Abstract PO5-01-11: Breast Cancer Index and comparative analysis of late distant recurrence risk with results from the TEAM trial
Authors: Bartlett John MS , Zhang Yi , Pond Gregory , Wong Jenna , Xu Keying , Spears Melanie , Mallon Elizabeth , Taylor Karen , Hasenburg Annette , Markopoulos Christos , Dirix Luc , Seynaeve Caroline , Velde Cornelis J.H. van de , Rea Daniel , Brufsky Adam , Stål Olle , Sgroi Dennis , Schnabel Catherine , Treuner Kai , Bayani Jane 
Published: May 2024

Abstract
Background: Individualized risk assessment of distant recurrence (DR) is critical for early-stage HR+ breast cancer patients, as prolonged risk of recurrence continues even after completing 5 years of adjuvant endocrine therapy. The Breast Cancer Index (BCI) is a guideline-endorsed, validated gene expression assay that provides an individualized risk of overall (0-10y) and late (5-10y) DR and predicts the likelihood of benefit from extended endocrine therapy. The current BCI assay reports prognostic risk estimates based on tamoxifen-treated patients from the Stockholm (STO-3) cohort for node-negative (N0) patients, enrolled between 1976 through 1990 and a retrospective cohort from Massachusetts General Hospital (MGH) for patients with 1 to 3 positive nodes (N1), diagnosed between 1993 and 2007, of which approximately 50% were tamoxifen-treated. More recently, additional validation was completed in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial, in which patients were enrolled between 2001 and 2006. Here, individualized DR risk estimates from the TEAM trial were compared with those from Stockholm and MGH cohorts.
Methods: For the TEAM translational study, BCI testing was performed blinded to clinical outcome and BCI and BCIN+ risk scores were calculated as previously described. A total of 2910 postmenopausal patients with HR+ breast cancer, including 1285 N0 and 1625 N1 patients, who remained DR-free for five years were analyzed to determine the risk of late DR. Cox proportional hazard models using Breslow estimates were used to calculate the risk of late DR as a function of continuous BCI risk scores.
Results: Late DR risk estimates from both the TEAM trial and the Stockholm/MGH cohorts are summarized in the table below. In N0 patients, comparison of 5-10y risk estimates of late DR observed in TEAM patients were higher than those in the Stockholm cohort for BCI scores less than 8.0, but reduced for BCI scores greater than 8.0. Risk estimates differed by 1.5% for a BCI score of 0 and -4.3% for a BCI score of 10. A similar pattern was observed for N1 patients between the TEAM and MGH cohorts, with risk estimates from TEAM trial being higher for BCI scores less than 8.0 but reduced for BCI scores greater than 8.0 compared to those from the MGH cohort.
Conclusions: BCI prognostic validation in the TEAM trial enabled the characterization of DR risk that is more compatible with the current standard of care in the US, as postmenopausal patients were all treated with at least 2-3 years or 5 years of primary adjuvant endocrine therapy with an aromatase inhibitor. Results from the TEAM study provide a more representative assessment of late DR risk to guide individualized treatment decision-making for HR+ early-stage breast cancer patients.
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Citation Format: John MS Bartlett, Yi Zhang, Gregory Pond, Jenna Wong, Keying Xu, Melanie Spears, Elizabeth Mallon, Karen Taylor, Annette Hasenburg, Christos Markopoulos, Luc Dirix, Caroline Seynaeve, Cornelis J.H. van de Velde, Daniel Rea, Adam Brufsky, Olle Stål, Dennis Sgroi, Catherine Schnabel, Kai Treuner, Jane Bayani. Breast Cancer Index and comparative analysis of late distant recurrence risk with results from the TEAM trial [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 PO5-01-11.