Prognostic role of Ki-67 in high-risk estrogen receptor-positive/HER2-negative early breast cancer: a population-based cohort study

<h3>Background and purpose</h3> Abemaciclib is a CDK4/6-inhibitor approved for adjuvant use in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer with high risk of relapse, defined as N2-N3 disease or high-risk N1 disease. The MonarchE study also included high Ki-67 in combination with N1 disease as a separate study cohort. We investigated the prognostic value of MonarchE risk group criteria, with or without the addition of Ki-67, when applied to a large set of real-world data (RWD). <h3>Materials and methods</h3> We carried out a retrospective cohort study using Breast Cancer Data Base Sweden (BCBaSe) 3.0, a research database including all Swedish breast cancer patients from 2008 to 2020. The cohort included 21 110 ER-positive/HER2-negative breast cancer patients, whereof 12 983 had available Ki-67 data. <h3>Results</h3> Risk groups were defined as N1 low risk, N1 high risk and N2-N3 very high risk, based on MonarchE criteria. Survival analyses showed an increasingly worse prognosis across the three groups for three outcomes including distant disease-free survival (DDFS), breast cancer-specific survival (BCSS), and overall survival (OS). Ki-67 ≥20% was associated with statistically significant worse DDFS, BCSS, and OS in the overall N1 group, but when comparing 5-year survival rates in the N1 group with and without Ki-67 stratification, no clinically meaningful absolute difference in OS was seen. <h3>Conclusions</h3> Our nationwide RWD results support the use of MonarchE's risk group criteria for selection of high-risk ER-positive/HER2-negative breast cancer patients who might derive benefit from adjuvant abemaciclib. The role of Ki-67 in risk stratification seems to be limited and without clear clinical significance.