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OBJECTIVE: As cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors, which play a crucial role in the cell cycle, palbociclib and ribociclib are two novel drugs that are recently being used in the treatment of breast cancer. Despite targeting the same pathway, these agents have different molecular activities and processes. KI-67 is known to play a significant role in cell proliferation that has been related to prognosis. This study investigated the impact of palbociclib, ribociclib, and KI-67 on toxicity and survival in breast cancer treatment. PATIENTS AND METHODS: The study included 140 breast cancer patients in total. Patients were divided into groups based on the use of different CDK inhibitors and KI-67 values. Mortality, progression, treatment response rates, frequency, and severity of adverse events were assessed retrospectively. RESULTS: The patients in our study had an average age of 53.62±12.71 years, and 62.9% of them were diagnosed at an early stage. 34.3% (n=48) of the patients progressed after receiving treatment, while 19.3% (n=27) of the patients died. The median follow-up time was 576 days, the maximum follow-up time was 1,471 days, and the median time to progression was 301 days (min=28-max=713). Mortality, progression, and treatment response rate between two different CDK inhibitors or KI-67 groups revealed no statistically significant differences. CONCLUSIONS: Our data show a comparison between the effectiveness of palbociclib and ribociclib, and no noticeable difference is found in breast cancer patients’ survival, progression, or severity of adverse effects. Likewise, there is no meaningful difference in KI-67 expression subgroups between progression and survival following treatment. [ABSTRACT FROM AUTHOR]