Hormone receptor (HR)-positive breast cancer with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (HR+/HER2+ breast cancer) is a relatively specific molecular subtype. There is currently no clinical evidence for first-line treatment of HR+/HER2+ advanced breast cancer. For this purpose, the SYSUCC-002 study was conducted. SYSUCC002 is a multicenter, open, randomized, non-inferiority, phase Ⅲ clinical study (NCT01950182) designed to compare the efficacy and safety of endocrine therapy combined with targeted therapy versus chemotherapy combined with targeted therapy. 392 patients with HR+/HER2+ advanced breast cancer were randomized 1∶1 into endocrine therapy (ET) group [endocrine therapy + trastuzumab] and chemotherapy (CT) group (paclitaxel, capecitabine or vinrelbine + trastuzumab). The primary endpoint was progression-free survival (PFS) with a hazard ratio (HR) non-inferiority upper limit of 1.35. The primary endpoint results showed that the median PFS in the CT and ET groups were 19.2 months and 14.8 months, respectively, HR 0.88 (95% CI: 0.71~1.09) (log-rank P=0.250). Secondary endpoint results of the study showed no difference in OS between the two groups. Further subgroup analysis showed that the main factor affecting PFS was disease-free interval (DFI). For patients with DFI≤24 months, those in CT group had better PFS, whereas for patients with DFI>24 months, those in ET group had better PFS (P=0.016). Overall, for HR+/HER2+ advanced breast cancer patients, trastuzumab combined with endocrine therapy was no less effective than trastuzumab combined with chemotherapy, with lower toxicity and better tolerance. With the advent of the dual-target era, the treatment philosophy of endocrine-first principles will continue to guide clinicians' decision making.