Publication: JCO Precis Oncol, June 2026 DOI https://doi.org/10.1200/PO-25-01285

Authors: Joyce O’Shaughnessy et al.

Title: Prognostic Performance of MammaPrint in Patients with Small T1a, b, and c Node-Negative Early Breast Cancer

Abstract

Purpose: Randomized trials have not demonstrated clear benefit from anthracyclines for patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HER22) early breast cancer (EBC). The MammaPrint 70- gene signature, specifically the High-Risk 1 (H1) and High-Risk 2 (H2) subgroups, was evaluated in predicting benefit from anthracycline- and taxane based chemotherapy (AC-T) compared with taxane/cyclophosphamide (TC) in hormone receptor–positive HER22 EBC.

Materials & Methods: This analysis used prospectively collected real-world data from patients enrolled in the FLEX study with stage I-III hormone receptor–positive HER22 EBC, MammaPrint High-Risk, and BluePrint Luminal B tumors who received adjuvant AC-T or TC. Inverse probability of treatment weighting (IPTW) was performed to balance clinical characteristics between treatment groups. The association between the chemotherapy regimen and 3-year invasive disease free survival (IDFS) was assessed using Kaplan-Meier estimates and Cox proportional hazards models.

Results: Among patients with H1 cancers (n 5 1,106), 3-year IDFS did not differ between AC-T and TC (95.9% v 95.9%; adjusted hazard ratio [HRs], 1.14 [95% CI, 0.64 to 2.06]; P 5 .70). By contrast, patients with H2 cancers (n 5 153) demonstrated significantly improved 3-year IDFS with AC-T versus TC (100% v 94.8%; adjusted HRs, 0.10 [95% CI, 0.01 to 0.75]; absolute benefit 5.2%; P 5 .025). A significant treatment-by-MammaPrint interaction demonstrated that AC-T benefit increased with higher genomic risk (adjusted HRs, 0.09 [95% CI, 0.01 to 0.85]; P 5 .036). Clinical and pathologic variables did not predict anthracycline benefit.

Conclusion: An integrated genomic approach that combines BP and ImPrint maximizes prediction of pCR outcome in this dataset, particularly for the HR+/HER2+ subgroup. Further evaluation is warranted, as these data could be useful for guiding clinical decision-making, including selection of chemotherapy backbone and adjuvant therapy. Importantly, this approach may help identify patients who are overtreated or undertreated with current strategies, including those with exceptional treatment sensitivity who may be candidates for chemotherapy de-escalation.