Martínez-Sáez Olga, Pascual Tomás, Brasó-Maristany Fara, Chic Nuria, González-Farré Blanca, Sanfeliu Esther, Rodríguez Adela, Martínez Débora, Galván Patricia, Rodríguez Anna Belén, Schettini Francesco, Conte Benedetta, Vidal Maria, Adamo Barbara, Martínez Antoni, Muñoz Montserrat, Moreno Reinaldo, Villagrasa Patricia, Salvador Fernando, Ciruelos Eva M, Faull Iris, Odegaard Justin I, Prat Aleix
SOLTI Cancer Research Group, Barcelona, Spain.
Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain.
NPJ Breast Cancer. 2021 Feb 3;7(1):8. doi: 10.1038/s41523-021-00218-8.
Circulating tumor DNA (ctDNA) levels may predict response to anticancer drugs, including CDK4/6 inhibitors and endocrine therapy combinations (CDK4/6i+ET); however, critical questions remain unanswered such as which assay or statistical method to use. Here, we obtained paired plasma samples at baseline and week 4 in 45 consecutive patients with advanced breast cancer treated with CDK4/6i+ET. ctDNA was detected in 96% of cases using the 74-gene Guardant360 assay. A variant allele fraction ratio (VAFR) was calculated for each of the 79 detected mutations between both timepoints. Mean of all VAFRs (mVAFR) was computed for each patient. In our dataset, mVAFR was significantly associated with progression-free survival (PFS). Baseline VAF, on-treatment VAF or absolute changes in VAF were not associated with PFS, nor were CA-15.3 levels at baseline, week 4 or the CA-15.3 ratio. These findings demonstrate that ctDNA dynamics using a standardized multi-gene panel and a unique methodological approach predicts treatment outcome. Clinical trials in patients with an unfavorable ctDNA response are needed.
循环肿瘤DNA（ctDNA）水平可能预测对抗癌药物的反应，包括细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂和内分泌治疗联合方案（CDK4/6i+ET）；然而，一些关键问题仍未得到解答，比如使用哪种检测方法或统计方法。在此，我们收集了45例接受CDK4/6i+ET治疗的晚期乳腺癌连续患者在基线期和第4周时的配对血浆样本。使用74基因的Guardant360检测法在96%的病例中检测到了ctDNA。计算了两个时间点之间检测到的79个突变各自的变异等位基因分数比（VAFR）。为每位患者计算所有VAFR的平均值（mVAFR）。在我们的数据集中，mVAFR与无进展生存期（PFS）显著相关。基线VAF、治疗期间VAF或VAF的绝对变化均与PFS无关，基线期、第4周时的CA-15.3水平或CA-15.3比值也与PFS无关。这些发现表明，使用标准化多基因检测板和独特方法学途径的ctDNA动态变化可预测治疗结果。需要对ctDNA反应不佳的患者进行临床试验。
