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. 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. 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. 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. Numerous signaling pathways, including MAPK, PI3K, STAT3, Wnt, Hedgehog, and Notch, amongst others, play a critical role in maintaining cell plasticity in breast cancer. 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. In this review we summarize relevant literature on mechanisms associated with breast cancer plasticity, tumor progression, and drug resistance.

中文翻译：

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乳腺癌进展和治疗中的细胞可塑性。

除非黑色素瘤皮肤癌外，乳腺癌是女性中最常诊断出的恶性疾病，大多数死亡归因于转移性疾病。因此，即使改进了早期筛查和更有针对性的治疗，可以更好地检测和控制早期疾病进展，转移性疾病仍然是一个重大问题。虽然针对特定疾病亚型（Her2+ 和 ER/PR+）的乳腺癌患者存在靶向治疗，但即使在这些亚型中，一旦患者的肿瘤转移，治疗通常也无效。原发性乳腺癌细胞干性或上皮间质转化（EMT）的增加导致可塑性增强，从而促进肿瘤进展、治疗耐药和远处转移扩散。许多信号通路，包括 MAPK、PI3K、STAT3、Wnt、Hedgehog 和 Notch 等，在维持乳腺癌细胞可塑性方面发挥着关键作用。了解调节乳腺癌细胞可塑性的细胞和分子机制对于了解乳腺癌进展的生物学以及开发针对转移性疾病的新颖且更有效的治疗策略至关重要。在这篇综述中，我们总结了有关乳腺癌可塑性、肿瘤进展和耐药性相关机制的相关文献。