Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Obstet Gynecol. May 10, 2016; 5(2): 150-161
Published online May 10, 2016. doi: 10.5317/wjog.v5.i2.150
Cancer stem cells and early stage basal-like breast cancer
Pang-Kuo Lo, Benjamin Wolfson, Qun Zhou
Pang-Kuo Lo, Benjamin Wolfson, Qun Zhou, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, United States
Author contributions: Lo PK wrote the manuscript; Wolfson B reviewed and edited the manuscript; Zhou Q designed the aim of the review and reviewed the manuscript.
Supported by The National Cancer Institute (NCI) of National Institutes of Health (NIH) of the United States of America to Zhou Q, Nos. 5R01CA157779-03 and 5R01CA163820-04.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Qun Zhou, MD, PhD, Associate Professor, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 21201, United States. qzhou@som.umaryland.edu
Telephone: +1-410-7061615 Fax: +1-410-7068297
Received: June 28, 2015
Peer-review started: July 11, 2015
First decision: September 17, 2015
Revised: January 13, 2016
Accepted: January 21, 2016
Article in press: January 22, 2016
Published online: May 10, 2016
Abstract

Ductal carcinoma in situ (DCIS) is a category of early stage, non-invasive breast tumor defined by the intraductal proliferation of malignant breast epithelial cells. DCIS is a heterogeneous disease composed of multiple molecular subtypes including luminal, HER2 and basal-like types, which are characterized by immunohistochemical analyses and gene expression profiling. Following surgical and radiation therapies, patients with luminal-type, estrogen receptor-positive DCIS breast tumors can benefit from adjuvant endocrine-based treatment. However, there are no available targeted therapies for patients with basal-like DCIS (BL-DCIS) tumors due to their frequent lack of endocrine receptors and HER2 amplification, rendering them potentially susceptible to recurrence. Moreover, multiple lines of evidence suggest that DCIS is a non-obligate precursor of invasive breast carcinoma. This raises the possibility that targeting precursor BL-DCIS is a promising strategy to prevent BL-DCIS patients from the development of invasive basal-like breast cancer. An accumulating body of evidence demonstrates the existence of cancer stem-like cells (CSCs) in BL-DCIS, which potentially determine the features of BL-DCIS and their ability to progress into invasive cancer. This review encompasses the current knowledge in regard to the characteristics of BL-DCIS, identification of CSCs, and their biological properties in BL-DCIS. We summarize recently discovered relevant molecular signaling alterations that promote the generation of CSCs in BL-DCIS and the progression of BL-DCIS to invasive breast cancer, as well as the influence of the tissue microenvironment on CSCs and the invasive transition. Finally, we discuss the translational implications of these findings for the prognosis and prevention of BL-DCIS relapse and progression.

Keywords: Ductal carcinoma in situ, Invasive ductal carcinoma, Basal-like ductal carcinoma in situ, Basal-like invasive ductal carcinoma, Cancer stem cells

Core tip: Basal-like ductal carcinoma in situ (BL-DCIS) often lacks endocrine receptors and has a high rate of recurrence due to no available targeted therapies. BL-DCIS is a precursor of invasive basal-like breast carcinoma, a malignant cancer prone to metastasis and drug-resistance. Therefore, targeting BL-DCIS to prevent transition into invasive cancer is of significant interest. The recent identification and characterization of cancer stem-like cells in BL-DCIS advance the understanding of BL-DCIS and their potential role in driving the progression of BL-DCIS to invasive basal-like breast cancer. These findings provide critical implications for the development of therapies that prevent the progression of BL-DCIS.