Brain Metastases in the Setting of Stable Versus Progressing Extracranial Disease Among Patients With Metastatic Breast Cancer

Brain metastases (BrM) are common among patients with metastatic breast cancer (MBC), particularly those with HER2 + or triple negative disease. In our single-center retrospective cohort of 691 MBC patients, similar to 40% had stable extracranial disease at the time of BrM diagnosis. Isolated intracranial progression was most common among patients with HER2 + MBC; clinical trials for this patient population are warranted. Introduction: Women with metastatic breast cancer (BC) are at risk of developing brain metastases (BrM), which may result in significant morbidity and mortality. Given the emergence of systemic therapies with activity in the brain, more breast oncology clinical trials include patients with BrM, but most require extracranial disease progression for trial participation. Methods: We evaluated the proportion of patients with BC BrM who have intracranial disease progression in the setting of stable extracranial disease in a retrospective cohort study of 751 patients treated between 2008 and 2018 at the Sunnybrook Odette Cancer. Extracranial disease progression was defined as any progression outside of the brain within 4 weeks of a patient's local/regional treatment. Clinical/pathologic characteristics and outcomes were also abstracted from patients' medical records. Results: Of 752 patients in the cohort, 691 were included in our study. Sixty-one patients were excluded due to the presence of a second primary tumor or uncertain tissue origin of the BrM. BC subtype based on the primary tumor was known for 592 (85.6%) patients; 33.1% (n = 196) had HER2 + disease, 40% (n = 237) had HR + /HER2- disease, and 26.9% (n = 159) had triple negative BC. Extracranial disease status was available for 677 patients (98%); 41.1% (n = 284/691) had stable extracranial disease and 56.8% (n = 393/691) had extracranial disease progression within 4 weeks of treatment for BrM. Discussion: A high proportion of patients with BC BrM (41.1%) would be excluded from clinical trials due to stable extracranial disease. Efforts should be made to design trials for this patient population.