Prognostic Value of Ki-67 and Progesterone Receptor for Risk Stratification and Outcomes by Adjuvant Chemotherapy in Early Luminal-Type Breast Cancer

Hung-Hsun Chen,1,* Shu-Jyuan Chang,2,* Jung-Yu Kan,1 Fang-Ming Chen,1,3 Chung-Liang Li,1,3 Hidenobu Takahashi,1,3 Shen-Liang Shih,1,3 Ming-Feng Hou,1,3,4 Mei-Ren Pan,2,4 Ping-Fu Yang,1,3,* Chi-Wen Luo1,5 1Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Gangshan Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Cosmetic Science and Institute of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan*These authors contributed equally to this workCorrespondence: Ping-Fu Yang, Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, Tel +886-7-3121101ext 6235, Fax +886-7-3165011, Email [email protected] Chi-Wen Luo, Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, Tel +886-7-3121101ext 2260, Fax +886-7-3165011, Email [email protected]: Risk stratification of hormone receptor–positive (HR+)/HER2-negative early breast cancer remains variable across studies. We aimed to develop and validate an immunohistochemistry (IHC)-based stratification framework (PR10/Ki20) and a quantitative risk score (RS), and to explore clinical outcomes according to receipt of adjuvant chemotherapy (CT).Methods: This retrospective study analyzed a discovery cohort (KMTTH, n = 2633) and an external validation cohort (KMUH, n = 1147). Using prespecified cutoffs, patients were categorized into four groups: low risk (LR; PR ≥ 10% and Ki-67 < 20%), moderate risk 1 (MR1; PR < 10% and Ki-67 < 20%), moderate risk 2 (MR2; PR ≥ 10% and Ki-67 ≥ 20%), and high risk (HiR; PR < 10% and Ki-67 ≥ 20%). A quantitative RS was derived incorporating PR10/Ki20 categories, age, pathological T stage, and lymphovascular invasion.Results: The PR10/Ki20 model demonstrated consistent prognostic performance across cohorts. HiR patients had significantly poorer disease-free survival (DFS) and overall survival (OS), whereas the LR group exhibited favorable outcomes. In the validation cohort, adjuvant CT was associated with improved DFS in the HiR group, whereas no statistically significant association was observed in the LR group. The RS separated patients into high- and low-RS groups with significantly different DFS in both cohorts (KMTTH: P = 0.005; KMUH: P = 0.004).Conclusion: The PR10/Ki20 framework and the derived RS provide reproducible prognostic stratification in HR+/HER2− early breast cancer across two cohorts. In this retrospective analysis, CT use was associated with improved DFS among patients classified as high risk, while no statistically significant association was observed in the low-risk group. These findings may help inform risk-adapted discussions and generate hypotheses for prospective validation regarding treatment selection.Keywords: breast cancer, PR, Ki-67, chemotherapy, risk stratification