Breast cancer is the most frequent cancer among women, and metastases in distant organs are the leading cause of the cancer-related deaths. While survival of early-stage breast cancer patients has increased dramatically, the 5-year survival rate of metastatic patients has barely improved in the last 20 years. Metastases can arise up to decades after primary tumor resection, hinting at microenvironmental factors influencing the sudden outgrowth of disseminated tumor cells (DTCs). This review summarizes how the environment of the most common metastatic sites (lung, liver, bone, brain) is influenced by the primary tumor and by the varying dormancy of DTCs, with a special focus on how established metastases persist and grow in distant organs due to feed-forward loops (FFLs). We discuss in detail the importance of FFL of cancer cells with their microenvironment including the secretome, interaction with specialized tissue-specific cells, nutrients/metabolites, and that novel therapies should target not only the cancer cells but also the tumor microenvironment, which are thick as thieves.

中文翻译：

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转移性癌细胞与其微环境之间的前馈循环——升级阶段

乳腺癌是女性中最常见的癌症，远处器官转移是癌症相关死亡的主要原因。虽然早期乳腺癌患者的生存率大幅提高，但转移性乳腺癌患者的 5 年生存率在过去 20 年中几乎没有提高。原发肿瘤切除后长达数十年可能会出现转移，这暗示微环境因素影响播散性肿瘤细胞（DTC）的突然生长。这篇综述总结了最常见转移部位（肺、肝、骨、脑）的环境如何受到原发肿瘤和 DTC 不同休眠状态的影响，特别关注已建立的转移瘤如何在远处器官中持续存在和生长。前馈循环（FFL）。我们详细讨论了癌细胞及其微环境（包括分泌组、与专门组织特异性细胞的相互作用、营养物/代谢物）的 FFL 的重要性，并且新疗法不仅应针对癌细胞，还应针对肿瘤微环境。作为小偷。