Breast Cancer Index and Recommendations for Extended Endocrine Therapy

Importance The Breast Cancer Index (BCI) is an established genomic assay that provides individualized risks of overall and late distant recurrence and predicts the likelihood of extended endocrine therapy (EET) benefit in patients with early-stage, hormone receptor–positive (HR+) breast cancer. Previous findings from the first 1000 patients in the prospective BCI Registry showed that physicians changed their EET recommendation in more than 40% of patients. Objective To investigate the use of the BCI in the full registry cohort and how physicians integrate prognostic and predictive results in real care settings. Design, Setting, and Participants The BCI Registry study is a US multicenter evaluation of long-term clinical outcome, decision impact, and medication adherence among patients enrolled from April 2021 to January 2024. Participants included women diagnosed with early-stage, HR+ breast cancer. Physician and patient questionnaires about recommendations or preferences for EET and confidence or comfort with these decisions were collected. For this cohort study, data were analyzed from January 2025 to March 2026. Exposure Patients received BCI testing and endocrine therapy. The BCI prognostic model calculated a risk score to classify patients as having low or high risk of late distant recurrence, while the BCI predictive component used the BCI HOXB13/IL17BR (H/I) ratio to classify patients as having low or high likelihood of EET benefit. Main Outcomes and Measures Change in physicians’ and patients’ recommendations or preferences for EET, and their confidence or comfort with these decisions. Pre-BCI and post-BCI results were analyzed using the McNemar test. Fisher exact test was used to determine the association between BCI categories and clinical variables. Results The final analysis included 2900 women with completed physician and patient questionnaires (mean [SD] age, 65.2 [10.3] years). Among these patients, 2570 (88.6%) were postmenopausal, 2245 (77.4%) were N0, and 2501 (86.2%) were HER2-negative. After BCI testing, 1209 physicians (41.7%) changed their EET recommendation ( P < .001), and 1479 patients (51.0%) changed their preference for EET ( P < .001). Among 1100 patients classified as BCI (H/I)–High, EET recommendations increased from 671 pre-BCI (61.0%) to 1014 post-BCI (92.2%). Among 1800 patients classified as BCI (H/I)–Low, the number of physicians not recommending EET increased from 856 (47.6%) to 1576 (87.6%). Physician confidence in their recommendation increased for 1269 patients (43.8%; P < .001), and 1260 patients (43.4%) were more comfortable with the EET decision ( P < .001). Conclusions and Relevance This cohort study of patients from the BCI Registry highlights the important treatment guidance provided by the BCI to reduce EET undertreatment or overtreatment and further substantiates its clinical utility to individualize patient care.