Tips-10 feasibility of a multi-modality central nervous system screening evaluation in her2+ breastcancer patients

Abstract BACKGROUND Breast cancer is the most common cancer in the world and the second most common to metastasize to the central nervous system (CNS). CNS-metastases are the most common type of brain tumor and have a rising incidence. They are associated with neurologic morbidity and mortality and remain a major clinical challenge. Survival withCNS-metastases is short with a median survival in the order of months. The incidence of CNS-metastases is 5.1% in breast cancer however true prevalence is not known; at autopsy this incidence ranges between 20-40%. One contributing factor towards the development of CNS-metastases in breast cancer is HER2-positivity. Between 25%-48% of patients with HER2-positive metastatic breast cancer develop CNS-metastases. Currently, routine CNS surveillance imaging is not recommended, however guidelines suggest having a low threshold for evaluation with imaging and/or cerebrospinal fluid (CSF) analysis because of the high rate of CNS-metastases. The clinical relevance of occult CNS-metastases, survival after identification of occult CNS-metastases and the importance of earlier initiation of CNS therapy are unknown. Existing treatment strategies for CNS-metastases rely on a combinatorial approach of chemotherapy, radiotherapy and/or surgery which typically affords limited disease control. This trial seeks to study if surveillance imaging and CSF analysis are feasible as early disease detection mechanisms. METHODS This is a two-cohort study to establish feasibility of multi-modality CNS surveillance. Patients with HER2+ metastatic breast cancer patients (with no known CNS-metastases) who are either Stage IV (Cohort A) or Stage II/III are eligible (Cohort B). On study, patients will undergo MRI Brain and CSF analysis at 6 monthly intervals. CSF analysis includes cytology, circulating tumor cells and cell-free DNA analysis. We plan to enroll 20 patients (10 onto each cohort). 1 of 20 patients have enrolled. This is the first multi-modality screening feasibility study for patients HER2-positive breast cancer.