CanAssist Breast Risk Stratification in Multifocal/Multicentric Breast Cancer: To Test Each Focus or Not?

Context.—: Unlike unifocal early breast cancer, there is a lack of guidelines on prognostic testing in multifocal/multicentric breast cancer (MF/MC BC), which is pivotal in current clinical practice for adjuvant treatment planning. CanAssist Breast (CAB) is a proteomic, artificial intelligence-based prognostic test for evaluating the risk of distant recurrence within 5 years of diagnosis in patients with hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer. Objective.—: To study CAB-based recurrence risk stratification of multiple tumor foci in MF/MC BC and evaluate its usefulness in adjuvant chemotherapy recommendations. Design.—: Retrospective data from 6126 patients with HR+/HER2- early breast cancer who underwent CAB testing between January 2022 and May 2025 were reviewed. Of these, 107 patients with MF/MC BC, on whom the CAB test was performed on more than 1 tumor focus, were further studied, and concordance/discordance in CAB risk categories among multiple foci was evaluated. Results.—: In the MF/MC BC, CAB risk assessment of multiple foci revealed discordance in 18 of 107 patients (17%), demonstrating notable intertumoral heterogeneity. Analysis of a stepwise protocol shows that, among 75 patients, 8 (11%) had a clinically high-risk tumor with CAB-low risk, while the clinically low-risk tumor resulted in CAB-high risk, underscoring the complexity of prognostication in MF/MC BC. Conclusions.—: We recommend a tiered approach of CAB testing in patients with MF/MC BC, whereby, if the first tumor shows CAB-low risk, testing of additional tumor foci is recommended. This approach improves risk stratification and enables tailored adjuvant treatment planning, while minimizing the risk of undertreatment.