Abstract
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(-) (HR(+)/HER2(-)) metastatic breast cancer (MBC) during CDK4/6 inhibitor (CDK4/6i) therapy. METHODS: This is a multicentre, retrospective cohort study analysing data from patients with HR(+)/HER2-low and HR(+)/HER2-0 MBC treated with CDK4/6i as first-line or second-line therapy at the Oncology Units of IRCCS San Matteo Hospital and ICS Maugeri IRCCS in Pavia, Italy, from January 2017 to October 2023. The aim was to assess the activity and effectiveness of CDK4/6i in a real-life setting. 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 versus 53.7 months; p=0.0109) and between first-line and second-line therapy (40.5 versus 21.2 months; p=0.0466). CONCLUSION: CDK4/6i are effective in both HER2-low and HER2-0 MBC, with HER2-low potentially benefiting more from first-line therapy.