Castaño Zafira, Tracy Kristin, McAllister Sandra S
Department of Medicine, Hematology Division, Brigham and Women's Hospital, Harvard Medical School, 1 Blackfan Circle, Boston, MA 02115, USA.
Int J Dev Biol. 2011;55(7-9):889-97. doi: 10.1387/ijdb.113366zc.
Breast cancer is the most common malignancy among women worldwide and is the most common cause of death for women between 35 and 50 years of age. Women with breast cancer are at risk of developing metastases for their entire lifetime and, despite local and systemic therapies, approximately 30% of breast cancer patients will relapse (Jemal et al., 2010). Nearly all breast cancer related deaths are due to metastatic disease, even though metastasis is considered to be an inefficient process. In some cases, tumor cells disseminate from primary sites at an early stage, but remain indolent for protracted periods of time before becoming overt, life-threatening tumors. Little is known about the mechanisms that cause these indolent tumors to grow into malignant disease. Because of this gap in our understanding, we are unable to predict which breast cancer patients are likely to experience disease relapse or develop metastases years after treatment of their primary tumor. A better understanding of the mechanisms and signals involved in the exit of tumor cells from dormancy would not only allow for more accurate selection of patients that would benefit from systemic therapy, but could also lead to the development of more targeted therapies to inhibit the signals that promote disease progression. In this review, we address the systemic, or "macroenvironmental", contribution to tumor initiation and progression and what is known about how a pro-tumorigenic systemic environment is established.
乳腺癌是全球女性中最常见的恶性肿瘤，也是35至50岁女性最常见的死因。乳腺癌患者一生中都有发生转移的风险，尽管进行了局部和全身治疗，但仍有大约30%的乳腺癌患者会复发（Jemal等人，2010年）。几乎所有与乳腺癌相关的死亡都是由转移性疾病导致的，尽管转移被认为是一个低效的过程。在某些情况下，肿瘤细胞在早期就从原发部位播散，但在很长一段时间内保持惰性，之后才发展成为危及生命的显性肿瘤。对于导致这些惰性肿瘤发展为恶性疾病的机制，我们知之甚少。由于我们在这方面的认知存在差距，所以无法预测哪些乳腺癌患者在原发性肿瘤治疗多年后可能会出现疾病复发或发生转移。更好地理解肿瘤细胞从休眠状态中脱离所涉及的机制和信号，不仅能够更准确地选择可能从全身治疗中获益的患者，还可能会促使开发出更具针对性的疗法，以抑制促进疾病进展 的信号。在这篇综述中，我们探讨了全身或“宏观环境”对肿瘤起始和进展的影响，以及关于促肿瘤性全身环境是如何形成的已知情况。
