Dr Sammons on the Investigation of Brain Metastases in HER2+ Breast Cancer

Sarah Sammons, MD, associate director, Metastatic Breast Cancer Program, Dana-Farber Cancer Institute, discusses the background of examining brain metastases in HER2-positive breast cancer, highlighting the implications of these data.

Research presented at the 2023 San Antonio Breast Cancer Symposium delved into an examination of data sourced from the United States Flatiron Health de-identified database, encompassing a cohort of 18,075 patients. Within this dataset, 3062 patients exhibited hormone receptor (HR)–positive, HER2-positive disease, and 902 patients displayed HR-negative, HER2-positive disease. The findings elucidated that the incidence of brain metastases notably varied across different tumor subtypes and treatment lines among all breast cancer cases.

Brain metastases pose a treatment challenge in HER2-positive breast cancer, Sammons begins, adding that retrospective clinical trials indicate that approximately 30% of patients with HER2-positive breast cancer will develop brain metastases during their disease trajectory. The rate of brain metastases occurrence varies depending on HR status, and patients with HR-positive/HER2-positive metastatic breast cancer face an approximate 23% risk of developing brain metastases. However, this risk tends to be slightly higher in patients with solely HER2-driven disease, Sammons explains. Deferring local therapy, particularly in patients with HER2-positive brain metastases, remains an evolving aspect of disease management, according to Sammons.

ASCO issued guidelines in 2021 outlining disease scenarios suitable for considering the deferral of local therapy in patients with HER2-positive brain metastases, she continues. This decision requires a multidisciplinary approach involving input from a radiation oncologist and potentially a neurosurgeon, along with the patient's involvement, Sammons says. Deferral may be considered in cases with a favorable prognosis, Sammons adds. Criteria for deferral include the presence of asymptomatic brain metastases measuring less than 2 cm, the absence of symptomatic mass effect, and the availability of systemic therapy with a high intracranial response rate, she elucidates.

Agents such as tucatinib (Tukysa), capecitabine (Xeloda), trastuzumab (Herceptin), or fam-trastuzumab deruxtecan-nxki (Enhertu), known for their intracranial efficacy, are pivotal treatment considerations, Sammons expands. The feasibility of deferring local therapy in patients with HER2-positive brain metastases is still under evaluation, with certain situations warranting a delay in interventions such as whole-brain radiation or high-volume repeat stereotactic radiation therapy, Sammons explains. The presence of highly effective systemic therapies with demonstrated intracranial response rates prompts further consideration of deferral in appropriate cases, she concludes.