Current indications and future perspectives for antibody-drug conjugates in brain metastases of breast cancer

Breast cancer is one of the main cause of cerebral and leptomeningeal metastases, the prognosis of which remains poor to this day. Most studies excluded patients with active brain metastases (BM) and particularly with leptomeningeal metastases (LM) explaining the lack of therapeutic innovation in this area. Currently, the standard management of patients with BM of breast cancer is based on the combination of surgery, radiotherapy and systemic treatments. Recently, third-generation of Antibody-Drug Conjugates (ADCs), have revolutionized the management of metastatic breast cancer. Trastuzumab deruxtecan and Sacituzumab govitecan have indeed shown significant improvements of survival outcomes and can now be used in a wide range of breast cancer subtypes. However, few data are available on the efficacy of third-generation ADCs on BM and LM of breast cancer. As the field of ADCs is rapidly evolving, with new constructs entering the late clinical development, in this review we describe the efficacy of approved and novel promising conjugates on patients with BM and LM of breast cancer.