PDF(Pubmed)
Abstract：
OBJECTIVE: Although changes in circulating tumour DNA (ctDNA) in breast cancer are well described, the kinetics of their fluctuations has not been described over short timescales. We investigated ctDNA dynamics during alternating cycles of chemotherapy and hormonal treatment in pre-treated patients with oestrogen receptor-positive metastatic breast cancer.
METHODS: Patients received alternating, 9-week cycles of eribulin and aromatase inhibitors (AIs). The clinical primary endpoint, progression-free survival (PFS), was monitored at 3, 6 and 9 months; secondary endpoints, clinical benefit rate (CBR), safety and tolerability profiles, were also assessed. Importantly, ctDNA fluctuations were monitored using the Oncomine™ Breast cfDNA assay to test whether biomarkers may change rapidly between chemotherapy and aromatase inhibitor (AI) treatment in the setting of advanced breast cancer, potentially reflecting disease dynamics.
RESULTS: The median PFS was 202 days (95% CI: 135-undefined) and 235 days (95% CI: 235-undefined) at 6 and 9 months, respectively, with a 50% CBR at both 6 and 9 months. Dynamic changes in ctDNA were observed in short timescales between chemotherapy and AI treatment and support the clinical benefit (CB) seen in individual patients and, critically, appear informative of acquired resistance in real time.
CONCLUSIONS: Changes in ctDNA can occur rapidly and reflect changes in patients\' clinical tumour responses (NCT02681523).
METHODS: Patients received alternating, 9-week cycles of eribulin and aromatase inhibitors (AIs). The clinical primary endpoint, progression-free survival (PFS), was monitored at 3, 6 and 9 months; secondary endpoints, clinical benefit rate (CBR), safety and tolerability profiles, were also assessed. Importantly, ctDNA fluctuations were monitored using the Oncomine™ Breast cfDNA assay to test whether biomarkers may change rapidly between chemotherapy and aromatase inhibitor (AI) treatment in the setting of advanced breast cancer, potentially reflecting disease dynamics.
RESULTS: The median PFS was 202 days (95% CI: 135-undefined) and 235 days (95% CI: 235-undefined) at 6 and 9 months, respectively, with a 50% CBR at both 6 and 9 months. Dynamic changes in ctDNA were observed in short timescales between chemotherapy and AI treatment and support the clinical benefit (CB) seen in individual patients and, critically, appear informative of acquired resistance in real time.
CONCLUSIONS: Changes in ctDNA can occur rapidly and reflect changes in patients\' clinical tumour responses (NCT02681523).
摘要：
目的：尽管乳腺癌中循环肿瘤DNA（ctDNA）的变化已得到很好的描述，其波动的动力学尚未在短时间内描述。我们研究了雌激素受体阳性转移性乳腺癌患者在化疗和激素治疗交替周期期间的ctDNA动力学。
方法：患者接受交替治疗，艾日布林和芳香酶抑制剂（AI）的9周周期。临床主要终点，无进展生存期（PFS），在3、6和9个月进行监测；次要终点，临床获益率（CBR），安全性和耐受性概况，也进行了评估。重要的是,使用Oncomine™BreastcfDNA分析监测ctDNA波动，以测试在晚期乳腺癌背景下，生物标志物是否可能在化疗和芳香化酶抑制剂（AI）治疗之间迅速变化。可能反映疾病动态。
结果：在6个月和9个月时，中位PFS分别为202天（95％CI：135-未定义）和235天（95％CI：235-未定义），分别,在6个月和9个月时都有50%的CBR。在化疗和AI治疗之间的短时间内观察到ctDNA的动态变化，并支持在个体患者中看到的临床益处（CB），至关重要的是，实时显示获得性抵抗力的信息。
结论：ctDNA的变化可以迅速发生并反映患者临床肿瘤反应的变化（NCT02681523）。
方法：患者接受交替治疗，艾日布林和芳香酶抑制剂（AI）的9周周期。临床主要终点，无进展生存期（PFS），在3、6和9个月进行监测；次要终点，临床获益率（CBR），安全性和耐受性概况，也进行了评估。重要的是,使用Oncomine™BreastcfDNA分析监测ctDNA波动，以测试在晚期乳腺癌背景下，生物标志物是否可能在化疗和芳香化酶抑制剂（AI）治疗之间迅速变化。可能反映疾病动态。
结果：在6个月和9个月时，中位PFS分别为202天（95％CI：135-未定义）和235天（95％CI：235-未定义），分别,在6个月和9个月时都有50%的CBR。在化疗和AI治疗之间的短时间内观察到ctDNA的动态变化，并支持在个体患者中看到的临床益处（CB），至关重要的是，实时显示获得性抵抗力的信息。
结论：ctDNA的变化可以迅速发生并反映患者临床肿瘤反应的变化（NCT02681523）。
