Dawood S, Broglio K, Esteva F J, Ibrahim N K, Kau S-W, Islam R, Aldape K D, Yu T-K, Hortobagyi G N, Gonzalez-Angulo A M
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Medical Oncology, Dubai Hospital, UAE.
Department of Quantitative Sciences.
Ann Oncol. 2008 Jul;19(7):1242-1248. doi: 10.1093/annonc/mdn036. Epub 2008 Mar 11.
The purpose of this retrospective study was to determine, in a cohort of patients with breast cancer and central nervous system (CNS) metastases, the effect of trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive disease and to compare this with that of patients with HER2-negative disease.
Five hundred and ninety-eight patients with invasive breast cancer, CNS metastases and known HER2 status were identified. Time to CNS metastases and survival after CNS metastases were estimated by the Kaplan-Meier method, and Cox models were fitted to determine the association between HER2 status, trastuzumab treatment and outcomes after adjustment for other patient characteristics.
In the multivariable model, patients with HER2-negative disease [Hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.15-1.95, P = 0.003] and patients with HER2-positive disease who did not receive trastuzumab (HR 2.13, 95% CI 1.51-3.00, P < 0.0001) had shorter times to CNS metastases compared with patients with HER2-positive disease who had received trastuzumab as first-line therapy for metastases. Furthermore, patients with HER2-negative disease (HR 1.66, 95% CI 1.31-2.12, P < 0.0001) and patients with HER2-positive disease who had never received trastuzumab (HR 1.34, 95% CI 0.78-2.30, P = 0.28) had an increased hazard of death compared with patients with HER2-positive disease who had received trastuzumab before or at the time of CNS metastases diagnosis.
In our cohort of patients with breast cancer and CNS metastases, patients with HER2-positive disease treated with trastuzumab had longer times to development of and better survival from CNS metastases compared with patients with HER2-positive disease who had never received trastuzumab and patients with HER2-negative breast cancer.
本回顾性研究旨在确定在一组患有乳腺癌和中枢神经系统（CNS）转移的患者中，曲妥珠单抗对人表皮生长因子受体2（HER2）阳性疾病患者的疗效，并将其与HER2阴性疾病患者进行比较。
确定了598例患有浸润性乳腺癌、CNS转移且已知HER2状态的患者。采用Kaplan-Meier方法估计CNS转移时间和CNS转移后的生存期，并拟合Cox模型以确定在调整其他患者特征后HER2状态、曲妥珠单抗治疗与结局之间的关联。
在多变量模型中，与接受曲妥珠单抗作为转移灶一线治疗的HER2阳性疾病患者相比，HER2阴性疾病患者（风险比[HR] 1.50，95%置信区间[CI] 1.15 - 1.95，P = 0.003）和未接受曲妥珠单抗的HER2阳性疾病患者（HR 2.13，95% CI 1.51 - 3.00，P < 0.0001）发生CNS转移的时间更短。此外，与在CNS转移诊断之前或之时接受过曲妥珠单抗治疗的HER2阳性疾病患者相比，HER2阴性疾病患者（HR 1.66，95% CI 1.31 - 2.12，P < 0.0001）和从未接受过曲妥珠单抗治疗的HER2阳性疾病患者（HR 1.34，95% CI 0.78 - 2.30，P = 0.28）死亡风险增加。
在我们这组患有乳腺癌和CNS转移的患者中，与从未接受过曲妥珠单抗治疗的HER2阳性疾病患者及HER2阴性乳腺癌患者相比，接受曲妥珠单抗治疗的HER2阳性疾病患者发生CNS转移的时间更长，且从中枢神经系统转移中存活的时间更长。
