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PMID: 19252972 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Resistance to endocrine therapy: are breast cancer stem cells the culprits?

Journal of mammary gland biology and neoplasia ·Vol. 14 ·No. 1 ·2009-03-00 ·Pages 45-54

O'Brien CS, Howell SJ, Farnie G, Clarke RB

Abstract

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.

MeSH Terms
Animals Breast Neoplasms/drug therapy,genetics,metabolism,pathology Drug Resistance, Neoplasm/drug effects Endocrine System/drug effects Epigenesis, Genetic Estrogen Receptor alpha/metabolism Humans Neoplastic Stem Cells/drug effects,metabolism,pathology
Chemicals
Estrogen Receptor alpha
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
O'Brien Ciara S
Breast Biology Group, School of Cancer and Imaging Sciences, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
Howell Sacha J
Farnie Gillian
Clarke Robert B
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Article Info
Journal
Journal of mammary gland biology and neoplasia
Abbr.
J Mammary Gland Biol Neoplasia
ISSN
1573-7039
DOI
10.1007/s10911-009-9115-y
Published
2009-03-00
Epub
2009-00-28
Pages
45-54
Language
English
Region
United States
NLM ID
9601804
Subset
IM
Grants
Breast Cancer Now · 2006MAYSF01 · United Kingdom
External Links
PubMed source DOI: 10.1007/s10911-009-9115-y View journal details
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