ERBB2 and breast cancer: Results of studies that assessed the three marketed CDK4/6 inhibitors showed that combination therapies with endocrine agents (aromatase inhibitors or fulvestrant) significantly improved PFS and OS over the placebo plus endocrine agents in patients with HR + /HER2- metastatic BC in first- and second-line settings, regardless of endocrine therapy strategies, treatment lines, number of metastatic sites, or menopausal status [17, 18].