Correlation of the oncotype DX breast recurrence score and the ki-67 IHC MIB-1 pharmDX score in HR+, HER2-, node-positive early breast cancer.

Abstract

e12556 Background: In monarchE, abemaciclib, an oral CDK4/6 inhibitor, when combined with endocrine therapy (ET, tamoxifen or aromatase inhibitor) significantly improved invasive disease-free survival in patients with HR+, HER2-, node positive early breast cancer (EBC) at high risk of early recurrence and Ki-67 score ≥20%. The US FDA subsequently approved the Ki-67 IHC MIB-1 pharmDx assay (Dako Omnis) as a companion diagnostic. The Oncotype DX Breast Recurrence Score assay has similarly been validated in HR+, HER2- invasive breast cancers (IBC) to predict chemotherapy benefit and risk of distant recurrence at 10 years regardless of node status. While several studies have previously shown a relationship between Ki-67 IHC assays and RS, this relationship has not yet been evaluated using the standardized Ki-67 assay established for monarchE. The primary objective was to estimate the correlation between the Recurrence Score (RS) result and the monarchE Ki-67 IHC score using prospectively collected node positive, HR+, HER2- IBC specimens. A secondary objective assessed the proportion of node positive, HR+ patients with RS 26-100 that have Ki-67 IHC score >20%. Methods: IBC samples were acquired from Exact Sciences following an IRB-approved protocol. Samples from US patients with HR+, HER2- IBC, 1-3 positive lymph nodes (N1) with available RS result and sufficient tumor content were eligible. After collection of 275 samples with all RS results eligible (“All- RS pool”), 36 more samples with RS 26-100 were collected with high RS (HI RS only”). Unstained tissue sections were subsequently sent to Agilent Technologies for Ki-67 IHC using the monarchE assay. The consensus diagnostic category (positive/negative) and an average of the two closest % positivity scores were used for the final dataset. Spearman rank correlation and cross tabulations of RS result with % Ki-67 were performed according to the predetermined statistical analysis plan. Results: 311 samples were collected, 1 with a null Ki-67 result. Twelve samples had a pathology report with node negative assessment, leaving 298 samples and 262 in the All-RS pool. The rank correlation between % Ki-67 and RS result in the all-RS pool in the node positive population was 0.396 (95% CI 0.288 – 0.493). Cross-tabulations of the Ki-67 diagnostic category (< 20% vs ≥ 20%) against the RS were made using all available data (All-RS pool+HI RS only). Among 218 samples with RS 0-25, 164 (75%) had Ki-67 <20% and 54 (25%) had Ki-67 ≥20%. Among 80 samples with RS 26-100, 57 (71%) had Ki-67 ≥20% and 23 (29%) had Ki-67 <20%. Conclusions: A moderately positive correlation between the Oncotype DX Breast Recurrence Score result and the Ki-67 IHC MIB-1 pharmDx Score in HR+, HER2- node positive EBC was observed in the All-RS pool. These findings are consistent with prior studies.