The Emerging Roles of Steroid Hormone Receptors in Ductal Carcinoma in Situ (DCIS) of the Breast

Abstract

Ductal carcinoma in situ (DCIS) is a non-obligate precursor to most types of invasive breast cancer (IBC). Although it is estimated only one third of untreated patients with DCIS will progress to IBC, standard of care for treatment is surgery and radiation. This therapeutic approach combined with a lack of reliable biomarker panels to predict DCIS progression is a major clinical problem. DCIS shares the same molecular subtypes as IBC including estrogen receptor (ER) and progesterone receptor (PR) positive luminal subtypes, which encompass the majority (60–70%) of DCIS. Compared to the established roles of ER and PR in luminal IBC, much less is known about the roles and mechanism of action of estrogen (E2) and progesterone (P4) and their cognate receptors in the development and progression of DCIS. This is an underexplored area of research due in part to a paucity of suitable experimental models of ER+/PR + DCIS. This review summarizes information from clinical and observational studies on steroid hormones as breast cancer risk factors and ER and PR as biomarkers in DCIS. Lastly, we discuss emerging experimental models of ER+/PR+ DCIS.

Progesterone and Breast Cancer: an NCI Workshop Report

“…Dean Edwards presented a ductal carcinoma in situ (DCIS) model using MCF10 DCIS.COM cells engineered with lentiviral vectors to stably express ERalpha, PR-A, and PR-B. Based on gene expression profiling, these cells resemble luminal breast cancer subtypes and are robustly responsive in cell culture to either estrogen or progesterone in terms of regulation of known target genes (57). The cells have also been used successfully in the mouse mammary intraductal xenograft (MIND) system and are responsive to estrogen and progesterone in vivo.…”

Comparing blood versus tissue-based biomarkers expression in breast cancer patients

“…According to histopathological point of view, 80% of the breast tumors are ductal tumors and 10-15% is invasive lobular carcinoma (ILC) [1]. The most important markers have characterized by IHC-based tumor markers in BC, considering three main hormone receptors, including ER, PR and, HER2 [11]. Retrospective studies have demonstrated that patients with ER-and/or PR-containing tumor cells tend to have a better outcome than those without the receptors [11].…”

“…Mammaglobin (MAM) is a protein found in mammary tissue and in the serum, as well. MAM has been proposed as a biomarker to diagnose BC, given that patients exhibit an increased amount of the protein in their serum and tumor tissue compared with healthy individuals [9,10,11,12].…”

Reverse-Phase Protein Array: Technology, Application, Data Processing, and Integration

“…Human DCIS.com cells 24 were engineered to express both ER and PR, and the cell line has been previously characterized as an in vitro model of luminal DCIS that is highly responsive to both estrogen and progesterone. 25 ER and PR are ligand-dependent steroid receptor nuclear transcription factors that act primarily to regulate expression of gene networks. They also mediate rapid effects of steroid hormones on extranuclear proteinsignaling pathways through alteration of protein kinase activity and phosphorylation of protein substrates and downstream events.…”