Evaluation of an Optimal Cut-Off Point for the Ki-67 Index as a Prognostic Factor in Primary Breast Cancer: A Retrospective Study

Abstract

The Ki-67 index is an important biomarker for indicating the proliferation of cancer cells and is considered to be an effective prognostic factor for breast cancer. However, a standard cut-off point for the Ki-67 index has not yet been established. Therefore, the aim of this retrospective study was to determine an optimal cut-off point in order to establish it as a more accurate prognostic factor. Immunohistochemical analysis of the Ki-67 index was performed on 4329 patients with primary breast cancer from August 1987 to March 2012. Out of this sample, there were 3186 consecutive cases from September 1997 with simultaneous evaluations of ER, PgR and HER2 status. Cox's proportional hazard model was used to perform univariate and multivariate analyses of the factors related to OS. The hazard ratios (HR) and the p values were then compared to determine the optimal cut-off point for the Ki-67 index. The median Ki-67 index value was 20.5% (mean value 26.2%). The univariate analysis revealed that there was a statistically significant negative correlation with DFS and OS and the multivariate analysis revealed that the Ki-67 index value was a significant factor for DFS and OS. The top seven cut-off points were then carefully chosen based on the results of the univariate analysis using the lowest p-values and the highest HR as the main selection criteria. The multivariate analysis of the factors for OS showed that the cut-off point of 20% had the highest HR in all of the cases. However, the cutoff point of 20% was only a significant factor for OS in the Luminal/HER2- subtype. There was no correlation between the Ki-67 index value and OS in any of the other subtypes. These data indicate that the optimal cut-off point of 20% is the most effective prognostic factor for Luminal/HER2- breast cancer.

Ki-67 protein expression and tumor associated inflammatory cells (macrophages and mast cells) in canine colorectal carcinoma

“…Ki-67 index was strongly ( r  = 0.71; p  < 0.05) correlated with tumor malignancy. The results suggest association of Ki-67 with malignancy in canine CRC as was previously reported for human CRC [2, 15], prostate and breast cancers [14, 32] and various animal tumors [30, 33–35]. Because, there are genetic and pathogenic similarities between canine CRC and the human disease [36], in which Ki-67 prognostic value remained controversial [1, 14], its prognostic value in canine CRC is unknown at this time.…”

FISH testing of HER2 immunohistochemistry 1+ invasive breast cancer with unfavorable characteristics

“…In the present study, when the Ki-67 index was >30%, it was considered high. It must be highlighted that numerous cut-off values have been proposed in the literature (37,38), and that the reproducibility of the test for Ki-67 is still far from being elevated, due to an important inter-observer and inter-laboratory variability (38). Recently, Goldhirsch et al (39) classified the Ki-67 index into three classes, considering as cut-off value the presence of ≥20% of neoplastic, invasive Ki-67-positive cells.…”

Palbociclib in combination with letrozole as first‐line treatment for advanced breast cancer: A Japanese phase II study

“…Additional assessments included safety and tolerability, evaluation of health‐related quality of life (not reported), determination of plasma C trough of palbociclib combined with letrozole in all patients, and evaluation of the full PK profile of palbociclib in a subset of treated patients (n = 6). We also characterized biomarkers of tumor sensitivity and/or resistance in tumor tissue samples, such as the Ki‐67 index, for which a 20% cutoff has been determined to be optimal (a significant factor for overall survival), or the most effective prognostic factor for luminal/HER2− breast cancer based on a study of 4329 Japanese patients with primary breast cancer …”

“…We also characterized biomarkers of tumor sensitivity and/or resistance in tumor tissue samples, such as the Ki-67 index, for which a 20% cutoff has been determined to be optimal (a significant factor for overall survival), or the most effective prognostic factor for luminal/HER2À breast cancer based on a study of 4329 Japanese patients with primary breast cancer. 19 The study protocol was approved by the Institutional Review Board at each participating center, and written informed consent was obtained from all patients before enrollment. The study was conducted according to applicable local laws and regulatory requirements, the International Conference on Harmonisation Good Clinical Practice guidelines, and the Declaration of Helsinki.…”