This study analyzed 147 patients with hormone receptor-positive and HER2-positive metastatic breast cancer (HR+/HER2+ MBC) who received first-line chemotherapy and dual anti-HER2 therapy using a real-world registry dataset. The efficacy of adding endocrine therapy to dual anti-HER2 therapy after chemotherapy discontinuation was studied retrospectively. The researchers discovered that endocrine therapy resulted in statistically significant and clinically meaningful improvements in both PFS and overall survival outcomes. In the first-line treatment of HR+/HER2+ MBC, the current standard practice is to administer a CLEOPATRA trial-based regimen that includes taxane, pertuzumab, and trastuzumab until the best response is achieved and then discontinue chemotherapy. These findings, with a hazard ratio of 0.52 for overall survival with the addition of endocrine therapy, confirm that all patients with HR+/HER2+ MBC should receive endocrine therapy after achieving the best response with chemotherapy.