Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY, USA.
Mount Sinai Beth Israel Comprehensive Cancer Center, New York, NY, USA.
Breast Cancer Res Treat. 2020 Jul;182(2):381-388. doi: 10.1007/s10549-020-05712-4. Epub 2020 May 30.
Skeletal-related events (SREs) are significant contributors to the morbidity and mortality in patients with bone metastasis from breast cancer. Thus, bone-modifying agents (BMAs) are recommended in this population. However, the baseline risk factors of SREs in patients with bone metastasis from breast cancer receiving BMAs are not well understood.
We analyzed the patient-level data from a controlled arm of a clinical trial comparing denosumab with zoledronate in patients with bone metastases from breast cancer (ClinicalTrial.gov ID: NCT00321464) available at Project Data Sphere, a broad-access research platform that collects and curates patient-level data from completed, phase III cancer trials. The primary endpoint was the first SRE after the inclusion to the trial. The time to the first on study SRE was analyzed using Cox proportional hazards model based on patients' baseline characteristics including age, race, ECOG performance status (PS), histology and immunohistochemistry of breast cancer, and urine and serum laboratory data.
Among 756 patients in the zoledronate arm of the trial, we excluded 64 patients with a documented history of osteopenia or osteoporosis. The median age of the patients was 56 years old, the median follow-up was 553 days, and 249 patients (36%) had SREs. The univariate analysis showed that black or African American heritage, ECOG PS > 0, human epidermal growth factor receptor 2 (HER2) positivity, high urine N-telopeptide cross-links / creatinine ratio (NTx/Cre), and elevated serum alkaline phosphatase (ALP) are significant baseline risk factors for SREs. Patients with the characteristics of ECOG PS > 0, HER2 positivity, and elevated ALP also showed a significantly higher hazard ratio of SREs in multivariate analysis.
We determined risk factors for SREs in patients with bone metastasis from breast cancer.
骨骼相关事件（SREs）是乳腺癌骨转移患者发病率和死亡率的重要因素。因此，建议在该人群中使用骨修饰剂（BMA）。然而，接受 BMA 的乳腺癌骨转移患者 SREs 的基线风险因素尚不清楚。
我们分析了来自临床试验的对照臂的患者水平数据，该临床试验比较了地舒单抗与唑来膦酸在乳腺癌骨转移患者中的疗效（ClinicalTrial.gov ID：NCT00321464），这些数据可在 Project Data Sphere 上获得，这是一个广泛获取的研究平台，从已完成的 III 期癌症试验中收集和整理患者水平数据。主要终点是纳入试验后的首次 SRE。首次研究 SRE 的时间使用基于患者基线特征的 Cox 比例风险模型进行分析，这些特征包括年龄、种族、ECOG 表现状态（PS）、乳腺癌的组织学和免疫组织化学以及尿液和血清实验室数据。
在试验的唑来膦酸组的 756 名患者中，我们排除了 64 名有骨质疏松或骨质疏松症病史的患者。患者的中位年龄为 56 岁，中位随访时间为 553 天，有 249 名患者（36%）发生了 SREs。单因素分析显示，黑种人或非裔美国人、ECOG PS>0、人表皮生长因子受体 2（HER2）阳性、高尿 N-末端肽交联/肌酐比（NTx/Cre）和碱性磷酸酶（ALP）升高是 SREs 的显著基线风险因素。在多因素分析中，ECOG PS>0、HER2 阳性和 ALP 升高的患者发生 SREs 的风险比也显著更高。
我们确定了乳腺癌骨转移患者 SREs 的风险因素。
