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Review
. 2018;4(1):81-94.
doi: 10.1007/s40778-018-0114-z. Epub 2018 Mar 13.

The Role of Steroid Hormones in Breast and Effects on Cancer Stem Cells

Denis G Alferez  1 , Bruno M Simões  1 , Sacha J Howell  1   2 , Robert B Clarke  1
Affiliations
Review

The Role of Steroid Hormones in Breast and Effects on Cancer Stem Cells

Denis G Alferez et al. Curr Stem Cell Rep. 2018.

Abstract

Purpose of review: This review will discuss how the steroid hormones, estrogen and progesterone, as well as treatments that target steroid receptors, can regulate cancer stem cell (CSC) activity. The CSC theory proposes a hierarchical organization in tumors where at its apex lies a subpopulation of cancer cells endowed with self-renewal and differentiation capacity.

Recent findings: In breast cancer (BC), CSCs have been suggested to play a key role in tumor maintenance, disease progression, and the formation of metastases. In preclinical models of BC, only a few CSCs are required sustain tumor re-growth, especially after conventional anti-endocrine treatments. CSCs include therapy-resistant clones that survive standard of care treatments like chemotherapy, irradiation, and hormonal therapy.

Summary: The relevance of hormones for both normal mammary gland and BC development is well described, but it was only recently that the activities of hormones on CSCs have been investigated, opening new directions for future BC treatments and CSCs.

Keywords: Biomarker; Breast cancer stem cells; Progenitor; Signal pathway; Therapy resistance.

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Conflict of interest statement

Compliance with Ethical StandardsDr. Denis G. Alferez, Dr. Bruno M. Simões, Dr. Sacha J. Howell, and Dr. Robert B. Clarke declare that they have no conflict of interest.This article does not contain any studies with human or animal subjects performed by any of the authors.

Figures

Fig. 1
Fig. 1
Representation of juxtacrine and paracrine signals involved in estrogen and progesterone regulation of BCSCs. Estrogen (E2) and progesterone (Pg) bind to their receptors along with nuclear transcription factors, respectively, regulating expression of downstream target genes. Estrogen sensor cells (non-BCSCs) increase transcription of EGF (epidermal growth factor), AREG (amphiregulin), TGFα (transforming growth factor α), and FGF (fibroblast growth factor), which will signal to the BCSCs through the EGFR and FGFR receptors. Non-BCSCs can also signal with BCSCs via Notch signaling. Progesterone sensor cells (non-BCSCs) upregulate the transcription of several key signaling factors. Regulation of BCSCs via Pg may occur via activation of RANK/RANKL, Wnt receptors/Wnt4, CXCR4/CXCL12, and GHR/GH paracrine signaling (dashed lines). Estrogen and progesterone-induced signals can be blocked by anti-estrogens (e.g., tamoxifen and fulvestrant) and anti-progesterone drugs (e.g., mifepristone and onapristone)
See this image and copyright information in PMC

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