Translational Cancer Research Branch, Research Institute, National Cancer Center, Goyang, Republic of Korea.
Center for Breast Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Republic of Korea.
Sci Rep. 2021 Mar 10;11(1):5566. doi: 10.1038/s41598-021-84999-9.
We prospectively evaluated the utility of ESR1 and PIK3CA mutation analysis with cell-free DNA (cfDNA) using droplet digital PCR (ddPCR) for the efficacy of endocrine therapy (ET) in hormone receptive positive (HR+) metastatic breast cancer (MBC) patients. CfDNA was analyzed just before the start of ET for MBC. E380Q, Y537N, Y537S, and D538G were assessed for ESR1 mutations and H1047R, E545K, and E542K were assessed for PIK3CA mutations. A total of 75 patients were enrolled. Of those, 31 (41.3%) received letrozole with palbociclib, and 28 (37.3%) received exemestane and everolimus (EverX). ESR1 mutations were found in 36 (48.0%) patients, of which 16 (21.3%) had more than one variant. Seventeen (23.6%) patients had one PIK3CA mutation and 8 (11.1%) had two. In the total population, time to progression of the first ET after enrollment (TTP1) decreased significantly as the number of ESR1 mutations increased (p < 0.001). PIK3CA mutations were also significantly associated with shorter TTP1 (median TTP1: 16.2 months vs. 10.9 months, p = 0.03). In contrast, PIK3CA mutations were significantly associated with longer TTP in patients receiving EverX treatment (median TTP of EverX: 15.9 months vs. 5.2 months, p = 0.01) and remained a significant factor in multivariable analysis for TTP of EverX in this subgroup (hazard ratio = 0.2, 95% CI = 0.1- 0.8, p = 0.03). ESR1 and PIK3CA mutations in cfDNA were associated with clinical efficacies of ET in HR+ MBC patients.
我们前瞻性地评估了使用液滴数字 PCR（ddPCR）检测游离 DNA（cfDNA）中的 ESR1 和 PIK3CA 突变分析在激素受体阳性（HR+）转移性乳腺癌（MBC）患者内分泌治疗（ET）中的疗效。在开始 MBC 的 ET 之前，对 cfDNA 进行了分析。评估了 E380Q、Y537N、Y537S 和 D538G 处的 ESR1 突变，以及 H1047R、E545K 和 E542K 处的 PIK3CA 突变。共纳入 75 例患者。其中 31 例（41.3%）接受来曲唑联合 palbociclib，28 例（37.3%）接受依西美坦和 everolimus（EverX）。在 36 例（48.0%）患者中发现了 ESR1 突变，其中 16 例（21.3%）有不止一种变异。17 例（23.6%）患者有一种 PIK3CA 突变，8 例（11.1%）有两种。在总人群中，随着 ESR1 突变数量的增加，首次 ET 后的进展时间（TTP1）显著降低（p<0.001）。PIK3CA 突变也与较短的 TTP1 显著相关（中位 TTP1：16.2 个月 vs. 10.9 个月，p=0.03）。相比之下，PIK3CA 突变与接受 EverX 治疗的患者的更长 TTP 相关（EverX 的中位 TTP：15.9 个月 vs. 5.2 个月，p=0.01），并且在该亚组的 EverX 治疗 TTP 的多变量分析中仍然是一个显著因素（风险比=0.2，95%CI=0.1-0.8，p=0.03）。cfDNA 中的 ESR1 和 PIK3CA 突变与 HR+MBC 患者 ET 的临床疗效相关。
