Prognostic factors for skeletal complications from metastatic bone disease in breast cancer

Abstract

Conflicts of InterestJanet Brown has received speakers bureau honoraria from Novartis and Amgen and has served as a consultant and/or on advisory boards for Novartis, Amgen, Roche, and Bristol-Myers Squibb.Richard Cook has served as a consultant and/or on advisory boards for Novartis and Abbott.Allan Lipton has received commercial research grants from Novartis, Monogram Biosciences, and Oncogene Science; has received speakers bureau honoraria from Novartis, Amgen, and Genentech; has served as a consultant and/or on advisory boards for Novartis, Amgen, Galapagos, Acceleron Pharm, and has given expert testimony for Novartis.Luis Costa has received speakers bureau honoraria from Novartis and has served as a consultant and/or on advisory boards for Novartis and Amgen.Robert Coleman has received other commercial support from Novartis; speakers bureau honoraria from Novartis and Amgen; has served as a consultant and/or on advisory boards for Novartis, Amgen, Pfizer, and Roche; and has previously given expert testimony on the behalf of Novartis. Previously defined prognostic factors may not reflect current treatment standards and the use of antiresorptive therapies. We report a comprehensive multivariate analysis of potential prognostic factors for skeletal-related events (SREs) using data from a phase III, randomized study of zoledronic acid in patients with bone metastases from BC. Methods:The trial evaluated the number and timing of SREs (pathologic fracture, palliative radiotherapy to bone, surgery to bone to treat or prevent a fracture, and spinal cord compression) and assessed variables for prognostic significance in univariate and multivariate Cox regression analyses. Continuous variables were categorized with predefined cutpoints. All associations with P < .05 were considered significant. A total of 444 zoledronic acid-treated patients with assessments of biochemical markers of bone metabolism and complete baseline variable data were included.Results: Significant baseline prognostic factors for occurrence of a first SRE by multivariate analyses included age, pain score, prior history of an SRE, predominant lesion type, elevated bone-specific alkaline phosphatase, and lactate dehydrogenase.Prior fracture was found to be prognostic in a reduced multivariate analysis of time to first fracture, but not for time to first palliative radiotherapy. Conclusions:This model identified several prognostic factors that may be useful in routine clinical care. Validation of these factors in a separate dataset and generation of a prognostic risk score are recommended next steps.

Serum Lactate Dehydrogenase Is Prognostic for Survival in Patients with Bone Metastases from Breast Cancer: A Retrospective Analysis in Bisphosphonate-Treated Patients

“…Because these variables have been well recognized as factors prognostic for survival in patients with metastatic breast cancer (14,31), they provide validation for the methodology used in the current analyses. Univariate and multivariate analyses have identified baseline bone biomarker levels such as NTX and BSAP as prognostic factors for occurrence of SREs in patients with bone metastases (24,32). However, although both NTX and BSAP were significantly correlated with risk of death in the univariate model in the current analysis, this statistically significant correlation was not maintained for either biomarker in the multivariate model (Table 2).…”

“…22; Table 1; ref. 24). The majority of patients (81%) were less than 70 years of age, had some impairment in ECOG-PS (65%), had a prior SRE (59%), and had received prior chemotherapy (76%).…”

“…A recent multivariate analysis of baseline variables in this trial identified prognostic factors for SRE risk including age, pain score, prior history of an SRE, predominant lesion type, elevated bone-specific alkaline phosphatase (BSAP), and elevated lactate dehydrogenase (LDH; ref. 24). The current exploratory analysis uses data collected prospectively in the above trial and was conducted to investigate prognostic variables for OS among patients with bone metastases from breast cancer enrolled in the ZOL arm of the pamidronate-controlled trial.…”

The factors that have an impact on the development of brain metastasis in the patients with breast cancer

“…[34] Bisphosphonates, which are commonly used in the therapy, are the leading important factors that slow down the progression of the bone metastasis. [35] While it was predicted that brain metastasis would be less frequently seen in the presence of bone metastasis which has a better course compared to other organ metastasis, some studies did support this hypothesis. [36] In patients with bone metastasis, we found that brain metastasis was less common.…”

Acidic microenvironment and bone pain in cancer-colonized bone

“…[3][4][5][6] and are eventually associated with skeletal-related events (SRE) including pathologic fractures, hypercalcemia, spinal cord compressions, palliative radiotherapy to bone and surgery to bone to treat or prevent a fracture during the clinical course of the disease. 7 However, the most common and detrimental SRE associated with cancer colonization in bone is the bone pain. 8 Although not all patients with bone metastases experience cancer-associated bone pain (CABP), 470% of cancer patients with metastatic bone disease suffer from severe CABP in advanced stages.…”