A genomic test may help identify which patients with hormone receptor-positive, HER2-negative early breast cancer are most likely to benefit from anthracycline-containing chemotherapy, potentially allowing others to avoid unnecessary treatment-related toxicity.
Researchers analyzed prospectively collected real-world data from 1,259 patients enrolled in the FLEX registry who had stage I–III disease. Eligibility required a high-risk result on the MammaPrint 70-gene assay, and a Luminal B tumor profile on the BluePrint 80-gene molecular subtyping test. Patients received either an anthracycline- and taxane-based regimen or a taxane/cyclophosphamide regimen after surgery.
The key finding was that the high-risk category was not uniform. Patients classified as High Risk 2 experienced better invasive disease-free survival with anthracycline-containing treatment, while those classified as High Risk 1 achieved similar outcomes regardless of whether anthracyclines were included. Standard clinical features, including tumor size, lymph node involvement and tumor grade, did not distinguish patients who benefited from anthracyclines.
The study, published in JCO Precision Oncology, highlights an emerging role for genomic assays beyond estimating recurrence risk. Corresponding author William Audeh, Chief Medical Officer of Agendia, said, “This study answers a question that randomized clinical trials have been unable to resolve, illustrating the value of genomic profiling to predict benefit from a specific cancer therapy. The FLEX Study highlights the power of a multi-modal, real-world evidence database to produce robust, clinically relevant data which not only inform treatment decisions, but also change clinical practice guidelines.”
The findings also reinforce the growing importance of integrated molecular diagnostics. In this study, patient selection combined results from both the MammaPrint genomic risk assay and the BluePrint molecular subtype classification, illustrating how multiple genomic tests can contribute to increasingly personalized treatment decisions.
The results suggest that genomic classification may help clinicians balance the potential benefits of anthracyclines against their recognized risks, including cardiac toxicity and treatment-related blood disorders. If validated in further studies, testing could support more confident decisions both to recommend anthracyclines for patients most likely to benefit and to avoid exposing others to additional toxicity without improving outcomes.
The authors note that the analysis was based on an observational registry with a median follow-up of just over three years, although statistical methods were used to reduce treatment-selection bias. They conclude that additional validation, including analyses of data from randomized clinical trials, will be needed before the approach is adopted more widely in clinical practice.
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