Basile D, Gerratana L, Corvaja C, et al. - Given that standard therapy for luminal-metastatic breast cancer (MBC) is endocrine therapy (ET) plus cyclin-dependent-kinases 4/6 inhibitors (CDK4/6i), but there is still an absence of prospective head-to-head comparisons for first line (L) choices, and describing the best strategy between first and second L is still important, thus, researchers undertook this observational, retrospective study with 717 patients treated for luminal metastatic breast cancer. Using log-rank test, disparities regarding survival outcomes (overall survival, progression-free survival and post-progression survival) were examined. As per the real-world data provided, the best choice for first L luminal-MBC is ET-CDKi vs ET and chemotherapy (CT). Also, experts suggest the likely feasibility of second L ET, potentially integrated with other molecules, as a possible choice post-CDK4/6i failure, postponing CT on later lines.