一线抗芳香化酶治疗转移性乳腺癌时，根据循环 ESR1 突变、CA-15.3 和 cfDNA 早期进展的风险增加。
Risk of early progression according to circulating ESR1 mutation, CA-15.3 and cfDNA increases under first-line anti-aromatase treatment in metastatic breast cancer.
机构信息
Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
Normandie Univ, UNIROUEN, Inserm U1245, IRON group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.
出版信息
Breast Cancer Res. 2020 May 28;22(1):56. doi: 10.1186/s13058-020-01290-x.
BACKGROUND
Endocrine therapy is recommended as a first-line treatment for hormone receptor-positive metastatic breast cancer (HR+MBC) patients. No biomarker has been validated to predict tumor progression in that setting. We aimed to prospectively compare the risk of early progression according to circulating ESR1 mutations, CA-15.3, and circulating cell-free DNA in MBC patients treated with a first-line aromatase inhibitor (AI).
METHODS
Patients with MBC treated with a first-line AI were prospectively included. Circulating biomarker assessment was performed every 3 months. The primary objective was to determine the risk of progression or death at the next follow-up visit (after 3 months) in case of circulating ESR1 mutation detection among patients treated with a first-line AI for HR+MBC.
RESULTS
Overall, 103 patients were included, and 70 (68%) had progressive disease (PD). Circulating ESR1 mutations were detected in 22/70 patients with PD and in 0/33 patients without progression (p < 0.001). Among the ESR1-mutated patients, 18/22 had a detectable mutation prior to progression, with a median delay of 110 days from first detection to PD. The detection of circulating ESR1 mutations was associated with a 4.9-fold (95% CI 3.0-8.0) increase in the risk of PD at 3 months. Using a threshold value of 25% or 100%, a CA-15.3 increase was also correlated with progression (p < 0.001 and p = 0.003, respectively). In contrast to ESR1, the CA-15.3 increase occurred concomitantly with PD in most cases, in 27/47 (57%) with a 25% threshold and in 21/25 (84%) with a 100% threshold. Using a threshold value of either 25% or 100%, cfDNA increase was not correlated with progression.
CONCLUSION
The emergence of circulating ESR1 mutations is associated with a 4.9-fold increase in the risk of early PD during AI treatment in HR+MBC. Our results also highlighted that tracking circulating ESR1 mutations is more relevant than tracking CA-15.3 or cfDNA increase to predict progression in this setting.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT02473120. Registered 16 June 2015-retrospectively registered after one inclusion (first inclusion 1 June 2015).
背景
内分泌治疗被推荐作为激素受体阳性转移性乳腺癌（HR+MBC）患者的一线治疗方法。目前尚无生物标志物可用于预测该治疗环境下的肿瘤进展。我们旨在前瞻性比较循环 ESR1 突变、CA-15.3 和循环游离 DNA 在接受一线芳香酶抑制剂（AI）治疗的 MBC 患者中的早期进展风险。
方法
前瞻性纳入接受一线 AI 治疗的 MBC 患者。每 3 个月进行一次循环生物标志物评估。主要目的是确定在 HR+MBC 患者接受一线 AI 治疗后，如果检测到循环 ESR1 突变，在下一次随访（3 个月后）时进展或死亡的风险。
结果
共纳入 103 例患者，其中 70 例（68%）发生疾病进展（PD）。在 70 例 PD 患者中有 22 例检测到循环 ESR1 突变，而在 33 例无进展患者中无 1 例检测到（p<0.001）。在 ESR1 突变患者中，18/22 例在进展前可检测到突变，从首次检测到 PD 的中位延迟为 110 天。循环 ESR1 突变的检测与 3 个月时 PD 的风险增加 4.9 倍（95%CI 3.0-8.0）相关。使用 25%或 100%的阈值，CA-15.3 的增加也与进展相关（p<0.001 和 p=0.003）。与 ESR1 不同，CA-15.3 的增加在大多数情况下与 PD 同时发生，在 25%阈值时有 27/47 例（57%），在 100%阈值时有 21/25 例（84%）。使用 25%或 100%的阈值，cfDNA 的增加与进展无关。
结论
在 HR+MBC 中，接受 AI 治疗期间，循环 ESR1 突变的出现与早期 PD 风险增加 4.9 倍相关。我们的结果还强调，与跟踪 CA-15.3 或 cfDNA 增加相比，跟踪循环 ESR1 突变更能预测该环境下的进展。
试验注册
ClinicalTrials.gov，NCT02473120。2015 年 6 月 16 日注册-2015 年 6 月 1 日纳入后进行回顾性注册（首次纳入日期为 2015 年 6 月 1 日）。
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