Prognostic and predictive impact of Ki67 expression in triple-negative breast cancer

Aim/Background

Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and subypting is necessary to better identify molecular-based therapies. The purpose of this study was to investigate the role of Ki67 in further classification of TNBC into subtypes with different prognosis, and whether these subtypes could benefit from carboplatin.

Methods

From January 2004 to December 2012, 363 continuous TNBC patients were identified from the institutional clinical database. The Log-rank test were used to assess impact of different factors on disease-free survival (DFS) and overall survival (OS). A multivariate Cox proportional hazards regression model was performed to analyze the independent prognostic factors. Interaction between use of carboplatin and Ki67 was graphically evaluated by use of Sub population Treatment Effect Pattern Plot (STEPP) methodology.

Results

High Ki67 index (defined as >40%) was more common in younger age (P < 0.001), and was associated with worse differentiation (p < 0.001).High Ki67 patients received more chemotherapy than the low Ki67 group (p =0.007). After a median follow-up time of 34 months (5.2-120.0 months), 62 patients (17.1%) had relapses and 33 patients (9.1%) died of breast cancer. In univariate analysis, high Ki67 index as well as larger tumor size and lymph node involvement was associated with shorter DFS and OS. In multivariate analysis, Ki67 is an independent prognostic factor for DFS (Risk Ratio, RR: 2.835, 95% confidence interval, 95% CI: 1.586-5.068, P < 0.001) and OS (RR: 3.180, 95% CI: 1.488-6.793, P = 0.003). When analyzing the 3-year DFS by Ki67 distribution, STEPP analysis showed a possible beneficial effect of carboplatin in patients with high Ki67 index.

Conclusions

TNBC is probably a heterogeneous disease with different characteristics and prognosis, and may be further stratified according to the Ki67 expression levels. Patients in the high Ki67 group seem to benefit from treatment with carboplatin, but this needs to be further verified.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.