Abstract 3316: Comparative analysis of Ki67 and BCI for risk of recurrence and prediction of extended endocrine therapy benefit in the BCI Registry study

Abstract Background: The BCI Registry study is an ongoing trial with over 3000 enrolled patients diagnosed with HR+ early-stage breast cancer to assess long-term outcomes as well as the overall impact of BCI in treatment decisions. The BCI (H/I) ratio has been validated to predict benefit from extended endocrine therapy (EET) in the MA.17, Trans-aTTom, IDEAL and B-42 trials. The BCI score is prognostic for the risk of distant recurrence. Ki67 is a well-known prognostic marker for invasive breast cancer disease. A high expression of Ki67 relates to a higher proportion of actively dividing cells within the tumor, which is associated with more aggressive behavior and poorer prognosis. Conversely, low Ki67 expression indicates a lower proliferation rate and may be associated with a less aggressive tumor phenotype and better prognosis. This analysis investigates the relationship between BCI (H/I) and BCI score against Ki67 score in patients enrolled in the BCI Registry study. Methods: BCI Registry patients with available BCI and Ki67 results were incorporated in this study (n=1872), consisting of 1483 node negative and 389 node-positive patients. BCI (H/I)-Low and BCI (H/I)-High groups were derived from a pre-specified cut-point. Ki67 score was stratified into the following risk groups: Low risk (Ki67 < 10%), Intermediate risk (Ki67: 10 to 25%), and High risk (Ki67 > 25%). Kendall correlation (R) was used to examine the correlation between BCI (H/I), BCI score and Ki67 score as continuous variables. Descriptive statistics were used to summarize the distribution of BCI (H/I) categories and BCI prognostic groups across all Ki67 risk categories for all patients and subsets based on nodal status. Results: In the overall cohort, 37.2%, 27.2% and 35.6% patients were classified by Ki67 as Low, Intermediate and High Risk, respectively. In addition, 61.5% of patients were classified as BCI (H/I)-Low and 38.5% as BCI (H/I)-High. Continuous analysis of BCI (H/I) versus Ki67 revealed a weak correlation (R= 0.14), but a positive correlation for BCI score versus Ki67 (R= 0.46). Within Ki67 Low Risk patients, 27.4% were classified as BCI (H/I)-High, and 48.1% of Ki67 High Risk patients were classified as BCI (H/I)-Low. The prognostic analysis identified 28.6% of Ki67 Low Risk patients classified as BCI high risk and 17.3% of Ki67 High Risk patients classified as BCI low risk. In addition, 51.8% and 48.2% of Ki67 Intermediate Risk patients were classified as BCI low risk and high risk, respectively. Conclusions: These results confirm only a weak correlation between BCI (H/I) and Ki67 but a moderate correlation between the BCI score and Ki67. These findings further highlight the important distinction between prognostic and predictive biomarkers, where prognostic risk assessment by Ki67 does not predict the likelihood of benefit from extended endocrine therapy. Citation Format: Sami Diab, Natalia Siuliukina, Brandon O’Neal, Amanda K. L. Anderson, Yi Zhang, Kai Treuner. Comparative analysis of Ki67 and BCI for risk of recurrence and prediction of extended endocrine therapy benefit in the BCI Registry study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3316.