With the introduction of mammography coupled with improved treatment, breast cancer mortality rates have decreased 1.8 to 3.4% per year since 1990 ( Hendrick et al., 2019). In 2018, there were about 2.1 million newly diagnosed cases worldwide ( Bray et al., 2018). With the exception of non-melanoma skin cancer, breast cancer is the most frequently diagnosed malignant disease among women ( Bray et al., 2018). In this review we summarize relevant literature on mechanisms associated with breast cancer plasticity, tumor progression, and drug resistance. Understanding the cellular and molecular mechanisms that regulate breast cancer cell plasticity is essential for understanding the biology of breast cancer progression and for developing novel and more effective therapeutic strategies for targeting metastatic disease. Numerous signaling pathways, including MAPK, PI3K, STAT3, Wnt, Hedgehog, and Notch, amongst others, play a critical role in maintaining cell plasticity in breast cancer.
Increases in stemness or epithelial-to-mesenchymal transition (EMT) in primary breast cancer cells lead to enhanced plasticity, enabling tumor progression, therapeutic resistance, and distant metastatic spread. While targeted therapies exist for breast cancer patients with particular subtypes of the disease (Her2+ and ER/PR+), even in these subtypes the therapies are often not efficacious once the patient's tumor metastasizes. Thus, even with improved early screening and more targeted treatments which may enable better detection and control of early disease progression, metastatic disease remains a significant problem. With the exception of non-melanoma skin cancer, breast cancer is the most frequently diagnosed malignant disease among women, with the majority of mortality being attributable to metastatic disease.
2Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.1Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
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