浸润性乳腺癌早期骨转移的预后影响因素分析

Analysis of prognostic factors for early bone metastasis of invasive breast cancer

目的 :研究骨唾液酸蛋白(bone sialoprotein,BSP)、人表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)、雌激素受体(estrogen receptor,ER)/孕激素受体(progesterone receptor,PR)和Ki-67等临床病理学指标与浸润性乳腺癌早期骨转移的关系,分析乳腺癌术后3年无骨转移生存(bone metastasisfree survival,BMFS)的预后影响因素。方法 :收集河北医科大学第四医院肿瘤内科2009年1月1日—2009年12月31日收治的171例女性浸润性乳腺癌患者的术后乳腺癌组织石蜡标本,应用免疫组织化学SP法检测BSP、HER-2、ER、PR和Ki-67的表达水平。收集所有患者的临床病理学资料。根据术后随访结果,将患者分为骨转移组与无骨转移组。应用3年BMFS作为早期骨转移评价指标。采用χ2检验分析两组患者临床病理学特征的差异,Kaplan-Meier单因素分析与3年BMFS相关的因素,log-rank检验进行3年BMFS的比较,COX比例风险模型分析与3年BMFS相关的独立预后因素。结果 :骨转移组的BSP阳性表达率(67.4%)显著高于无骨转移组(44.3%,P=0.002);BSP的表达与年龄、肿瘤直径、转移淋巴结数目、术后TNM分期、ER、PR、HER-2、Ki-67和病理类型均无明显相关性(P>0.05)。单因素分析显示,BSP阳性患者的3年BMFS(47.42%)显著低于BSP阴性患者(68.92%,P=0.001),肿瘤直径>3 cm的患者(49.15%)显著低于肿瘤直径≤3 cm的患者(62.50%,P=0.014);ER阳性患者(63.56%)显著高于ER阴性患者(41.51%,P=0.027)。COX比例风险模型分析结果显示,BSP阳性(风险比为2.179,P=0.000)和肿瘤直径>3 cm(风险比为1.580,P=0.011)是乳腺癌术后3年BMFS的独立危险因素,而ER阳性(风险比为0.464,P=0.001)是术后3年BMFS的保护性因素。结论 :BSP与浸润性乳腺癌早期骨转移显著相关,BSP阳性与肿瘤直径>3 cm是浸润性乳腺癌早期骨转移的独立危险因素;而ER阳性可能是浸润性乳腺癌早期骨转移的保护性因素。

Objective： To investigate the association between bone sialoprotein （BSP）, human epidermal growth factor receptor 2 （HER-2）, estrogen receptor （ER）/progesterone receptor （PR）, Ki-67 and other clinicopathological features with early bone metastasis in invasive breast cancer, and to analyze the prognostic factors for 3-year bone metastasis-free survival （BMFS） in invasive breast cancer. Methods： A total of 171 patients with invasive breast cancer from Department of Medical Oncology of Fourth Hospital of Hebei Medical University between January 1 and December 31, 2009 were included in this study. Immunohistochemistry （SP method） was used to determine the immunoreactivities to BSP, HER-2, ER, PR and Ki-67 antibodies in resected breast cancer tissues of 171 patinets, and the information regarding clinical and pathological features of all patients were also collected. According to the follow-up, the patients were divided into bone metastasis （BM） group and non-bone metastasis （non-BM） group. Three-year BMFS rate was applied as an early indicator of bone metastasis. The differences in clinical and pathological features including BSP between BM group and non-BM group were estimated by chi-square test. Three-year BMFS was analyzed by log-rank method while comparing the survival curves. The prognostic impacts of clinicopathological features and the biomarker expression on 3-year BMFS were evaluated by Kaplan-Meier method and COX proportional hazards model. Results： The BSP-positive expression rate of BM group was 67.4%, significantly higher than that of no-BM group （44.3%, P = 0.002）. BSP expression was independent of age, tumor size, number of metastatic lymph nodes, TNM stage, Ki-67, and ER, PR and HER-2 expression （all P 〉 0.05）. Univariate analysis showed that 3-year BMFS rate of patients with BSP-positive was significantly lower than that of BSP-negative patients （47.42% vs 68.92%, P = 0.001）, and 3-year BMFS rate of patients with tumor diameter 〉 3 cm was significantly lower than that of tumor diameter ≤3 cm （49.15% vs 62.50%, P = 0.014）, while 3-year BMFS rate of ER-positive patients was significantly higher than that of ER-negative patients （63.56% vs 41.51%, P = 0.027）. Multivariate analysis showed that BSP-positive expression （hazard ratio： 2.179, P = 0.000） and tumor size 〉 3 cm （hazard ratio： 1.580, P = 0.011） were independent risk factors for 3-year BMFS, while ER-positive status was independent protective factor for 3-year BMFS （hazard ratio： 0.464, P = 0.001）. Conclusion： BSP is significantly associated with early bone metastasis of invasive breast cancer; BSP-positive and tumor size 〉 3 cm were independent risk factors for early bone metastasis of postoperative invasive breast cancer, while the ER-positive may be the protective factor of early bone metastasis of postoperative invasive breast cancer.