2024 Impact of Somatic Mutations on Survival and Neurological Outcomes in Spinal Metastases from Breast Cancer

INTRODUCTION: Breast cancer remains the leading cause of cancer in women worldwide, with a significant proportion developing osseous metastases in the spine, adversely affecting survival and neurological function. METHODS: The medical records and molecular genetic profiles of 50 patients diagnosed with MBCS between May 2013 and October 2022 at Johns Hopkins were retrospectively queried to collect demographic data, genetic biomarkers, Frankel scores, and details on anticancer therapies. Statistical analyses, including Accelerated Failure Time Models and ordinal logistic regression, were utilized to identify prognostic factors for survival and neurological outcomes. RESULTS: Patient median age was 56 years, with a mortality rate of 52%, and a median survival of 6 years. Out of 99 genetic biomarkers identified, ER (38.4%), GATA-3 (32.3%), PR (28.3%), Her2neu (13.1%), and AE1/AE3 (8.1%) were the most common. ER, AE1/AE3, and PIK3CA were associated with decreased postoperative Frankel scores (p<0.05), and PR with increased postoperative Frankel score (p=0.048). When accounting for treatment type and smoking status, ER was associated with overall survival. Smoking status (TR=0.427; p=0.043) and immunotherapy treatment (TR=0.440; p=0.048) were associated with decreased survival. Microtubule inhibiting agent Eribulin was associated with an increase in survival (TR=3.374; p=0.009), in contrast to HER-2 monoclonal antibody Pertuzumab (TR=0.390; p=0.010) and anti-metabolite Capecitabine (TR=0.496; p=0.024), which were both associated with a decrease in survival. CONCLUSIONS: The genetic makeup of MBCS might correlate with neurological outcomes, particularly ER, AE1/AE3, PR, and PIK3CA. However, only ER was associated with overall survival when considering other confounders. Additionally, survival was influenced by Eribulin, Pertuzumab, and capecitabine. These results warrant further investigation to the utilization of MBCS biomarkers to improve patient neurological symptoms and survival.