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

Elise Deluche, Laurence Venat-Bouvet, Sophie Leobon, Veronique Fermeaux, Joelle Mollard, Nadira Saidi, Isabelle Jammet, Yves Aubard, Nicole Tubiana-Mathieu

The 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. This retrospective study included 347 patients with breast cancer followed at Limoges University Hospital. The optimal cut-off for high Ki67 expression (Ki67(hi)) was established as 20%. The threshold for uPA and PAI-1 positivity was 3 ng/mg and 14 ng/mg, respectively. Ki67 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). Taken together, our data show discordance among markers in identifying the risk of recurrence, even though each marker may prove to be independently valid.