BACKGROUND: The 2018 American Society of Clinical Oncology/College of American Pathologists guidelines classified immunohistochemistry (IHC) 1+ or 2+, FISH-negative breast cancer as HER2-low. To date, only a few studies have investigated the role of HER2-low status in patients with hormone receptor positive/HER2 METHODS: This is a multicentre, retrospective cohort study analysing data from patients with HR RESULTS: Of the 241 patients included, 240 (99.6%) were women. The median age at diagnosis was 57 years (IQR 48-65 years). Most patients had pM M0 (70.5%). At presentation, 112 (46.5%) had HER2-low and 129 (53.5%) had HER2-0 status. CDK4/6i were administered as first-line therapy in 89.2% of patients and as second-line therapy in 10.8% of patients, with palbociclib (61.4%) being the most common. The median progression-free survival during CDK4/6i therapy was 36.3 months (95% CI 23.6 months to not reached), while the median overall survival was 60.5 months (95% CI 54.4 months to not reached). Progression-free survival differed significantly between palbociclib and abemaciclib/ribociclib (24.4 CONCLUSION: CDK4/6i are effective in both HER2-low and HER2-0 MBC, with HER2-low potentially benefiting more from first-line therapy.