Deciphering the role of Ki67: prognostic insights in advanced breast cancer therapy with Cyclin-dependent kinase 4/6 inhibitors

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are the standard of care in advanced breast cancer. While Ki67 is prognostic in early-stage disease, including adjuvant CDK4/6i, its role in metastatic setting is unclear. This study assessed Ki67’s prognostic value in advanced breast cancer treated with CDK4/6i. We conducted a retrospective analysis of patients with advanced breast cancer receiving CDK4/6i at our cancer center between 2018 and 2023. The study included 368 patients with Ki67 results. The median age was 63 years (IQR 52–70.5). 283 patients (76.9%) received CDK4/6i in the first-line. With respect to biopsy timing, Ki67 expression was evaluated in tissue samples from 319 patients in the metastatic setting and 49 patients in the early breast cancer setting. In terms of biopsy site, Ki67 was measured from the breast tumor in 235 patients, from regional lymph nodes in 26 patients, and from various metastatic sites in 107 patients. Ki67, as a continuous variable, correlated with PFS and OS. Specifically, each unit increase in Ki67 was associated with a 1% reduction in PFS and OS. Median PFS in patients with lowKi67 was 33.0 months vs. 22.0 months for highKi67 (p = 0.008). Two-year PFS was 68.3% for lowKi67, vs. 48.4% for highKi67. Median OS was 49.7 months for lowKi67 vs. 39.8 months for highKi67 (p = 0.027). Ki67 appears to be a prognostic factor in advanced breast cancer patients treated with CDK4/6i. Patients with low Ki67 had favorable prognosis.