New insights into the prognostic value of Ki-67 labeling index in patients with triple-negative breast cancer
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Shuang Hao1,2,*, Zhi-Xian He3,*, Ke-Da Yu1,2, Wen-Tao Yang2,4, Zhi-Min Shao1,2,5,6
1Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
3Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
4Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
5Institutes of Biomedical Science, Fudan University, Shanghai, China
6Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
*These authors contributed equally to this work
Zhi-Min Shao, e-mail: firstname.lastname@example.org
Ke-Da Yu, e-mail: email@example.com
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
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 HRKi67 > 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.
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