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Estrogen receptor status heterogeneity in breast cancer tumor: role in response to endocrine treatment

Cancer Gene Therapy volume 30, pages 932–935 (2023)Cite this article

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Abstract

Tumor heterogeneity affects diagnosis, prognosis and response to therapy. Heterogeneity is found in both normal and neoplastic human mammary gland. Indeed, luminal ER-negative cells can give rise to various phenotypes, including ER-negative and ER-positive mammary tumors. As a result, the tumor phenotype does not necessarily reflects the cell of origin of cancer. With regard to the ER status, heterogeneity can challenge endocrine therapies, where the elimination of responsive clones could lead to reduced treatment efficacy and tumor relapse through the expansion of the resistant clones. The aim of this study was to investigate breast tumor heterogeneity and its role in endocrine resistance onset. For this purpose, we used ER+ (T47D, CAMA1) and triple-negative breast cancer cell lines (TNBC; MDA-MB-231, HCC70), co-cultures using 2D and 3D models. Our results showed that ER status is modulated when ER+ cells are cultured in the presence of TNBC cells, leading to a different response to endocrine therapy, demonstrating that the response to treatment can be affected by the influence that different breast cancer cell types exert on each other. In addition, ER+ positive cells doubling time was modified after exposure to TNBC cell co-culturing. Further experiments are required to fully elucidate the molecular mechanism of these observations.

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Fig. 1: Effects of MDA-MB-231 co-culture on CAMA1 cells response to tamoxifen.
Fig. 2: T47D cells reduce HCC70 response to treatment.

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Authors and Affiliations

  1. Department of Medicine, University of Udine, Udine, Italy

    Eleonora Malavasi & Teresa Gagliano

  2. School of Life Sciences, University of Sussex, Brighton, UK

    Georgios Giamas

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  1. Eleonora Malavasi
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  2. Georgios Giamas
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  3. Teresa Gagliano
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Contributions

TG and GG concived the idea. EM and TG performed the experiments. TG and EM wrote the manuscript. TG and GG supervised and directed the project.

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Correspondence to Teresa Gagliano.

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Conflict of interest

Georgios Giamas is editor-in-chief of Cancer Gene Therapy. Teresa Gagliano is an associate editor of Cancer Gene Therapy. No other conflicts are declared. This manuscript went through a standard external peer review process and none of the authors were involved with this.

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Malavasi, E., Giamas, G. & Gagliano, T. Estrogen receptor status heterogeneity in breast cancer tumor: role in response to endocrine treatment. Cancer Gene Ther 30, 932–935 (2023). https://doi.org/10.1038/s41417-023-00618-x

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