New Radiotherapy Regimen Shows Potential to Cure HER2-Positive Breast Cancer

A groundbreaking study published in the Journal of Nuclear Medicine reveals that a novel radioimmunotherapy approach could potentially cure human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The technique, which involves pre-treating tumors before delivering targeted alpha-radioimmunotherapy, achieved durable major responses, including histologic cures, with minimal side effects.

HER2-positive breast cancer, an aggressive subtype affecting 15–20% of patients, remains challenging to treat due to therapy resistance and toxicities from current treatments. “Previous studies have shown that HER2-targeted radioimmunotherapy with the α-particle–emitting radionuclide 225Ac has been effective, but not safe,” said Sarah Cheal, PhD, assistant professor at Weill Cornell Medicine. “In our study, we used a pretargeted radioimmunotherapy (PRIT) approach to directly treat the tumor and prevent potent alpha-particles from being absorbed in healthy tissues.”

The new three-step regimen includes a bispecific anti-HER2/anti-DOTA antibody, a clearing agent, and 225Ac-PRIT. Researchers tested the method in both cell-line and patient-derived breast cancer models. In the BT-474 model, 100% of mice achieved complete responses and 85% achieved histologic cures, with no chronic radiation toxicity observed. One or two treatment cycles proved equally effective. In the patient-derived model, a single treatment produced a 60% complete response and extended survival compared with untreated controls. Researchers also established the dosage threshold for kidney-related toxicity.

“This study illustrates the curative potential of 225Ac-PRIT as a treatment for highly aggressive subtypes of HER2-positive breast cancer,” said Nai Kong Cheung, MD, PhD, of Memorial Sloan Kettering Cancer Center. “If successfully translated to the clinic, HER2-directed 225Ac therapy could offer new treatment options in breast cancer and other HER2-expressing solid tumors.”