Breaking through to the Other Side: Microenvironment Contributions to DCIS Initiation and Progression

Abstract

Refinements in early detection, surgical and radiation therapy, and hormone receptor-targeted treatments have improved the survival rates for breast cancer patients. However, the ability to reliably identify which non-invasive lesions and localized tumors have the ability to progress and/or metastasize remains a major unmet need in the field. The current diagnostic and therapeutic strategies focus on intrinsic alterations within carcinoma cells that are closely associated with proliferation. However, substantial accumulating evidence has indicated that permissive changes in the stromal tissues surrounding the carcinoma play an integral role in breast cancer tumor initiation and progression. Numerous studies have suggested that the stromal environment surrounding ductal carcinoma in situ (DCIS) lesions actively contributes to enhancing tumor cell invasion and immune escape. This review will describe the current state of knowledge regarding the mechanisms through which the microenvironment interacts with DCIS lesions focusing on recent studies that describe the contributions of myoepithelial cells, fibroblasts and immune cells to invasion and subsequent progression. These mechanisms will be considered in the context of developing biomarkers for identifying lesions that will progress to invasive carcinoma and/or developing approaches for therapeutic intervention.

Long noncoding RNA BHLHE40‐AS1 promotes early breast cancer progression through modulating IL‐6/STAT3 signaling

“…There are currently no known functional determinants of DCIS progression to an invasive lesion; in fact, DCIS and IDC lesions are very similar transcriptionally and epigenetically . This study profiles global lncRNA expression in a unique patient‐based model of breast cancer progression wherein early DCIS lesions are directly contiguous with an IDC lesion.…”

Over a century of cancer research: Inconvenient truths and promising leads

“…In light of the SMT's failure to explain carcinogenesis and deliver promised therapeutic successes, a third group of cancer theories has been introduced that combines a cell-based theory with elements of the tissue-based theory to explain the initial steps of carcinogenesis [36,37]. In essence, this latter group of theories retain the core of the SMT while adding the microenvironment in the form of the multiple cell types that surround the single initiating "cancer cell" [64][65][66][67][68]. They claim that either the cancer cell and its descendants "recruit" the cells in their microenvironment to "prosper" or that perturbations in the stroma induce DNA mutations and translocations in the parenchymal cells [69][70][71].…”

A mouse SWATH-MS reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts

“…The MIND model is based on the injection of human breast DCIS cells such as the MCF10DCIS.com cell line into the mouse mammary duct (Figure 4A) [35–37]. Compared to the other breast cancer xenograft models such as mammary fat pad injection, the MIND model has been shown to better recapitulate the mammary gland microenvironment [36], a key regulator of breast cancer progression [31, 38], and is therefore a more clinically relevant model for this disease. In our experiments, MCF10DCIS.com-Luc cells were injected intraductally into the mammary glands of mice where they form tumours that faithfully model the process of DCIS progression over the course of 10 weeks (Figure 4B-D) [35].…”