HER2+ Maintenance Therapy Approvals and Innovative Brain Metastasis Care Reshape Breast Cancer Management

Breast Cancer Briefing, hosted by Sara Nunnery, MD, MSCI, a breast medical oncologist and the director of Breast Cancer Research at Tennessee Oncology in Nashville, is a podcast series that breaks down the latest news in breast cancer research, one conversation at a time.

In this episode, Dr Nunnery sat down with Sarah L. Sammons, MD, an associate professor of medicine, the co-director of the Breast Cancer Evaluation and Treatment Program, co-leader of Breast Medical Oncology, and the co-director of the Multidisciplinary Brain Metastases Clinic at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center in Baltimore.

The experts discussed the management of HER2-positive metastatic breast cancer and brain metastases. Dr Sammons explained that brain metastases arise when primary breast cancer cells migrate through the bloodstream, noting that HER2-positive and triple-negative breast cancer subtypes carry the highest risk. She argued that current ASCO and National Comprehensive Cancer Network guidelines should be reconsidered to permit screening brain MRIs when findings would change treatment, emphasizing quality-of-life end points over overall survival.

Turning to therapy, Dr Sammons reviewed local treatment options and the evolving understanding of the blood-brain barrier, highlighting that both TKIs and antibody-drug conjugates can penetrate the central nervous system. She then provided insights on data from the phase 3 HER2CLIMB-05 trial (NCT05132582), which supported the October 2026 FDA approval of tucatinib (Tukysa) added to trastuzumab (Herceptin) and pertuzumab (Perjeta) maintenance, extending median progression-free survival vs placebo plus trastuzumab and pertuzumab when administered following induction treatment.

Dr Sammons distinguished maintenance strategies by hormone receptor status, favoring the phase 3 PATINA trial regimen (NCT02947685) for estrogen receptor (ER)–positive disease and the HER2CLIMB-05 regimen for ER-negative disease. She also addressed treatment tolerability considerations, including diarrhea and transaminase elevations.

Finally, the experts contextualized first-line sequencing following the FDA approval of fam-trastuzumab deruxtecan-nxki (Enhertu) plus pertuzumab, discussed leptomeningeal disease, explored the emerging role of circulating tumor DNA, and outlined future research directions, including VEGF bispecific antibodies and novel brain-penetrant agents.