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 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.
Highlights
Triple-negative breast cancer (TNBC), as defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression, corresponds to 10%–20% of all breast cancers [1]
TNBC is a heterogeneous disease with distinct molecular subtypes that display unique biology and outcomes, which may lead to variation in the significance of Ki-67 labeling index (LI)
Only nodal status was significantly correlated with breast-cancerspecific survival (BCSS) after adjustment for clinicopathological risk factors
Summary
Triple-negative breast cancer (TNBC), as defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression, corresponds to 10%–20% of all breast cancers [1]. This heterogeneous disease is generally more aggressive, with higher risk of relapse and poorer prognosis as a result of metastatic disease [2, 3]. Ki-67 expression varies throughout G1, S, G2, and M cell cycle phases, but not during the G0 resting phase [5] It has been explored in www.impactjournals.com/oncotarget breast cancer and other malignant diseases. TNBC is a heterogeneous disease with distinct molecular subtypes that display unique biology and outcomes, which may lead to variation in the significance of Ki-67 LI
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