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. This study investigates the prevalence and prognostic impact of somatic mutations on survival and neurological outcomes in metastatic breast cancer to the spine (MBCS).

Methods: A retrospective review was conducted of the medical records and molecular genetic profiles of 50 patients diagnosed with MBCS between May 2013 and October 2022 at Johns Hopkins. Patients diagnosed with MBCS who had undergone genetic profiling were included in the study. Overall survival rates, identification of genetic biomarkers, neurological outcomes via Frankel scores, and the impact of various anticancer therapies were the primary outcomes measured.

Results: The median age of patients was 56 years, with a mortality rate of 52% and a median survival of 6 years. A total of 99 genetic biomarkers were identified, with ER (38.4%), GATA-3 (32.3%), PR (28.3%), Her2neu (13.1%), and AE1/AE3 (8.1%) being the most common biomarkers. ER, AE1/AE3, and PIK3CA were associated with decreased postoperative Frankel scores (p < 0.05). PR was associated with increased postoperative Frankel score (p=0.048). Estrogen Receptor Status was the only biomarker that was associated with overall survival. Smoking status was associated with decreased survival (TR=0.427; p=0.043), as was treatment with immunotherapy or targeted therapy (TR=0.440; p=0.048). Radiotherapy to spinal metastasis was not correlated with survival (TR=0.256; p=0.121). Eribulin was associated with an increase in survival (TR=3.374; p=0.009), in contrast to pertuzumab (TR=0.390; p=0.010) and capecitabine (TR=0.496; p=0.024), which were both associated with a decrease in survival. There were no differences in overall survival via univariate analysis by age, Ki-67 index, or immunotherapy or targeted therapy use.

Conclusion : The genetic makeup of MBCS might correlate with neurological motor and sensory outcomes, particularly ER, AE1/AE3, PR, and PIK3CA. However, while these biomarkers play a role in neurological prognosis, only ER was associated with overall survival when other confounding factors such as smoking status and treatment type were considered. Notably, smoking was found to be markedly associated with decreased survival, whereas eribulin showed strong promise in extending survival.