Despite major advances in the targeted treatment of human epidermal growth factor receptor 2 (HER2)–positive breast cancer, the management of CNS metastases in patients with advanced disease is an increasingly common challenge. Large adjuvant trastuzumab trials have demonstrated that 2% to 4% of patients with early-stage HER2-positive breast cancer develop CNS metastases as the first site of relapse. Although the risk of relapse is highest in the first 3 years, CNS relapses have been observed out to year 10. In the metastatic setting, more than 30% of patients diagnosed with stage IV HER2-positive breast cancer develop CNS involvement, most within the first 3 years of their metastatic diagnosis. It has been well established that patients with breast cancer brain metastases (BCBM) have a worse quality of life, reduced progression-free survival (PFS), and shorter overall survival (OS) compared with those without CNS involvement. Identifying regimens to improve outcomes for this poor prognostic subset of patients remains a considerable unmet need in breast cancer.
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