A subset of in situ breast tumor cell clusters lacks expression of proliferation and progression related markers but shows signs of stromal and vascular invasion

Estrogen promotes reversible epithelial-to-mesenchymal-like transition and collective motility in MCF-7 breast cancer cells

“…While even in estrogen-treated cultures the percentage of fibroblast-like cells is low (≤10%), this number is comparable to the fraction of cells from a primary tumor actively moving in an animal model of experimental breast cancer metastases [34]. Additionally, in some cases of ER-positive human breast cancer focal areas of stromal invasion contain cells with a more elongated shape and several molecular features that distinguish them from the remainder of the tumor [35].…”

Microenvironmental regulation of cancer development

“…Focal breakdown of myoepithelial cell layer and BM at sites of white blood cell infiltration have also been observed in DCIS [66]. Emphasizing the necessity of changes in both in "seed" and "soil" for progression, epithelial cell clusters overlying the disrupted myoepithelial layers were different from adjacent cells within the same duct with respect of ER (estrogen receptor) status, frequency or pattern of LOH and/or MSI, and expression of tumor progression related genes, normal stem cell and proliferation markers, and showed invasion into the stroma and blood vessels-like structures [67][68][69]. Since tumor-stromal interactions are bi-directional, identification of the initiating events requires further study.…”

Novel Stromal Biomarkers in Human Breast Cancer Tissues Provide Evidence for the More Malignant Phenotype of Estrogen Receptor‐Negative Tumors

“…Recent studies support this combined model, as focal myoepithelial cell layer disruptions were found to be associated with higher leukocyte infiltration [21]. Tumor epithelial cells overlying disrupted myoepithelial cells exhibited substantial differences from other epithelial cells in the duct [22]. They were generally estrogen receptor negative with higher proliferation rate, higher frequency of loss of heterozygosity and higher expression of invasion and cell cycle-related genes [21, 23].…”

“…Therefore it is urgently needed to tailor new treatments that target these cancers. Invasive breast tumors display an ER-negative phenotype [22] that is often considered to result from premalignant ER-positive breast cancers by genetic alteration, epigenetic modification [27] or ER proteasome degradation [28]. …”