Abstract PD1-09: Associations between the 21-gene Oncotype DX Recurrence Score (RS), Ki67, and Race in Early Breast Cancer (EBC) Using the National Cancer Database (NCDB)
Authors: Patel Rima , Kwon Deukwoo , Van Hyfte Grace , Sparano Joseph , Tiersten Amy 
Published: March 2023

Background: The 21-gene RS (Oncotype DX) is a validated genomic signature that provides prognostic information for distant recurrence risk and is predictive of adjuvant chemotherapy benefit in patients with hormone receptor (HR)-positive, HER2-negative early breast cancer (EBC). Ki67 protein expression is a proliferation marker that is determined by immunohistochemistry (IHC) and is a prognostic biomarker in HR-positive EBC. Black race is associated with poorer prognosis in patients with EBC. RS, Ki67 and race have not been evaluated together and the impact of race on the association between Ki67 and RS is unknown. The goal of this study was to evaluate the association between the 21-gene RS and Ki67 based on race in patients with HR-positive EBC using the NCDB.

Methods: Women with HR-positive EBC with 0-3 involved lymph nodes, diagnosed between 2018 and 2019, who had available information on RS, IHC-measured Ki67, and race in the NCDB dataset were identified. Patients were stratified by RS of low (0-10), intermediate (11-25) and high (26-100) and categorized into Ki67 low (/=30%) based on the International Ki67 Working Group prognostic classification (PMID: 33369635). Wilcoxon rank test was used to test for continuous variables and chi-square test was used for categorical variables. Agreement between Ki67 and RS was estimated using Fleiss Kappa statistic and corresponding p-value was reported.

Results: 43,898 eligible women were included. 17.43% were lymph node positive. 78% were Non-Hispanic White, 7.98% Non-Hispanic Black, 6.42% Hispanic, and 4.26% Asian American/Pacific Islander (AAPI). The table below describes the distribution of Ki67 and RS in the overall population and racial subgroups. The distribution of Ki67 scores was significantly different between races with a higher proportion of Black patients having high Ki67 scores, p&lt; 0.0001. RS distribution varied as well with a greater percentage of high RS in the Black group, p&lt; 0.0001. There was only slight agreement (Kappa 0.01-0.20) between Ki67 and RS in the overall population (Kappa=0.1929, p&lt; 0.0001), low Ki67 subgroup (Kappa=0.069, p&lt; 0.0001) and intermediate group (Kappa=0.066, p&lt; 0.0001). However, there was fair agreement (Kappa 0.21-0.40) between high Ki67 and RS (Kappa=0.351, p&lt; 0.0001). Based on race as a covariate, in the overall population, agreement between Ki67 and RS remained slight for White, Hispanic, and AAPI groups but was fair for Black patients (Kappa=0.2345, p&lt; 0.0001). In the low Ki67 and intermediate Ki67 groups, agreement remained slight across all races, p&lt; 0.0001. While there was fair agreement between high Ki67 and RS in all racial subgroups, agreement between high Ki67 and RS was highest in the Black subgroup (Kappa=0.392, p&lt; 0.0001) followed by the AAPI (Kappa=0.363, p&lt; 0.0001), White (Kappa=0.342, p&lt; 0.0001) and Hispanic (Kappa=0.339, p&lt; 0.0001) groups.

Conclusions: In this large patient population from the NCDB, there was only slight agreement between Ki67 and RS in the overall, low Ki67, and intermediate Ki67 groups but fair agreement in the high Ki67 group. Agreement between high Ki67 and RS was greatest in the Black subgroup compared to other races. This may be attributed to the higher proportion of patients with high Ki67 and RS in the Black subgroup. Future analyses on overall survival will determine the impact of race on the prognostic value of Ki67 and RS.

Table 1. Distribution of Ki67 and RS by Racial/Ethnic Subgroup AAPI: Asian American/Pacific Islander AIAN: American Indian and Alaska Native

Citation Format: Rima Patel, Deukwoo Kwon, Grace Van Hyfte, Joseph Sparano, Amy Tiersten. Associations between the 21-gene Oncotype DX Recurrence Score (RS), Ki67, and Race in Early Breast Cancer (EBC) Using the National Cancer Database (NCDB) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD1-09.