Alexandra Zimmer, MD, MSc
Associate Research Physician
In this edition of Grand Rounds in Hematology and Oncology from October 2021, Patrick M. Dillon, MD, University of Virginia Hematology & Oncology, Charlottesville, Virginia, introduces Alexandra Zimmer, MD, MSc, Associate Research Physician – NCI/NIH, Bethesda, Maryland. In this 58-minute presentation, Dr. Zimmer provides an in-depth exploration of brain metastases in breast cancer, emphasizing the challenges in management and evolving treatment strategies, outlining the clinical complexities associated with HER2-positive, triple-negative, and hormone receptor-positive breast cancers and their distinct metastatic patterns and treatment responses.
Dr. Zimmer begins by noting the aggressive nature of triple-negative breast cancer, which frequently involves rapid progression and poor outcomes once brain metastases develop. In contrast, HER2-positive breast cancer patients often present with isolated brain metastases without systemic disease progression, underscoring the unique behavior of this subtype. Hormone receptor-positive breast cancer, while less prone to brain metastases, tends to manifest cerebral involvement later in the disease course after multiple lines of therapy.
Dr. Zimmer underscores the evolving landscape of systemic therapies for brain metastases. She outlines the limited but notable impact of systemic agents such as capecitabine, trastuzumab, and TKIs in managing these patients. Of note, she highlights the success of the HER2CLIMB trial, which demonstrated that tucatinib significantly improves progression-free and overall survival in patients with HER2-positive breast cancer and brain metastases. This trial’s inclusion of patients with active CNS disease is emphasized as a crucial step toward addressing the previously unmet need for effective systemic therapies in this population.
Dr. Zimmer also highlights ongoing challenges in treating triple-negative breast cancer brain metastases, where options remain limited. Emerging agents such as sacituzumab govitecan may offer promise, though more data is required.
Dr. Zimmer calls for better integration of patients with brain metastases in clinical trials, improved CNS-targeted agents, and a focus on developing predictive biomarkers to identify patients at higher risk for brain progression. The insights in this presentation reflect a growing emphasis on tailored therapies that address systemic and CNS disease in breast cancer management.