Prediction of Anthracycline Benefit in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early-Stage Breast Cancer by the MammaPrint 70-Gene Signature for Patients Enrolled in the FLEX Study.

Abstract

Randomized trials have not demonstrated clear benefit from anthracyclines for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2-) 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 HER2- EBC. This analysis used prospectively collected real-world data from patients enrolled in the FLEX study with stage I-III hormone receptor-positive HER2- 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. Among patients with H1 cancers (n = 1,106), 3-year IDFS did not differ between AC-T and TC (95.9% <i>v</i> 95.9%; adjusted hazard ratio [HRs], 1.14 [95% CI, 0.64 to 2.06]; <i>P</i> = .70). By contrast, patients with H2 cancers (n = 153) demonstrated significantly improved 3-year IDFS with AC-T versus TC (100% <i>v</i> 94.8%; adjusted HRs, 0.10 [95% CI, 0.01 to 0.75]; absolute benefit 5.2%; <i>P</i> = .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]; <i>P</i> = .036). Clinical and pathologic variables did not predict anthracycline benefit. Patients with MammaPrint H2 tumors had a clinically meaningful benefit from anthracycline-containing chemotherapy, whereas patients with H1 tumors did not derive more benefit from AC-T than from TC despite overlapping high-risk features. These findings support the use of MammaPrint to inform chemotherapy regimen selection and warrant further validation.