Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Danish Breast Cancer Group, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Acta Oncol. 2023 Jun;62(6):601-607. doi: 10.1080/0284186X.2023.2224926. Epub 2023 Jun 20.
The purpose was to investigate the treatment flow of patients with HER2-positive metastatic breast cancer (mBC), progression-free survival (PFS) and overall survival (OS) across treatment lines and adherence to guidelines (defined as trastuzumab, pertuzumab and chemotherapy first line, where 85% received vinorelbine as backbone and T-DM1 second line). Furthermore, we identified clinical markers to predict the risk of developing brain metastases.
Patients with HER2-positive mBC, diagnosed between 01.01.2014-31.12.2019, registered in the database of the Danish Breast Cancer Group were included in this real-word study. Clinical follow-up was assessed until 01.10.2020 and complete follow-up for overall survival until 01.10.2021. Survival data were analyzed using the Kaplan-Meier method with guidelines adherence analyzed as a time-varying covariate, and the risk of CNS metastasis was estimated by the cumulative incidence function.
631 patients were included. 329 (52%) patients followed the guidelines. The median OS for all patients was 42.3 months (95% Cl, 38.2-48.4), and significantly higher for the patients who followed guidelines; NA (95% CI, 78.2-NA). The median PFS for all patients was 13.4 months (95% Cl, 12.1-14.8), 6.6 (95% Cl, 5.8-7.6) and 5.8 (95% Cl, 4.9-6.9) for first, second and third line of treatment, respectively. Patients with ER-negative mBC had a higher risk of developing brain metastases and patients with high tumor burden had a higher risk of developing brain metastases with an adjusted HR of 0.69 (95% CI, 0.49-0.98), = 0.047 and 2.69 (95% CI, 1.45-5.00), = 0.002, respectively.
We found that only half of the patients with HER2-positive mBC, received first and second-line treatment according to national guidelines. Patients receiving treatment according to guidelines had a significantly higher median OS compared to patients who did not. We also found that patients with ER-negative disease or high tumor burden had a significantly higher risk of developing brain metastases.
本研究旨在调查曲妥珠单抗、帕妥珠单抗和化疗一线治疗（其中 85%患者接受长春瑞滨作为骨干药物，T-DM1 二线治疗），以及 HER2 阳性转移性乳腺癌（mBC）患者的治疗流程、无进展生存期（PFS）和总生存期（OS）随治疗线数的变化情况，并评估其对指南的遵循情况。此外，我们还确定了预测发生脑转移风险的临床标志物。
本回顾性研究纳入了 2014 年 1 月 1 日至 2019 年 12 月 31 日期间在丹麦乳腺癌协作组数据库中登记的 HER2 阳性 mBC 患者。临床随访截止至 2020 年 10 月 1 日，总生存随访截止至 2021 年 10 月 1 日。采用 Kaplan-Meier 法分析生存数据，并将指南遵循情况作为时变协变量进行分析，采用累积发病率函数估计中枢神经系统转移风险。
共纳入 631 例患者，其中 329 例（52%）患者遵循了指南。所有患者的中位 OS 为 42.3 个月（95%CI，38.2-48.4），遵循指南的患者 OS 显著更高（中位 OS：NA，95%CI，78.2-NA）。所有患者的中位 PFS 为 13.4 个月（95%CI，12.1-14.8），一线、二线和三线治疗的中位 PFS 分别为 6.6（95%CI，5.8-7.6）、5.8（95%CI，4.9-6.9）和 5.8（95%CI，4.9-6.9）。ER 阴性 mBC 患者发生脑转移的风险更高，肿瘤负荷高的患者发生脑转移的风险也更高，校正 HR 分别为 0.69（95%CI，0.49-0.98）、=0.047 和 2.69（95%CI，1.45-5.00）、=0.002。
我们发现，只有一半的 HER2 阳性 mBC 患者接受了符合国家指南的一线和二线治疗。与未遵循指南的患者相比，遵循指南的患者中位 OS 显著更高。我们还发现，ER 阴性疾病或肿瘤负荷高的患者发生脑转移的风险显著更高。
