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.

Document Type

Article

Publication Date

6-2026

Publication Title

JCO Precis Oncol

Abstract

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%

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.

Volume

10

Issue

6

First Page

e2501285

Last Page

e2501285

DOI

10.1200/PO-25-01285

ISSN

2473-4284

PubMed ID

42341255

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