Swedish Cancer Institute, Seattle, Washington, USA.
Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, Illinois, USA.
Oncologist. 2020 May;25(5):391-397. doi: 10.1634/theoncologist.2019-0099. Epub 2020 Feb 19.
In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stimulating factor (G-CSF), but not pegylated G-CSF, has been identified as a factor associated with increased t-MDS/AML risk. Two newly identified associations may link homologous DNA repair gene deficiency and poly (ADP-ribose) polymerase inhibitor treatment to increased t-MDS/AML risk. When predisposing factors, such as young age, are combined with an increasing number of potentially leukemogenic treatments that may not confer large risk singly, the risk of t-MDS/AML appears to increase. Patient and treatment factors combine to form a biological cascade that can trigger a myelodysplastic event. Patients with breast cancer are often exposed to many of these risk factors in the course of their treatment, and triple-negative patients, who are often younger and/or BRCA positive, are often exposed to all of them. It is important going forward to identify effective therapies without these adverse associated effects and choose existing therapies that minimize the risk of t-MDS/AML without sacrificing therapeutic gain. IMPLICATIONS FOR PRACTICE: Breast cancer is far more curable than in the past but requires multimodality treatment. Great care must be taken to use the least leukemogenic treatment programs that do not sacrifice efficacy. Elimination of radiation and anthracycline/alkylating agent regimens will be helpful where possible, particularly in younger patients and possibly those with homologous repair deficiency (HRD). Use of colony-stimulating factors should be limited to those who truly require them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed.
在这篇综述中，我们总结了各种乳腺癌治疗方式以及固有患者因素对治疗后骨髓增生异常综合征和急性髓系白血病（t-MDS/AML）发生的影响。显然，年龄较小的患者接受放疗和化疗的风险增加。放疗相关风险适中，而化疗，尤其是烷化剂和蒽环类药物的联合治疗，风险更高，放疗和化疗联合使用会显著增加风险。最近，粒细胞集落刺激因子（G-CSF）的治疗，而不是聚乙二醇化 G-CSF 的治疗，被确定为与增加 t-MDS/AML 风险相关的一个因素。最近发现的两个新关联可能将同源 DNA 修复基因缺陷和多聚（ADP-核糖）聚合酶抑制剂治疗与增加 t-MDS/AML 风险联系起来。当存在易患因素（如年龄较小）时，与可能不会单独产生较大风险的越来越多的潜在致白血病治疗相结合，t-MDS/AML 的风险似乎会增加。患者和治疗因素结合形成一个生物学级联，可以触发骨髓增生异常事件。乳腺癌患者在治疗过程中经常接触到许多这些危险因素，而三阴性患者，通常年龄较小且/或 BRCA 阳性，经常接触到所有这些因素。重要的是要在未来找到没有这些不良相关作用的有效治疗方法，并选择在不牺牲治疗效果的情况下将 t-MDS/AML 风险最小化的现有治疗方法。
乳腺癌的治疗效果比过去要好得多，但需要采用多模式治疗。在使用不会牺牲疗效的最少致白血病治疗方案时，必须格外小心。在可能的情况下，特别是在年轻患者和可能具有同源修复缺陷（HRD）的患者中，消除放疗和蒽环类药物/烷化剂方案将有所帮助。对于需要安全化疗管理的患者，应将集落刺激因子的使用限制在真正需要的患者。迫切需要进一步研究 HRD 和各种形式的集落刺激因子与可能的致白血病关联。
