Kinetics and determinants of ESR1 mutation detection in metastatic breast cancer.

Here, we describe the kinetics and determinants of bESR1-mut in the 1017 patients who participated in PADA-1.

在这里，我们描述了在参与PADA-1的1017名患者中，bESR1-mut的动力学和决定因素。

patients_and_methods

PADA-1 was an open-label, randomized, controlled, phase III trial conducted at 83 hospitals in France.

PADA-1 是在法国 83 家医院进行的一项开放标签、随机对照、III 期临床试验。

Patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer were recruited and monitored by multiplex droplet digital PCR for rising bESR1-mut during first-line treatment with aromatase inhibitor and palbociclib, after one cycle and then every two cycles.

该试验招募了激素受体阳性/人类表皮生长因子受体2阴性的晚期乳腺癌患者，并通过多重液滴数字PCR监测在芳香酶抑制剂和帕博西利一线治疗期间bESR1突变的上升，首次治疗后一个周期以及之后每两个周期进行一次监测。

Patients with newly present or increased bESR1-mut in circulating tumor DNA and no synchronous disease progression were randomly assigned to continue with the same therapy or to switch to fulvestrant and palbociclib.

新出现或循环肿瘤DNA中bESR1突变增加的患者，且无同时性疾病进展，被随机分配继续接受相同治疗或改用fulvestrant和palbociclib。

Results

Baseline bESR1-mut was detected in 3.2% of patients.

基线时在3.2%的患者中检测到bESR1突变。

Prior adjuvant treatment with aromatase inhibitor (6.8%) and lower body mass index were independently associated with a higher detection rate of bESR1-mut at baseline.

先前使用芳香酶抑制剂的辅助治疗（6.8%）和较低的身体质量指数（BMI）与基线时bESR1突变的较高检出率独立相关。

Through real-time analysis of >12 500 blood samples, we observed that detection of rising bESR1-mut was not linear over time, occurring more frequently after 6 months and before 3 years of treatment.

通过对超过12,500个血液样本进行实时分析，我们观察到bESR1突变的检出率随时间增长并非线性，在治疗6个月后和3年之前更为频繁。

We found that high estrogen receptor expression, the presence of bone metastases, younger age, and lactate dehydrogenase elevation were associated with a higher rate of rising bESR1-mut detection.

我们发现，高雌激素受体表达、骨转移的存在、年轻年龄和乳酸脱氢酶升高与bESR1突变检出率上升有关。

Finally, updated survival results of PADA-1 substantiate the clinical benefit of intercepting bESR1-mut emergence before clinical progression, with improved progression-free survival(PFS), hazard ratio0.54, 95% confidence interval0.38-0.75, and progression-free survival2, hazard ratio0.35, 95% confidence interval0.22-0.54.

最后，PADA-1的最新生存结果证实，在临床进展之前拦截bESR1突变出现的临床益处，改善了无进展生存期（PFS），风险比为0.54，95%置信区间为0.38-0.75，以及无进展生存期2，风险比为0.35，95%置信区间为0.22-0.54。

Conclusions

We identified factors associated with the detection of bESR1-mut at baseline and during treatment that could help identify patients who may benefit from ESR1-targeted therapies.

我们确定了与基线和治疗期间检测到bESR1突变相关的因素，这可能有助于识别可能从ESR1靶向治疗中受益的患者。