Prediction of benefit from docetaxel chemotherapy for HR-positive breast cancer in the PACS-01 trial

Sep 22, 2026

Adjuvant chemotherapy for hormone receptor–positive (HR+) breast cancer often uses taxanes, yet existing tests cannot clearly identify which patients benefit. This study evaluates whether the SETER/PR index, reflecting endocrinerelated transcriptional activity, predicts benefit from docetaxel in node-positive HR+ patients in the PACS-01 trial. SETER/PR and Recurrence Score (RS) were measured in 490 patients and analyzed against distant recurrence-free interval (DRFI) using Cox models with interaction terms. Results showed significant treatment interactions for continuous SETER/PR, with high SETER/PR (≥1.50) indicating worse outcomes with 3FEC+3D versus 6FEC.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Article information

Background

Patients and methods

Results

Conclusion

Trial registration

Keywords

Introduction

The Breast 89 (2026) 104894 Contents lists available at ScienceDirect The Breast journal [homepage:](homepage: www.journals.elsevier.com/the-breast)[ www.journals.elsevier.com/the-breast](homepage: www.journals.elsevier.com/the-breast) | Prediction of benefit from docetaxel chemotherapy for HR-positive breast cancer in the PACS-01 trial | | | | --- | --- | --- | | Fr´ed´erique Penault-Llorcaa,* , Amelie Lusque b , Thomas Filleron b , Kevin Tranc, Lili Duc , Rick Baehnerd,e, Florence Dalenc f, Magali Lacroix-Triki g, Thomas Bacheloth, Fabrice Andrei, Pascal Boucher j , J´erˆome Lemonnierj , W. Fraser Symmansc
a Department of Biopathology, Centre Jean Perrin, Universit´e Clermont Auvergne, INSERM, U1240 Imagerie Mol´eculaire et Strat´egies Th´eranostiques, Clermont Ferrand, F-63000, France
b Biostatistics & Health Data Science Unit, University of Toulouse, Oncopole Claudius Regaud, IUCT-Oncopole, Toulouse, France c Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA d Exact Sciences, Madison, WI, USA
e Department of Pathology, University of California, San Francisco, CA, USA
f Department of Medical Oncology, Oncopole Claudius Regaud, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France g Department of Pathology, Institut Gustave Roussy, Villejuif, France
h Department of Medical Oncology, Centre Leon Berard, Lyon, France i Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France j Unicancer, Paris, France | | | | A R T I C L E I N F O | A B S T R A C T
Background: Adjuvant chemotherapy for hormone receptor–positive (HR+) breast cancer relies on taxanes, but existing tests do not identify which patients benefit from them. The SETER/PR index, a measure of endocrinerelated transcriptional activity in HR + tumors, recently predicted benefit from paclitaxel when low (<0.75), but not for anthracycline-based therapy. We tested whether SET ER/PR could predict benefit from docetaxel in node-positive, HR + patients enrolled in the PACS-01 trial (docetaxel after fluorouracil–epirubicin–cyclophosphamide (3FEC+3D) versus 6FEC).
Patients and methods: SET ER/PR index and Recurrence Score (RS) were obtained for 490 patients. SET ER/PR was quantified using the QuantiGene Plex assay from RNA remaining after RS testing. Pre-specified analyses assessed SET ER/PR as a continuous variable and using the predefined <0.75 cut point, as well as continuous RS and the >25 cut point. The primary endpoint was distant recurrence-free interval (DRFI). Predictive value was assessed using Cox models including biomarker, treatment arm, and interaction term.
Results: Continuous SET ER/PR demonstrated significant interaction with treatment on DRFI (P interaction = 0.028), whereas predefined <0.75 cut point was not predictive (P interaction = 0.668). Exploratory analyses identified a cut point at 1.50 (P interaction = 0.013): patients with SET ER/PR ≥ 1.50 had worse outcomes with 3FEC+3D versus 6FEC (HR 3.16, 95%CI 1.28–7.85), while outcomes were similar between arms when SET ER/PR < 1.50 (HR 0.83, 95%CI 0.51–1.35). RS did not predict differential benefit, either continuously (P interaction = 0.670) or at the >25 threshold (P interaction = 0.534).
Conclusion: Including sequential docetaxel (3FEC+3D) was less effective than continued anthracycline chemotherapy (6FEC) when breast cancer had high endocrine-related transcriptional activity (i.e., SET ER/PR index ≥1.50).
Trial registration: PACS-01. | | | Presentations: Results from this study werepresented in part at the San Antonio Breast Cancer Symposium December 2025, in San Antonio, TX. | | | | Keywords: Docetaxel Anthracycline Chemotherapy Prediction Hormone receptor SET
Index Recurrence score Menopausal Breast cancer Endocrine Transcription Activity | | | * Corresponding author. Centre Jean Perrin, Universit´e Clermont Auvergne, INSERM, U1240 Imagerie Mol´eculaire et Stra

FAQs

What was the main goal of the PACS-01 trial analysis in this study?

To test whether the SETER/PR index could predict benefit from docetaxel chemotherapy in node-positive HR+ breast cancer patients enrolled in PACS-01.

How were SETER/PR and Recurrence Score (RS) measured?

SETER/PR was quantified using the QuantiGene Plex assay from RNA remaining after RS testing, and RS values were obtained for the 490 patients.

Did RS predict differential benefit between chemotherapy arms?

No. RS did not show predictive differential benefit either as a continuous variable or using the >25 threshold, based on non-significant interaction P values.

When did docetaxel-containing treatment (3FEC+3D) perform worse?

Exploratory analyses found that patients with SETER/PR ≥ 1.50 had worse outcomes with 3FEC+3D compared with continued anthracycline chemotherapy (6FEC).

Sep 22, 2026

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