Page 74 - Predicting survival in patients with spinal bone metastasesL

CHAPTER V METHODS
In this international multicenter retrospective cohort study, all consecutive breast cancer patients presenting with symptomatic SBM between January 2005 and December 2012 at tertiary referral centers in Leiden, Graz, and Aarhus were included. The primary data sources were the patient’s clinical files, pathology reports and admission forms. ER, PR and HER2 information was obtained from reports at the time of diagnosis of the primary tumor. Due to the fact that the process of decalcification can influence the results of the receptor status determination, only information derived from material of the primary tumor was entered into the study. Receptor information derived from the metastasis was disregarded. In all three participating centers, tumors were considered positive for ER or PR when ≥10% of the tumor cells displayed nuclear staining. Initial screening for HER2 was performed using immunohistochemistry. When results were equivocal (weakly positive; score 2+) additional molecular testing was performed using in situ hybridization. In Leiden, chromogenic in situ hybridization (CISH) was used, whereas in Graz and Aarhus fluorescent in situ hybridization (FISH) was used. All laboratories participated in quality assurance programs during the study period.
Based on the ER, PR and HER2 expression, tumors were further subdivided into four categories; luminal A, luminal B, HER2 and triple negative. The luminal A subtype is ER positive and/or PR positive without HER2 overexpression. The luminal B subtype is ER positive and/or PR positive with HER2 overexpression. The HER2 subtype is ER and PR negative, with HER2 overexpression. Finally, the triple negative subtype is negative for all three receptors. To avoid confounding of our results based on the availability of systemic treatment options, 2005 was chosen as the starting year of this study. At this time, the testing for HER2 status was common practice and guidelines in all participating centers had implemented the routine use of agents such as trastuzumab in both adjuvant and palliative settings.
Statistical analysis
Survival time was calculated as the difference between start of treatment for the spinal metastasis and date of death or last follow-up moment recorded. Survival curves were estimated by using Kaplan-Meier method. Follow-up was assessed by employing the reverse Kaplan-Meier method14. Cox proportional hazard
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