Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.
University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California.
Clin Cancer Res. 2023 Nov 14;29(22):4540-4548. doi: 10.1158/1078-0432.CCR-23-0757.
Breast cancer remains a leading cause of cancer-related death in women despite screening and therapeutic advances. Early detection allows for resection of local disease; however, patients can develop metastatic recurrences years after curative treatment. There is no reliable blood-based monitoring after curative therapy, and radiographic evaluation for metastatic disease is performed only in response to symptoms. Advances in circulating tumor DNA (ctDNA) assays have allowed for a potential option for blood-based monitoring. The detection of ctDNA in the absence of overt metastasis or recurrent disease indicates molecular evidence of cancer, defined as molecular residual disease (MRD). Multiple studies have shown that MRD detection is strongly associated with disease recurrence, with a lead time prior to clinical evidence of recurrence of many months. Importantly, it is still unclear whether treatment changes in response to ctDNA detection will improve outcomes. There are currently ongoing trials evaluating the efficacy of therapy escalation in the setting of MRD, and these studies are being conducted in all major breast cancer subtypes. Additional therapies under study include CDK4/6 inhibitors, PARP inhibitors, HER2-targeted therapies, and immunotherapy. This review will summarize the underlying scientific principles of various MRD assays, their known prognostic roles in early breast cancer, and the ongoing clinical trials assessing the efficacy of therapy escalation in the setting of MRD.
尽管在筛查和治疗方面取得了进展，但乳腺癌仍然是女性癌症相关死亡的主要原因。早期检测可切除局部疾病；然而，患者在根治性治疗后多年仍可发生转移性复发。在根治性治疗后没有可靠的基于血液的监测，并且仅在出现症状时才对转移性疾病进行放射性评估。循环肿瘤 DNA (ctDNA) 检测技术的进步为基于血液的监测提供了一种潜在选择。在没有明显转移或复发疾病的情况下检测到 ctDNA 表明存在癌症的分子证据，定义为分子残留疾病 (MRD)。多项研究表明，MRD 检测与疾病复发强烈相关，其在临床复发证据出现之前有多个月的领先时间。重要的是，目前尚不清楚是否通过 ctDNA 检测来改变治疗方法会改善结果。目前正在进行评估 MRD 情况下治疗升级疗效的临床试验，这些研究正在所有主要乳腺癌亚型中进行。正在研究的其他疗法包括 CDK4/6 抑制剂、PARP 抑制剂、HER2 靶向疗法和免疫疗法。这篇综述将总结各种 MRD 检测的基本科学原理、它们在早期乳腺癌中的已知预后作用，以及正在评估在 MRD 情况下治疗升级疗效的临床试验。
