Women's Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Women's Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Am J Pathol. 2013 Oct;183(4):1084-1095. doi: 10.1016/j.ajpath.2013.06.012. Epub 2013 Jul 26.
Despite important progress in adjuvant and neoadjuvant therapies, metastatic disease often develops in breast cancer patients and remains the leading cause of their deaths. For patients with established metastatic disease, therapy is palliative, with few breaks and with mounting adverse effects. Many have hypothesized that a personalized or precision approach (the terms are used interchangeably) to cancer therapy, in which treatment is based on the individual characteristics of each patient, will provide better outcomes. Here, we discuss the molecular basis of breast cancer metastasis and the challenges in personalization of treatment. The instability of metastatic tumors remains a leading obstacle to personalization, because information from a patient's primary tumor may not accurately reflect the metastasis, and one metastasis may vary from another. Furthermore, the variable presence of tumor subpopulations, such as stem cells and dormant cells, may increase the complexity of the targeted treatments needed. Although molecular signatures and circulating biomarkers have been identified in breast cancer, there is lack of validated predictive molecular markers to optimize treatment choices for either prevention or treatment of metastatic disease. Finally, to maximize the information that can be obtained, increased attention to clinical trial design in the metastasis preventive setting is needed.
尽管在辅助和新辅助治疗方面取得了重要进展，但转移性疾病仍经常发生在乳腺癌患者中，仍是导致其死亡的主要原因。对于已确诊转移性疾病的患者，治疗是姑息性的，很少有缓解期，且副作用不断增加。许多人假设，对癌症治疗采用个性化或精准治疗方法（这两个术语可互换使用），根据每个患者的个体特征进行治疗，将提供更好的治疗效果。在这里，我们讨论了乳腺癌转移的分子基础以及治疗个性化的挑战。转移性肿瘤的不稳定性仍然是个性化治疗的主要障碍，因为患者原发肿瘤的信息可能无法准确反映转移，而且一个转移灶可能与另一个转移灶不同。此外，肿瘤亚群（如干细胞和休眠细胞）的存在存在差异，这可能会增加靶向治疗的复杂性。尽管已经在乳腺癌中鉴定出了分子特征和循环生物标志物，但缺乏经过验证的预测性分子标志物，无法优化预防或治疗转移性疾病的治疗选择。最后，为了最大限度地获取信息，需要增加对预防转移的临床试验设计的关注。
