Abstract PO1-02-03: Correlative analysis of Breast Cancer Index with CTS5 for prediction of extended endocrine benefit in the BCI Registry study

Abstract Background Hormone receptor-positive (HR+) breast cancer patients face a prolonged risk of late distant recurrence even after 5 years of primary adjuvant endocrine therapy and derive only a modest benefit from extended endocrine therapy (EET). The Breast Cancer Index (BCI) is a validated genomic assay that provides the risk of late (post 5 years) and overall (0-10 years) distant recurrence and predicts EET benefit in patients with HR+ disease. The predictive component of BCI, HOXB13/IL17BR ratio BCI (H/I), stratifies patients as Low- and High-Likelihood to benefit from EET and has been validated in the MA.17, Trans-aTTom, IDEAL, and B-42 trials. The Clinical Treatment Score post-5 years (CTS5) is a prognostic tool incorporating standard clinical risk factors such as age at diagnosis, tumor size, tumor grade, and nodal involvement to inform prognosis of late distant recurrence. A previous analysis in the IDEAL trial showed that CTS5 was not predictive of EET benefit. Here, we examine the relationship between BCI (H/I) and CTS5 in a large cohort from the BCI Registry study. Methods The BCI Registry study is an ongoing prospective study to evaluate 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. BCI (H/I)-Low and BCI (H/I)-High groups were determined using pre-specified cut-points. CTS5 scores were calculated using clinical information from the ClinCapture electronic data capture system and stratified into Low-, Intermediate-, and High-risk groups using published cut-points. Pearson’s correlation coefficient (r) was used to estimate the correlation between BCI (H/I) and CTS5 as continuous variables. Descriptive statistics were used to summarize the distribution of BCI (H/I) groups across all CTS5 risk categories. Results BCI and CTS5 results were reported for 1520 patients (75.1% T1; 53.4% grade II; 80.3% N0). BCI (H/I) classified 934 patients (61.4%) as BCI (H/I)-Low and 586 patients (38.6%) as BCI (H/I)-High. BCI Prognostic classified 705 patients (46.4%) as BCI-Low risk for late distant recurrence and 815 patients (53.6%) as BCI-High risk. CTS5 classified 945 patients (62.2%) as CST5-Low, 400 patients (26.3%) as CTS5-Intermediate, and 175 patients (11.5%) as CTS5-High. When analyzed as continuous variables, BCI (H/I) showed a weak correlation with CTS5 (r=0.18). When stratifying CTS5 risk categories by BCI (H/I) groups, 65.2% (N=616) of CTS5-Low patients were classified as BCI (H/I)-Low, while 34.8% (N=329) of CTS5-High Low patients were classified as BCI (H/I)-High. In addition, 57.8% (N=231) and 42.2% (N=169) of CTS5-Intermediate patients were classified as BCI (H/I)-Low and BCI (H/I)-High, respectively. Finally, 49.7% (N=87) and 50.3% (N=88) of CTS5-High patients were classified as BCI (H/I)-Low and BCI (H/I)-High, respectively. Conclusion BCI (H/I) consistently stratified CTS5 risk categories into separate BCI (H/I)-Low and BCI (H/I)-High groups, indicating that risk prognostication does not equate to prediction of benefit from EET. These results confirm previous findings in the IDEAL study demonstrating that CTS5 is not predictive of EET benefit and further substantiate the clinical utility of BCI as the only predictive biomarker for extended endocrine therapy benefit in patients with HR+ early-stage breast cancer. Citation Format: Naomi Dempsey, Jenna Wong, Natalia Siuliukina, Yi Zhang, Kai Treuner, Reshma Mahtani. Correlative analysis of Breast Cancer Index with CTS5 for prediction of extended endocrine benefit in the BCI Registry study abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-02-03.