental models of ER+ breast cancer is relatively limited. Nonetheless, these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies, and how the ER acts as a transcription factor to regulate cell fate signaling. We discuss the primary experimental models of ER+ breast cancer including 2D and 3D cultures of established cell lines, cell line- and patient-derived xenografts, and chemically induced rodent models, with a consideration of their respective general strengths and limitations. What can and cannot be learned easily from these models is also discussed, and some observations on how these models may be used more effectively are provided. Overall, despite their limitations, the panel of models currently available has enabled major advances in the field, and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.
Insights
Estrogen receptor-positive (ER+) breast cancer models are crucial for understanding endocrine therapy response and resistance. This review details available ER+ breast cancer models, their strengths, and limitations for research.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Estrogen receptor-alpha (ER+) breast cancers are the most prevalent subtype, accounting for approximately 70% of new cases.
- Despite their prevalence, adequate experimental models for ER+ breast cancer remain relatively limited.
- Existing models have been instrumental in understanding cellular responses to endocrine therapies and ER's role in cell fate signaling.
Purpose of the Study:
- To review and discuss the primary experimental models used for studying ER+ breast cancer.
- To evaluate the general strengths and limitations of each model type.
- To provide insights into optimizing the use of these models for future research.
Main Methods:
- Discussion of 2D and 3D cell cultures of established cell lines.
- Review of cell line- and patient-derived xenografts.
- Consideration of chemically induced rodent models.
Main Results:
- The available models, despite limitations, have significantly advanced the understanding of ER+ breast cancer.
- These models facilitate the study of mechanisms underlying therapy action and resistance.
- Models are essential for hypothesis testing that is difficult or unethical in human subjects.
Conclusions:
- A comprehensive panel of experimental models is available for ER+ breast cancer research.
- Understanding the strengths and limitations of each model is key to effective utilization.
- These models remain indispensable for critical research in ER+ breast cancer treatment and resistance mechanisms.
