Analysis Of Clinicopathological Features And Prognostic Factors Of Bisphosphonates-Treated Breast Cancer Patients With Bone Metastasis

Objective: To analysis the clinical and pathological characteristics of patients with bone metastatic breast cancer, and search for the metastatic and treated features and prognostic factors in these patients.Methods: We retrospectively analyzed the clinical and pathological features of 183 bone metastatic advanced breast cancer patients who had received bisphosphonates for ?6 months from January 2005 to April 2013 in Tianjin Medical University Cancer hospital, in order to analysis the features of bone metastasis, the skeletal-related events, the characteristics of treatment and prognostic factors. On the basis of the BP type, patients were divided into three groups with pamidronate, zoledronate, or sequential therapies group. The statistical analysis was performed using SPSS software version 22.0. The ?2 test was used to compare the data among groups. The survival curve was made by Kaplan-Meier method. Single factor analysis and multiple-factor analysis of survival difference between groups were performed by the log-rank test and by the Cox regression model.Results: The median age at diagnosis with breast cancer in 183 patients was 46 years, while the median age at diagnosis with bone metastases was 50 years. Invasive ductal carcinoma was the most common pathological type in all patients, immunohistochemical results showed that the status of hormone receptor was positive in 80.9%(148/183) patients, while HER-2 was positive in 15.8(29/183) patients. The median time from surgery to bone metastases was 42.3(range: 0-244.9) months, thoracic vertebrae and ribs were the most common sites of bone metastases, while limbs and skull were the least sites of bone metastases. Only 10.9% patients(20/183) were bone metastases only, 73.2% patients(134/183) were bone metastases with visceral metastases, and 15.8% patients(29/183) were bone metastases with non-visceral metastases.51.9%(95/183) patients occurred SREs, the median time from bone metastases to occur the first SREs was 4.2(0-113.5) months. The accumulative total number of SREs was 167 times, among these 110 times occurred in one year after bone metastasis, the incidence of bone radiation was the highest, followed by pathologic fracture. The incidence rate of SREs after different BPs used(excluding the SREs occurred before BPs used) was compared, the incidence rate of SREs was 36.8%(25/68) in pamidronate group and 51.2%(22/43) in zoledronate group and 51.4%(37/72) in pamidronate sequential zoledronate therapies group, the result showed that no statistical difference was found among three groups(P>0.05). In the subgroup analysis of 84 patients who used bisphosphonates for more than 2 years, the results showed that the incidence of SREs decreased significantly after using bisphosphonates for one year.The median overall survival after bone metastases of all the 183 patients was 43.1 months. The 3- and 5-year survival rates were 58.9% and 39.1%. Monofactorial analysis demonstrated that the lymph node metastasis, clinical stage, hormone receptor status, DFS, visceral metastases and vertebral metastases were prognostic factors in bone metastatic breast cancer patients. In multivariate analysis, the hormone receptor status, DFS, visceral metastases and vertebral metastases were independent predictors for survival in bone metastatic breast cancer patients(P<0.05). The median bone metastases-overall survival was 49.7 months in ER/PR positive patients and 25.7 months in ER/PR negative patients, the survival of ER/PR positive patients was much better than ER/PR negative patients. Furthermore, the median bone metastases-overall survival of patients who had longer DFS(?36 months) was 55.3 months compared to 33.6 months in those patients who had shorter DFS(<36 months). Patients without visceral metastases or vertebra metastases had better survival than those with visceral metastases or vertebra metastases.Conclusions: Bone metastases is the common metastatic sites in advanced metastatic breast cancer, thoracic vertebrae and ribs were the most common sites of bone metastases in breast cancer patients. SREs was a common complication of breast cancer patients with bone metastases, SREs mainly occurred in one year after bone metastasis, bone radiation was the main SREs. The incidence of SREs decreased significantly after using bisphosphonates for one year. There is no statistical difference in the incidence rate of SREs after different BPs used among the pamidronate group, the zoledronate group and the pamidronate sequential zoledronate therapies group. The median overall survival of bone metastatic breast cancer patients was 43.1 months. The 3-year and 5-year survival rates were 58.9% and 39.1%. The negative hormone receptor status, disease-free survival < 36 months, visceral metastases and vertebral metastases were independent predictors of poor survival in bone metastatic breast cancer patients.