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From a developmental point of view, tumors can be seen as aberrant versions of their tissue of origin. For example, tumors often partially retain differentiation markers of their tissue of origin and there is evidence that they contain cancer stem cells (CSCs) that drive tumorigenesis. In this review, we summarise current evidence that breast CSCs may partly explain endocrine resistance in breast cancer. In normal breast, the stem cells are known to possess a basal phenotype and to be mainly ERalpha-. If the hierarchy in breast cancer reflects this, the breast CSC may be endocrine resistant because it expresses very little ERalpha and can only respond to treatment by virtue of paracrine influences of neighboring, differentiated ERalpha+ tumor cells. Normal breast epithelial stem cells are highly dependent on the EGFR and other growth factor receptors and it may be that the observed increased growth factor receptor expression in endocrine-resistant breast cancers reflects an increased proportion of CSCs selected by endocrine therapies. There is evidence from a number of studies that breast CSCs are ERalpha- and EGFR+/HER2+, which would support this view. CSCs also express mesenchymal genes which are suppressed by ERalpha expression, further indicating the mutual exclusion between ERalpha+ cells and the CSCs. As we learn more about CSCs, differentiation and the expression and functional activity of the ERalpha in these cells in diverse breast tumor sub-types, it is hoped that our understanding will lead to new modalities to overcome the problem of endocrine resistance in the clinic.

Type

Journal article

Journal

Journal of mammary gland biology and neoplasia

Publication Date

03/2009

Volume

14

Pages

45 - 54

Addresses

Breast Biology Group, School of Cancer and Imaging Sciences, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.

Keywords

Endocrine System, Animals, Humans, Breast Neoplasms, Estrogen Receptor alpha, Epigenesis, Genetic, Drug Resistance, Neoplasm, Neoplastic Stem Cells