Jongbloed Elisabeth M, Deger Teoman, Sleijfer Stefan, Martens John W M, Jager Agnes, Wilting Saskia M
Department of Medical Oncology, Erasmus University MC Cancer Institute, Dr. Molewaterplein 40, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Cancers (Basel). 2021 Apr 10;13(8):1811. doi: 10.3390/cancers13081811.
Monitoring treatment response in metastatic breast cancer currently consists mainly of radiological and clinical assessments. These methods have high inter-observer variation, suboptimal sensitivity to determine response to treatment and give little insight into the biological characteristics of the tumor. Assessing circulating tumor DNA (ctDNA) over time could be employed to address these limitations. Several ways to quantify and characterize ctDNA exist, based on somatic mutations, copy number variations, methylation, and global circulating cell-free DNA (cfDNA) fragment sizes and concentrations. These methods are being explored and technically validated, but to date none of these methods are applied clinically. We systematically reviewed the literature on the use of quantitative ctDNA measurements over time to monitor response to systemic therapy in patients with metastatic breast cancer. Cochrane, Embase, PubMed and Google Scholar databases were searched to find studies focusing on the use of cfDNA to longitudinally monitor treatment response in advanced breast cancer patients until October 2020. This resulted in a total of 33 studies which met the inclusion criteria. These studies were heterogeneous in (pre-)processing procedures, applied techniques and design. An association between ctDNA and treatment response was found in most of the included studies, independent of the applied assay. To implement ctDNA-based response monitoring into daily clinical practice for metastatic breast cancer patients, sample (pre-) processing procedures need to be standardized and large prospectively collected sample cohorts with well annotated clinical follow-up are required to establish its clinical validity.
目前，转移性乳腺癌治疗反应的监测主要包括影像学和临床评估。这些方法存在较高的观察者间差异，对治疗反应的判定敏感性欠佳，且对肿瘤生物学特征的洞察有限。评估循环肿瘤DNA（ctDNA）随时间的变化可用于解决这些局限性。基于体细胞突变、拷贝数变异、甲基化以及整体循环游离DNA（cfDNA）片段大小和浓度，存在多种量化和表征ctDNA的方法。这些方法正在探索和进行技术验证，但迄今为止，这些方法均未应用于临床。我们系统回顾了关于使用随时间定量ctDNA测量来监测转移性乳腺癌患者全身治疗反应的文献。检索了Cochrane、Embase、PubMed和谷歌学术数据库，以查找截至2020年10月关注使用cfDNA纵向监测晚期乳腺癌患者治疗反应的研究。共得到33项符合纳入标准的研究。这些研究在（预）处理程序、应用技术和设计方面存在异质性。在大多数纳入研究中均发现ctDNA与治疗反应之间存在关联，与所应用的检测方法无关。为了将基于ctDNA的反应监测应用于转移性乳腺癌患者的日常临床实践，样本（预）处理程序需要标准化，并且需要大量前瞻性收集的样本队列以及详细注释的临床随访来确定其临床有效性。
