Assessment of Ki67 and uPA/PAI-1 expression in intermediate-risk early stage breast cancers

Abstract

BackgroundThe objective of this study was to compare the efficacy of biomarkers in assessing the risk of breast cancer recurrence in patients with node-negative or micrometastatic grade II breast cancer. Specifically, we compared risk assessments based on the St. Gallen clinicopathological criteria, Ki67 expression and urokinase plasminogen activator (uPA)/plasminogen activator inhibitor-1 (PAI-1) expression.MethodsThis retrospective study included 347 patients with breast cancer followed at Limoges University Hospital. The optimal cut-off for high Ki67 expression (Ki67hi) was established as 20%. The threshold for uPA and PAI-1 positivity was 3 ng/mg and 14 ng/mg, respectively.ResultsKi67 expression was lower in uPA/PAI-1-negative than in uPA/PAI-1-positive tumours (227 tumours; P = 0.04). The addition of Ki67 status to the St. Gallen criteria resulted in a 28% increase in the rate of identification of high-risk tumours with a potential indication for chemotherapy (P < 0.001). When considering uPA/PAI-1 levels together with the St Gallen criteria (including Ki67 expression), the number of cases identified as having a high recurrence risk with a potential indication for adjuvant chemotherapy increased by 20% (P < 0.001). Adjuvant chemotherapy was 9% less likely to be recommended by a multidisciplinary board when using the current criteria compared with using a combination of the St. Gallen criteria and Ki67 and uPA/PAI-1 status (P = 0.03).ConclusionsTaken together, our data show discordance among markers in identifying the risk of recurrence, even though each marker may prove to be independently valid.

Independent validation of stromal uPA in ABCSG-08: Level 1b evidence for the prognostic value of uPA immunohistochemistry

“…Individual Ki67 values were therefore not available for uni- and multivariate analysis. This is important in the light of two recent publications which demonstrated that Ki67 expression was lower in uPA/PAI-1-negative than in uPA/PAI-1-positive tumors [ 26 , 27 ]. Furthermore, the subset of patients with available and thus analyzable tumor tissue was only a relatively small fraction of the overall trial population of 3714 women who had been randomized into the trial, thus potentially obscuring a potential prognostic effect of the uPA/PAI1 ratio, simply because not enough DDFS events had occurred.…”

Levels of uPA and PAI-1 in breast cancer and its correlation to Ki67-index and results of a 21-multigene-array

“…Links are known to exist between the Ki67 index and the values for uPA/PAI-1. Deluche et al found lower Ki67 indices with negative uPA/PAI-1 than with increased values, with the threshold between low and high Ki67 being set at 20% [ 22 ]. They observed that when both parameters were taken into account in therapy planning, 9% fewer patients were received a recommendation for adjuvant chemotherapy than in cases where only the St. Gallen criteria were used.…”

Breast Cancer18F-ISO-1 Uptake as a Marker of Proliferation Status

“…Spearman rank correlation was used to estimate the strength of association between tracer uptake and Ki-67. The threshold for high versus low Ki-67 was defined as 20%, based on a 2017 study of earlystage breast cancers (29) and the 2015 St. Gallen meeting consensus (30). In addition, a 14% Ki-67 threshold was also examined based on the earlier 2011 St. Gallen meeting consensus (31).…”

“…Representative images from tumors with a low and high Ki-67 proliferative status (Ki-67 , or $ 20%) (29,30) are shown in Figures 1 and 2, respectively. Plots of tumor SUV max grouped by high and low Ki-67 (n 5 29) are depicted in Figure 3A.…”