DOI: 10.1200/po-25-01285 ISSN: 2473-4284

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

Joyce O'Shaughnessy, Adam M. Brufsky, Rakhshanda Layeequr Rahman, Cynthia R. Osborne, Reshma Mahtani, Ahmed Elkhanany, Cathy Lynne Graham, Eric Brown, Linsey P. Gold, Nathalie Johnson, Danilo Giffoni, J. Jaime Alberty-Oller, Harshini Ramaswamy, Raquel Weber, Nicole Chmielewski-Stivers, Andrea R. Menicucci, William Audeh
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PURPOSE

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.

MATERIALS AND METHODS

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.

RESULTS

Among patients with H1 cancers (n = 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 = .70). By contrast, patients with H2 cancers (n = 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 = .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 = .036). Clinical and pathologic variables did not predict anthracycline benefit.

CONCLUSION

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.

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