New insights into the prognostic value of Ki-67 labeling index in patients with triple-negative breast cancer

// Shuang Hao 1, 2, * , Zhi-Xian He 3, * , Ke-Da Yu 1, 2 , Wen-Tao Yang 2, 4 , Zhi-Min Shao 1, 2, 5, 6 1 Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 3 Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China 4 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China 5 Institutes of Biomedical Science, Fudan University, Shanghai, China 6 Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China * These authors contributed equally to this work Correspondence to: Zhi-Min Shao, e-mail: zhimingshao@yahoo.com Ke-Da Yu, e-mail: yukd@shca.org.cn Keywords: triple-negative breast cancer, Ki67 labeling index, breast-cancer specific survival, heterogeneous Received: July 25, 2015      Accepted: February 23, 2016      Published: April 01, 2016 ABSTRACT The clinicopathological importance of the Ki-67 labeling index (LI) in breast cancer has been studied intensely; however, its prognostic significance in triple-negative breast cancer (TNBC) is unclear. We aimed to determine the optimal Ki-67 cut-off point to demonstrate its prognostic relevance for breast-cancer-specific survival (BCSS) in TNBC patients. A total of 571 female TNBC patients underwent diagnosis and surgery at our institution from January 2002 to June 2011. Clinicopathological information for all patients was available and categorized by Ki-67 LI and age at diagnosis. The cut-off values for Ki-67 LI and age were selected using the medians. A varying-coefficient Cox model was used to describe the effect of Ki-67 LI on BCSS outcomes changing with age after adjustment for disease characteristics. For survival analysis, the Kaplan–Meier method and the log-rank test were used. Cox proportional hazards models were applied to determine the association of Ki-67 LI and age with BCSS outcomes after adjustment for disease characteristics. Median age was 50 years, and median Ki-67 LI was 35% (range, 0 – 97.5%). There was no prognostic significance of stratification by Ki-67 LI in all patients. When analyzing age at diagnosis as a continuous variable, the log-transformed HR Ki67 > 35% vs. ≤ 35% for BCSS increased in an S-shaped curve with increasing age up to about 50 years-old and remained higher-risk for high Ki-67 LI. After adjusting for clinicopathological risk factors, low Ki-67 LI was a poor prognostic factor for BCSS (HR: 0.36, 95% CI: 0.14–0.96, P = 0.042) in patients of ≤ 50 years, but not in patients diagnosed at > 50 years (hazard ratio [HR]: 1.57, 95% CI: 0.76–3.22, P = 0.241). In conclusion, lower Ki-67 LI has poor prognosis relevance in TNBC patients diagnosed at ≤ 50 years-old. Further validation of the clinical significance of Ki-67 LI in TNBC is required.