Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Human Oncology and Pathogenesis Program and Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY.
J Natl Cancer Inst. 2020 Jan 1;112(1):107-110. doi: 10.1093/jnci/djz157.
Chemotherapy and radiation therapy are the foundations of adjuvant therapy for early-stage breast cancer. As a complication of cytotoxic regimens, breast cancer patients are at risk for therapy-related myeloid neoplasms (t-MNs). These t-MNs are commonly refractory to antileukemic therapies and result in poor patient outcomes. We previously demonstrated that somatic mutations in leukemia-related genes are present in the tumor-infiltrating leukocytes (TILeuks) of a subset of early breast cancers. Here, we performed genomic analysis of microdissected breast cancer tumor cells and TILeuks from seven breast cancer patients who subsequently developed leukemia. In four patients, mutations present in the leukemia were detected in breast cancer TILeuks. This finding suggests that TILeuks in the primary breast cancer may harbor the ancestor of the future leukemogenic clone. Additional research is warranted to ascertain whether infiltrating mutant TILeuks could constitute a biomarker for the development of t-MN and to determine the functional consequences of mutant TILeuks.
化疗和放疗是早期乳腺癌辅助治疗的基础。作为细胞毒性治疗方案的并发症，乳腺癌患者有发生治疗相关髓系肿瘤（t-MN）的风险。这些 t-MN 通常对白血病治疗药物具有抗药性，导致患者预后不良。我们之前的研究表明，某些早期乳腺癌的肿瘤浸润白细胞（TILeuks）中存在与白血病相关的基因的体细胞突变。在这里，我们对随后发生白血病的七名乳腺癌患者的微切割乳腺癌肿瘤细胞和 TILeuks 进行了基因组分析。在四名患者中，在白血病中发现的突变也存在于乳腺癌 TILeuks 中。这一发现表明，原发性乳腺癌中的 TILeuks 可能携带着未来白血病克隆的祖先。需要进一步的研究来确定浸润性突变 TILeuks 是否可以作为 t-MN 发生的生物标志物，并确定突变 TILeuks 的功能后果。
