Ki67 Assessment by qRT-PCR in OncotypeDx ® Breast Recurrent Score®: Low Correlation With IHC Assessment of ki67 and Prognostic Impact of ki67 RNA Level of Expression.

Abstract Background: Breast cancers expressing high levels of Ki67 are associated with poor outcomes. To provide individualized patient care, reliability of prognostic and predictive information deriving from Ki67 assessment is essential. Oncotype DX® test was designed for ER+/HER2- early-stage breast cancers to help adjuvant chemotherapy decision by providing a Recurrent Score® (RS®). RS® measures the expression of 21 specific genes from tumor tissue, including Ki67, and aim to predict the benefit of chemotherapy and the risk of distant recurrence. The primary aim of this study was to assess the agreement between Ki67RNA obtained with Oncotype DX® RS® and Ki67IHC. Other objectives were to analyze the association between the event free survival (EFS) and the expression level of Ki67RNA; and association between RS® and Ki67RNA.Methods: In a cohort of 98 patients with early ER+/HER2- breast cancers, we obtained: Recurrence score®, RNA level of Ki67 expression measured when assessing RS® and Ki67 tumor labelling by immunohistochemistry (Ki67IHC). The Ki67RNA was compared to the Ki67IHC by Kappa Cohen test. With a mean follow-up of 57 months, the association between the event free survival (EFS) and Ki67 status was measured using R package survival. Results: This population was essentially composed of no special type tumor (91%), N0 or Nmic (71%), grade 1 (62%), and tumor size pT1c (1-2 cm) (58%). The RS® values were <18 in 38% (n=37), 18-30 in 51% (n=50) and >30 in 11% (n=11) of the patients. A low agreement of 0.24 was found by Cohen’s kappa test between Ki67IHC and Ki67RNA. Moreover, Ki67RNAhigh tumors were significantly associated with the occurrence of events (p=0.02). On the other hand, we did not find any association between Ki67IHC and EFS (p=0.25).Conclusion: We observed of low agreement between expression level of Ki67RNA and Ki67 protein labelling by IHC. Unlike Ki67IHC and independently of the RS®, Ki67RNA could have a prognostic value. It would be interesting to better assess the prognosis and predictive value of Ki67RNA measured by qRT-PCR. The Ki67RNA in medical routine could be a good support in countries where Oncotype DX® is not accessible.