Benefit from dose-dense adjuvant chemotherapy for breast cancer: subgroup analyses from the randomised phase 3 PANTHER trialResearch in context

Background: It is unclear whether some patients with high-risk breast cancer do not warrant adjuvant dose-dense chemotherapy due to small expected absolute benefit. Methods: The phase 3 PANTHER trial (NCT00798070) compared adjuvant sequential epirubicin/cyclophosphamide (EC) and docetaxel (D) admini...

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Published in:The Lancet regional health. Europe 2025-02, Vol.49, p.101162
Main Authors: Alexios Matikas, Andri Papakonstantinou, Sibylle Loibl, Günther G. Steger, Michael Untch, Hemming Johansson, Nikos Tsiknakis, Mats Hellström, Richard Greil, Volker Möbus, Michael Gnant, Jonas Bergh, Theodoros Foukakis
Format: Article
Language:English
Subjects:
Adjuvant chemotherapy
Amenorrhea
Breast cancer
Dose-dense
PREDICT
STEPP
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Summary:Background: It is unclear whether some patients with high-risk breast cancer do not warrant adjuvant dose-dense chemotherapy due to small expected absolute benefit. Methods: The phase 3 PANTHER trial (NCT00798070) compared adjuvant sequential epirubicin/cyclophosphamide (EC) and docetaxel (D) administered in either tailored dose-dense (tDD EC/D) or standard interval schedule (FEC/D) to patients with high-risk resected early breast cancer (n = 2003). We compared outcomes across key subgroups of interest, evaluated the performance of the online prognostication and treatment benefit estimation tool PREDICT and conducted a subpopulation treatment effect pattern plot (STEPP) analysis. Primary endpoint was breast cancer recurrence free survival (BCRFS). Findings: Median follow-up was 10.3 years. Treatment with tDD EC/D improved 10-year BCRFS across all subgroups including according to menopausal status, with an absolute benefit of 2% or more, as well as in luminal (Hazard Ratio [HR] = 0.83, 95% Confidence Interval [CI] 0.65–1.05) and Human Epidermal Growth Factor Receptor 2 (HER2) positive (HR = 0.53, 95% CI 0.30–0.93), but not triple negative breast cancer patients (HR = 1.02, 95% CI 0.66–1.57). PREDICT underestimated overall survival in the entire population and across all subgroups. In STEPP analysis, absolute benefit from tDD EC/D in BCRFS was stable across risk-defined subpopulations, from 3.8% in the lowest risk patients to 3.6% in the highest risk ones. There was no differential treatment effect over time. Interpretation: We could not reliably identify any subgroup not benefiting from dose-dense treatment, which should be considered for patients with primary resected high-risk breast cancer. Funding: Cancerfonden, Bröstcancerförbundet, Radiumhemmets Forskningsfonder, Amgen, Roche, sanofi-aventis.
ISSN:2666-7762