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Tumor Heterogeneity Confounds and Illuminates: A case for Darwinian tumor evolution

Nature Medicine volume 20, pages 344–346 (2014)Cite this article

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Ovarian hormones such as estrogens play a key part in normal mammary gland development and in breast tumorigenesis. Estrogens mediate their action on mammary epithelial cells via estrogen receptor (ER), a ligand-dependent nuclear steroid hormone receptor encoded by the ESR1 gene. Because the majority (∼70%) of human breast tumors are ER positive and depend on estrogen for growth, the use of selective ER modulators, such as tamoxifen, in ER-expressing tumors was one of the first examples for successful targeted therapy based on the molecular classification of tumors1. Better understanding of ER function led to the development of multiple other targeted agents with different mechanisms of action, allowing for the more effective inhibition of the ER signaling pathway and fewer side effects. Unfortunately, about a third of ER-positive breast cancers are inherently resistant to endocrine therapy, although they may still respond to other drugs with different mechanisms of action, and 30–40% of the initial responders will also eventually progress to resistant disease. Because the options for these patients are limited, understanding what induces endocrine resistance in these tumors has been one of the longest standing and most intense areas of breast cancer research.

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Figure 1: The role of ESR1 mutations in breast cancer endocrine resistance.

Katie Vicari

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  1. Kornelia Polyak is at the Department of Medical Oncology, and Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.,

    Kornelia Polyak

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  1. Kornelia Polyak
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Correspondence to Kornelia Polyak.

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Polyak, K. Tumor Heterogeneity Confounds and Illuminates: A case for Darwinian tumor evolution. Nat Med 20, 344–346 (2014). https://doi.org/10.1038/nm.3518

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