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

Sep 22, 2026

Upload by Ben

The analysis evaluates whether the MammaPrint 70-gene signature, focusing on High-Risk 1 (H1) and High-Risk 2 (H2) subgroups, predicts benefit from anthracycline-and taxane-based chemotherapy (AC-T) versus taxane/cyclophosphamide (TC) in hormone receptor–positive, HER2-negative early breast cancer. Using prospectively collected real-world FLEX study data with inverse probability of treatment weighting, it assesses 3-year invasive disease-free survival via Kaplan–Meier and Cox models.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Purpose

Materials and Methods

Results

Conclusion

Introduction

Context

Key Objective

Knowledge Generated

Relevance

Original Reports | Cancer Genomics 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, MD1; Adam M. Brufsky, MD, PhD2 ; Rakhshanda Layeequr Rahman, MD3; Cynthia R. Osborne, MD4; Reshma Mahtani, DO5 ; Ahmed Elkhanany, MD6 ; Cathy Lynne Graham, MD7 ; Eric Brown, MD8; Linsey P. Gold, MD8; Nathalie Johnson, MD9; Danilo Giffoni, MD10 ; J. Jaime Alberty-Oller, MD11 ; Harshini Ramaswamy, MS12; Raquel Weber, PhD12 ; Nicole Chmielewski-Stivers, PhD12 ; Andrea R. Menicucci, PhD12 ; and William Audeh, MD, MS12 DOI [https://doi.org/10.1200/PO-25-01285](https://doi.org/10.1200/PO-25-01285) | 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 taxanebased chemotherapy (AC-T) compared with taxane/cyclophosphamide (TC) in hormone receptor–positive HER2 2 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 2 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 diseasefree 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) . Asigniﬁcant 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 | 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. | ACCOMPANYING CONTENT Appendix Data Sharing Statement Accepted May 15, 2026 Published June 24, 2026 JCO Precis Oncol 10:e2501285 © 2026 by American Society of Clinical Oncology Creative Commons Attribution Non-Commercial No Derivatives 4.0 License INTRODUCTION Anthracyclines are among the most effective antitumor agents used in the treatment of breast cancer. Meta-analyses from the Early Breast Cancer (EBC) Trialists’ Collaborative Group (EBCTCG) have demonstrated that chemotherapy regimens incorporating an anthracycline substantially reduce recurrence risk and improve survival compared with nonanthracycline regimens.1 For patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HER22) EBC, both anthracycline-containing regimens, such as doxorubicin/cyclophosphamide followed by paclitaxel (AC-T), and nonanthracycline regimens, such as docetaxel/cyclophosphamide (TC), remain standards of care. However, limited data exist to guide identiﬁcation of patients who beneﬁt from anthracycline [ascopubs.org/journal/po](ascopubs.org/journal/po |

FAQs

What clinical question does the MammaPrint assay address in this analysis?

It examines whether recurrence risk from the MammaPrint assay can identify patients with hormone receptor–positive, HER2-negative early breast cancer who benefit from anthracycline-containing chemotherapy.

How were treatment groups balanced in the FLEX real-world analysis?

Inverse probability of treatment weighting (IPTW) was used to balance clinical characteristics between patients receiving AC-T and those receiving TC.

What were the main outcome findings for the H1 and H2 MammaPrint subgroups?

Patients with H1 cancers showed no difference in 3-year invasive disease-free survival between AC-T and TC, while H2 cancers had significantly improved 3-year IDFS with AC-T versus TC.

Sep 22, 2026

Upload by Ben