MammaPrint H2 (70-gene signature) flags anthracycline benefit in HR+/HER2− early breast cancer

MammaPrint is a 70-gene prognostic signature; in FLEX real-world, prospectively collected data, the investigators asked whether its High-Risk 1 (H1) vs High-Risk 2 (H2) subgroups predict incremental benefit from anthracycline/taxane adjuvant chemotherapy (AC-T) versus anthracycline-free docetaxel/cyclophosphamide (TC) in stage I–III HR+/HER2− early breast cancer with MammaPrint High-Risk and BluePrint Luminal B tumors (IPTW-adjusted). In H1 (n=1,106), 3-year IDFS was identical with AC-T vs TC (95.9% vs 95.9%; adjusted HR 1.14, 95% CI 0.64–2.06; p=0.70), while H2 (n=153) favored AC-T (3-year IDFS 100% vs 94.8%; adjusted HR 0.10, 95% CI 0.01–0.75; p=0.025; absolute +5.2%). This is directionally consistent with prior randomized evidence that anthracycline/taxane regimens can yield modest IDFS gains over TC in higher-risk HER2− disease overall (e.g., ABC trials 4-year IDFS 90.7% vs 88.2%; HR 1.23 for TC vs TaxAC—i.e., TaxAC better), but FLEX suggests the “who benefits” signal may sit in the genomically highest-risk MammaPrint H2 slice rather than the broader High-Risk pool.