Experimental models of endocrine responsive breast cancer: Strengths, limitations, and use

Robert Clarke, Brandon C. Jones, Catherine M. Sevigny, Leena A. Hilakivi-Clarke, Surojeet Sengupta

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations


Breast cancers characterized by expression of estrogen receptor-alpha (ER; 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.

Original languageEnglish (US)
Pages (from-to)762-783
Number of pages22
JournalCancer Drug Resistance
Issue number4
StatePublished - 2021

Bibliographical note

Funding Information:
This work was supported by grants from the from the Department of Defense Breast Cancer Research Program (CA171885) and from the National Cancer Institute (U01CA184902) to Dr. Clarke.

Publisher Copyright:
© The Author(s) 2021.


  • Breast cancer
  • Experimental models
  • PDX
  • Study design
  • Xenografts


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