曲妥珠单抗治疗 HER2 阳性转移性乳腺癌患者生存的影响因素。
Factors influencing survival among patients with HER2-positive metastatic breast cancer treated with trastuzumab.
机构信息
Division of Medical Oncology, London Regional Cancer Program, University of Western Ontario, London, ON, N6H 4L6, Canada.
Institute of Health Policy, Evaluation and Management, University of Toronto, Toronto, ON, Canada.
出版信息
Breast Cancer Res Treat. 2018 Jul;170(1):169-177. doi: 10.1007/s10549-018-4734-x. Epub 2018 Mar 8.
PURPOSE
We have limited capability to predict survival among patients treated for metastatic HER2-positive breast cancer. Further research is warranted to identify significant prognostic and predictive factors.
METHODS
We identified all HER2-positive metastatic breast cancer patients receiving trastuzumab at the Sunnybrook Odette Cancer Centre (SOCC) from 1999 to 2013 through the Cancer Care Ontario (CCO) Registry (n = 256) and selected patients with available pathology reports (n = 154). A retrospective review was completed documenting clinical, pathologic, and laboratory characteristics at the time of first trastuzumab therapy and survival outcomes. Cox proportional hazards regression models were used to identify prognostic factors for overall survival (OS) (primary endpoint) and failure-free survival (FFS), adjusted for the known prognostic factors of the presence of CNS metastases and the presence of ≥ 2 distant metastatic sites.
RESULTS
A multivariable model identified older age [hazard ratio (HR) 1.18/decade, 95% confidence interval (CI) 1.02-1.37)], increased platelet-to-lymphocyte ratio (PLR) (HR 1.75/log-unit, 95% CI 1.25-2.46), increased serum alkaline phosphatase (ALP) (HR 1.87/log-unit, 95% CI 1.41-2.49), and ER positivity (HR 0.63, 95% CI 0.42-0.96) as significant prognostic factors for OS after adjusting for the presence of CNS metastasis (HR 3.19, 95% CI 1.59-6.38) and the presence of ≥ 2 distant metastatic sites (HR 2.10, 95% CI 1.19-3.70). PLR (HR 1.54/log-unit, 95% CI 1.12-2.12) was the only prognostic factor associated with FFS after adjusting for CNS and ≥ 2 distant metastatic sites.
CONCLUSION
Older age, increased PLR, and ALP were identified as poor prognostic factors and ER positivity as a favorable prognostic factor for OS after adjusting for the presence of CNS metastasis and the presence of number of ≥ 2 distant metastatic sites. Increased PLR was a poor prognostic factor for both OS and FFS, and warrants further investigation into its prognostic ability amongst patients with HER2-positive metastatic breast cancer.
目的
我们预测接受曲妥珠单抗治疗的转移性人表皮生长因子受体 2（HER2）阳性乳腺癌患者生存情况的能力有限。有必要进一步研究以确定显著的预后和预测因素。
方法
通过安大略省癌症护理（CCO）登记处（n=256），我们确定了 1999 年至 2013 年期间在 Sunnybrook Odette 癌症中心（SOCC）接受曲妥珠单抗治疗的所有 HER2 阳性转移性乳腺癌患者，并选择了具有可用病理报告的患者（n=154）。通过回顾性审查记录了首次接受曲妥珠单抗治疗时的临床、病理和实验室特征以及生存结果。使用 Cox 比例风险回归模型，根据中枢神经系统转移的存在和≥2 个远处转移部位的存在这两个已知的预后因素，识别总生存（OS）（主要终点）和无失败生存（FFS）的预后因素。
结果
多变量模型确定了年龄较大（风险比[HR]每 10 年增加 1.18，95%置信区间[CI]为 1.02-1.37）、血小板与淋巴细胞比值（PLR）升高（HR 1.75/log 单位，95%CI 为 1.25-2.46）、血清碱性磷酸酶（ALP）升高（HR 1.87/log 单位，95%CI 为 1.41-2.49）和 ER 阳性（HR 0.63，95%CI 为 0.42-0.96）是 OS 的显著预后因素，在调整了中枢神经系统转移（HR 3.19，95%CI 为 1.59-6.38）和≥2 个远处转移部位（HR 2.10，95%CI 为 1.19-3.70）的存在后。PLR（HR 1.54/log 单位，95%CI 为 1.12-2.12）是调整 CNS 和≥2 个远处转移部位后唯一与 FFS 相关的预后因素。
结论
在调整中枢神经系统转移和≥2 个远处转移部位的存在后，年龄较大、PLR 和 ALP 被确定为预后不良的因素，ER 阳性为 OS 的有利预后因素。PLR 是 OS 和 FFS 的不良预后因素，需要进一步研究其在 HER2 阳性转移性乳腺癌患者中的预后能力。
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