血浆 HER2ECD 有望成为 HER2 阳性乳腺癌患者预后和预测反应的检测指标：一项随机研究的结果-SAKK 22/99。
Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: results of a randomized study - SAKK 22/99.
机构信息
University Hospital Basel, Institute of Human Genetic and Pathology, Schönbeinstrasse 40, CH-4031, Basel, Switzerland.
SAKK Swiss Group for Clinical Cancer Research Coordinating Centre, Bern, Switzerland.
出版信息
BMC Cancer. 2020 Feb 11;20(1):114. doi: 10.1186/s12885-020-6594-0.
BACKGROUND
The HER2 extracellular domain shed in blood (HER2) is reported to rise and fall in parallel with HER2+ breast cancer behavior. In this study, we evaluated the clinical relevance of plasma HER2 values in patients with metastatic breast cancer treated in the SAKK22/99 trial comparing trastuzumab monotherapy followed by trastuzumab-chemotherapy combination at progression versus upfront combination therapy.
METHODS
Quantitative assessment of plasma HER2 was performed in 133 patients at baseline; after 2-24 h; at 3 weeks; at first response evaluation (8-9 weeks); and at tumor progression. Associations with tumor characteristics, disease course and trial treatment were evaluated.
RESULTS
Baseline HER2 levels were stable within 24 h after the first trastuzumab injection. These plasma values correlated positively with the HER2 gene ratio (r = 0.39, P < 0.001) and HER2 protein expression levels (r = 0.36, P < 0.001) but not with ER/PR status of the primary tumor. HER2 baseline levels were positively associated with the presence of visceral disease (P = 0.05) and poor patients' outcome (Cox-regression: P = 0.009). Patients with high baseline levels (> 35 ng/ml) had the worst overall survival (P = 0.03) if treated with upfront combination therapy. Conversely, patients with low HER2 baseline values (< 15 ng/ml) had longer time to progression on combined trastuzumab-chemotherapy when first treated with trastuzumab monotherapy (P = 0.02). Monitoring HER2 levels during the course of the trial revealed significant time (P = 0.001) and time-treatment arm interactions (P = 0.0007). Under upfront trastuzumab alone, the HER2 levels remained stable until just before disease progression. In patients responding to combination treatment HER2 levels decreased to > 20%.
CONCLUSIONS
Plasma HER2 levels in patients with metastatic breast cancer reflect HER2 disease status. This robust biomarker might help identifying patients without visceral disease profiting from a sequential treatment's modality. Monitoring HER2 levels during trastuzumab monotherapy could help defining the optimal time to introduce chemotherapy.
TRIAL REGISTRATION
Registration Number by ClinicalTrials.gov: NCT00004935, Trial number: SAKK22/99. Registered on 27 January 2003.
背景
据报道，血液中 HER2 细胞外结构域（HER2）的升高和降低与 HER2+乳腺癌的行为呈平行关系。在这项研究中，我们评估了 SAKK22/99 试验中转移性乳腺癌患者血浆 HER2 值的临床相关性，该试验比较了曲妥珠单抗单药治疗后进展时的曲妥珠单抗-化疗联合治疗与起始时的联合治疗。
方法
对 133 例患者在基线时、2-24 小时后、3 周时、首次反应评估（8-9 周）时和肿瘤进展时进行血浆 HER2 的定量评估。评估了与肿瘤特征、疾病过程和试验治疗的相关性。
结果
首次曲妥珠单抗注射后 24 小时内，基线 HER2 水平稳定。这些血浆值与 HER2 基因比值呈正相关（r=0.39，P<0.001），与 HER2 蛋白表达水平呈正相关（r=0.36，P<0.001），但与原发性肿瘤的 ER/PR 状态无关。基线 HER2 水平与内脏疾病的存在呈正相关（P=0.05），与患者预后不良呈正相关（Cox 回归：P=0.009）。基线水平较高（>35ng/ml）的患者如果接受起始联合治疗，总体生存率最差（P=0.03）。相反，基线 HER2 值较低（<15ng/ml）的患者如果首先接受曲妥珠单抗单药治疗，然后再接受曲妥珠单抗联合化疗，进展时间更长（P=0.02）。在试验过程中监测 HER2 水平显示出显著的时间（P=0.001）和时间-治疗臂相互作用（P=0.0007）。在单独使用曲妥珠单抗的起始阶段，HER2 水平保持稳定，直到疾病进展前。在对联合治疗有反应的患者中，HER2 水平下降至>20%。
结论
转移性乳腺癌患者的血浆 HER2 水平反映了 HER2 疾病状态。这种强大的生物标志物可能有助于识别没有内脏疾病的患者，他们从序贯治疗模式中获益。在曲妥珠单抗单药治疗期间监测 HER2 水平可能有助于确定引入化疗的最佳时间。
临床试验注册
ClinicalTrials.gov 注册号：NCT00004935，试验编号：SAKK22/99。于 2003 年 1 月 27 日注册。
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