Advances in Preventive Therapy for Estrogen-Receptor-Negative Breast Cancer.

Preventing breast cancer is an effective strategy for reducing breast cancer deaths. The purpose of chemoprevention (also termed preventive therapy) is to reduce cancer incidence by use of natural, synthetic, or biological agents. The efficacy of tamoxifen, raloxifene, and exemestane as preventive therapy against estrogen-receptor (ER)-positive breast cancer is well established for women at increased risk for breast cancer. However, because breast cancer is a heterogeneous disease, distinct preventive approaches may be required for effective prevention of each subtype. Current research is, therefore, focused on identifying alternative mechanisms by which biologically active compounds can reduce the risk of all breast cancer subtypes including ER-negative breast cancer. Promising agents are currently being developed for prevention of HER2-positive and triple-negative breast cancer (TNBC) and include inhibitors of the ErbB family receptors, COX-2 inhibitors, metformin, retinoids, statins, poly(ADP-ribose) polymerase inhibitors, and natural compounds. This review focuses on recent progress in research to develop more effective preventive agents, in particular for prevention of ER-negative breast cancer

Advances in Preventive Therapy for Estrogen-Receptor-Negative Breast Cancer.

Preventing breast cancer is an effective strategy for reducing breast cancer deaths. The purpose of chemoprevention (also termed preventive therapy) is to reduce cancer incidence by use of natural, synthetic, or biological agents. The efficacy of tamoxifen, raloxifene, and exemestane as preventive therapy against estrogen-receptor (ER)-positive breast cancer is well established for women at increased risk for breast cancer. However, because breast cancer is a heterogeneous disease, distinct preventive approaches may be required for effective prevention of each subtype. Current research is, therefore, focused on identifying alternative mechanisms by which biologically active compounds can reduce the risk of all breast cancer subtypes including ER-negative breast cancer. Promising agents are currently being developed for prevention of HER2-positive and triple-negative breast cancer (TNBC) and include inhibitors of the ErbB family receptors, COX-2 inhibitors, metformin, retinoids, statins, poly(ADP-ribose) polymerase inhibitors, and natural compounds. This review focuses on recent progress in research to develop more effective preventive agents, in particular for prevention of ER-negative breast cancer

Constitutively Active Type I Insulin-Like Growth Factor Receptor Causes Transformation and Xenograft Growth of Immortalized Mammary Epithelial Cells and Is Accompanied by an Epithelial-to-Mesenchymal Transition Mediated by NF-κB and Snail▿

Type I insulin-like growth factor receptor (IGF-IR) can transform mouse fibroblasts; however, little is known about the transforming potential of IGF-IR in human fibroblasts or epithelial cells. We found that overexpression of a constitutively activated IGF-IR (CD8-IGF-IR) was sufficient to cause transformation of immortalized human mammary epithelial cells and growth in immunocompromised mice. Furthermore, CD8-IGF-IR caused cells to undergo an epithelial-to-mesenchymal transition (EMT) which was associated with dramatically increased migration and invasion. The EMT was mediated by the induction of the transcriptional repressor Snail and downregulation of E-cadherin. NF-κB was highly active in CD8-IGF-IR-MCF10A cells, and both increased levels of Snail and the EMT were partially reversed by blocking NF-κB or IGF-IR activity. This study places IGF-IR among a small group of oncogenes that, when overexpressed alone, can confer in vivo tumorigenic growth of MCF10A cells and indicates the hierarchy in the mechanism of IGF-IR-induced EMT