Abstract PS3-07-24: Breast Cancer Index re-stratifies 21-gene assay risk groups for risk of recurrence and extended endocrine therapy benefit: Final Analysis of the BCI Registry Study

Abstract Background Patients with hormone receptor-positive (HR+) early-stage breast cancer face a prolonged risk of recurrence even after adjuvant endocrine therapy. The Breast Cancer Index (BCI) is a genomic classifier that provides the risk of overall (0-10y) and late (post 5 years) distant recurrence (DR) and predicts the likelihood of benefit from extended endocrine therapy (EET) based on the H/I (HOXB13/IL-17BR) ratio. The 21-gene assay (Recurrence Score; OncotypeDX) provides the 9-year risk of DR and the benefit from adjuvant chemotherapy (CT) in HR+/HER2− breast cancer. Here, we investigated the concordance between BCI score and H/I ratio versus RS in HR+/HER2- patients from the full cohort of the BCI Registry study. Methods The BCI Registry study is a prospective, multi-institutional study that enrolled over 3400 patients to determine the long-term clinical outcome, decision impact and medication adherence in HR+ early-stage breast cancer patients receiving BCI testing as part of routine clinical care. Based on TAILORx and RxPONDER results, RS stratified patients into four risk groups: Age ≤ 50, No CT benefit (RS ≤ 15); Age ≤ 50, CT benefit (RS >15); Age > 50, No CT benefit (RS≤25); and Age > 50, CT benefit (RS >25). Kendall’s correlation coefficient (R) was used to estimate the correlation between BCI score, H/I ratio and RS as continuous variables. Cohen’s kappa was used to measure the agreement between H/I and RS categories. Results BCI and RS results were reported for 1238 patients (76% T1; 58% grade II; 84% N0). The H/I ratio classified 834 patients (67%) as H/I-Low and 404 (33%) as H/I-High, respectively, while BCI stratified 649 patients (52%) as low-risk and 589 (48%) as high-risk for late DR. RS classified 45 patients (4%) as Age ≤ 50, No CT benefit, 54 (4%) as Age ≤ 50, CT benefit, 976 (79%) as Age > 50, No CT benefit and 163 (13%) as Age > 50, CT benefit. When analyzed as continuous variables, the BCI score and H/I ratio showed a weak correlation with RS with R=0.2 and R=0.18, respectively. Based on categorical groups, H/I had low concordance with RS for younger women (Age ≤ 50, Cohen’s kappa=0.08, p=0.29) but showed some correlation with RS for older women (Age > 50, Cohen’s kappa=0.21, p<0.001). Among those older than Age 50, the H/I ratio identified 29% of those with no predicted CT benefit as likely to benefit from EET while 39% of those with predicted CT benefit as not likely to benefit from EET. Table 1. Cross-tabulation of RS and H/I groups Conclusion This comparative analysis between BCI and the 21-gene assay revealed a low concordance between the BCI score and H/I ratio with RS risk categories. The H/I ratio consistently re-stratified RS risk categories into distinct H/I-Low and -High groups, confirming that prediction of CT benefit does not equate to prediction of EET benefit. Citation Format: V. Chuy, N. Siuliukina, B. O'Neal, A. K. Anderson, K. Koskins, Y. K. Zhang, K. Treuner, V. K. Gadi. Breast Cancer Index re-stratifies 21-gene assay risk groups for risk of recurrence and extended endocrine therapy benefit: Final Analysis of the BCI Registry Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-07-24.