At the San Antonio Breast Cancer Symposium (SABCS), they presented the rationale and design of the ERADICATE study, a first-in-human study evaluating the combination of the oral selective estrogen receptor degrader (SERD) elacestrant with trastuzumab deruxtecan (T-DXd). This combination is being tested in patients with HER2-low metastatic breast cancer. T-DXd is an antibody-drug conjugate (ADC) that demonstrated high efficacy in the DESTINY-Breast01 study in heavily pretreated patients with HER2-positive metastatic breast cancer, with a median progression-free survival (mPFS) of 19.4 months and a median overall survival (mOS) of 29.1 months. In the DESTINY-Breast03 trial, T-DXd achieved better mPFS of 28.8 months vs 6.8 months in T-DM1 (HR PFS 0.33; 95% CI 0.26–0.43; p<0.0001) and better mOS with a 2-year OS rate of 77.4% vs 69.9% (HR OS 0.64; 95% CI 0.47–0.87; p=0.0037). The DESTINY-Breast06 trial confirmed the role of T-DXd in HR-positive disease with low and ultralow HER2 expression, where it improved mPFS to 13.2 months versus 8.1 months with standard therapy.[1][2]