HER2-Positive Breast Cancer With Brain and Leptomeningeal Metastases Responding to Intrathecal Treatment

What happened, in summary

A 40-year-old woman was diagnosed with HER2-positive breast cancer in September 2019. She received chemotherapy before surgery, then underwent breast surgery followed by additional chemotherapy, radiation, and several HER2-targeted treatments. Brain metastases were found in October 2020 and treated with local radiation. When the brain disease progressed again in 2024, she received whole-brain radiation.

In June 2024 she developed numbness affecting the right side of her head and arm together with an abnormal gait. Tumor cells were found in her cerebrospinal fluid, confirming leptomeningeal metastases, and imaging also showed multiple brain lesions. She began treatment delivered directly into the spinal fluid with pemetrexed plus a PD-1 inhibitor. Additional focal radiation was used for selected brain and brainstem lesions.

After 8 intrathecal treatments, her neurological symptoms completely resolved and brain lesions had markedly decreased. Cerebrospinal-fluid testing became negative. Some lesions enlarged slightly by November 2024, but she did not meet criteria for progression, so monthly maintenance treatment continued. As of February 2025, she remained on intrathecal therapy and trastuzumab deruxtecan. This documented follow-up places her more than 5 years beyond her September 2019 breast-cancer diagnosis while still receiving active treatment.