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Notch promotes breast cancer progression through tumor initiating cell maintenance, tumor cell fate specification, proliferation, survival, and motility. In addition, Notch is recognized as a decisive mechanism in regulating various juxtacrine and paracrine communications in the tumor microenvironment (TME). In this chapter, we review recent studies on stress-mediated Notch activation within the TME and sequelae such as angiogenesis, extracellular matrix remodeling, changes in the innate and adaptive immunophenotype, and therapeutic perspectives.

It has been more than two decades since Notch has been identified as an oncogene in mouse mammary tumor virus-infected mice. Since this discovery, activated Notch signaling and up-regulation of tumor-promoting Notch target genes have been observed in human breast cancer. In addition, high expression of Notch ligands and receptors has been shown to correlate with poor outcome in this malignancy. Notch affects multiple cellular processes including stem cell maintenance, cell fate specification, differentiation, proliferation, motility and survival. Perturbation of these activities is a hallmark of carcinogenesis and evidence continues to accumulate that aberrant Notch activity influences breast cancer progression through these processes.