Role of neoadjuvant versus adjuvant chemotherapy, dose density, and treatment schedule in biologically high-risk HR+/HER2- breast cancer: A pooled analysis of the WSG ADAPT-HR+/HER2- and PlanB trials.

Author(s): Sherko Kuemmel; Ulrike Nitz; Michael Wilhelm Braun; Kerstin Luedtke-Heckenkamp; Maren Darsow; Helmut Forstbauer; Bahriye Aktas; Eva-Maria Grischke; Claudia Schumacher; Toralf Reimer; Wolfram Malter; Benno Nuding; Rachel Wuerstlein; Matthias Christgen; Hans Heinrich Kreipe; Ronald E. Kates; Christine zu Eulenburg; Rick Baehner; Nadia Harbeck;

Source: DOI: 10.1200/JCO.2026.44.17

Dr. Maen Hussein's Thoughts

1467 pts with RS > 25 and 551 with clinically (neoadjuvant cohort in ADAPT-HR+/HER2-) or pathologically N2, (longer) docetaxel-based CTx showed better distant, invasive disease-free survival in N2-3 pts patients with RS ≤25, OS was also shown in pts with RS>25 anthracycline regimens did not show a significant survival difference in high-risk HR+/HER2 whether used in neoadjuvant or adjuvant setting. So may be no anthracycline for HR+ve pts who are high risk disease.

BACKGROUND

Dose-dense anthracycline-taxane chemotherapy (CTx) is standard for high-risk early breast cancer (eBC) and is often given in the neoadjuvant setting if CTx is clearly indicated (e.g., recurrence score, RS > 25 and/or > 4 positive lymph nodes by imaging) or if downstaging is needed. While dose-dense CTx improves outcomes irrespective of hormone receptor (HR) status in meta-analyses, its benefit in node-negative HR+ eBC appears limited. Further meta-analyses on neoadjuvant vs adjuvant use, and on mono- vs combined therapy, showed mixed results. These findings highlight an unmet need for a refined treatment selection, informed by the assessment of relative survival benefit. We therefore pooled the WSG ADAPT-HR+/HER2- and PlanB trials to estimate the impact of dose density, anthracycline use, and treatment setting on survival.

METHODS

Invasive (iDFS), distant disease-free survival (dDFS), and overall survival (OS) were analyzed retrospectively in a pooled analysis of HR+/HER2- patients (pts) in ADAPT-HR+/HER2- (n = 2331) and PlanB (n = 2220) who received chemotherapy and had follow-up data (data cut: Jan 26, 2026). In ADAPT-HR+/HER2-, pts high-risk received 8× weekly nab-paclitaxel vs. 4× biweekly sb-paclitaxel, followed by epirubicin + cyclophosphamide (EC) in either the neoadjuvant or adjuvant setting. PlanB randomized pts intermediate- to high-risk to adjuvant 4× EC followed by 4× docetaxel (EC-T) vs. 6× TC. To minimize bias, predefined uniform cross-trial subgroups (RS > 25 any pN; pN2–3 any RS) were considered here, and propensity scoring for non-random allocations (neoadjuvant vs adjuvant CTx in ADAPT-HR+/HER2-, physician choice).

RESULTS

This pooled analysis included 1467 pts with RS > 25 and 551 with clinically (neoadjuvant cohort in ADAPT-HR+/HER2-) or pathologically N2-3 eBC. Dose-dense anthracycline or paclitaxel yielded inferior iDFS and dDFS than q3w docetaxel, even after adjustment for cT, age, and grade. This effect, favoring a (longer) docetaxel-based CTx, was present among N2-3 pts with RS ≤25, who showed better iDFS, dDFS, and OS, and among RS > 25 pts (in particular, in N0-1), who showed better dDFS. Informed by these results, we assessed the impact of anthracyclines in PlanB pts with RS > 25 and/or N2-3 and observed no significant survival differences. There was no significant survival difference between neoadjuvant vs adjuvant CTx in the corresponding subset of ADAPT-HR+/HER2- pts, even in propensity-scored analysis.

CONCLUSIONS

Our exploratory retrospective analysis does not show a significant survival difference by anthracycline use or treatment setting (neoadjuvant vs adjuvant) in high-risk HR+/HER2- eBC pts who are candidates for CTx. Optimal use of dose-dense CTx in the context of docetaxel-based treatment requires further investigation.

CLINICAL TRIAL INFORMATION

NCT01779206; NCT01049425. This is an ASCO Meeting Abstract from the 2026 ASCO Annual Meeting II. This abstract does not include a full text component.

Author Affiliations

¹West German Study Group and Ev. Hospital Bethesda, Breast Center Niederrhein, Moenchengladbach, Germany and University Hospital Cologne, Cologne, Germany; ²Breast Unit, Kliniken Essen-Mitte, Essen, Germany and Department of Gynecology with Breast Center, Charité – Universitätsmedizin Berlin, Berlin, Germany; ³West German Study Group, Moenchengladbach, Germany; ⁴Interdisciplinary Breast Center, Rotkreuz-Clinics Munich, Munich, Germany; ⁵Department of Oncology and Hematology, Niels-Stensen-Kliniken, Georgsmarienhütte, Germany; ⁶Luisenhospital Duesseldorf, Practice for Senologic Oncology, Duesseldorf, Germany; ⁷Practice Network Hematology/Oncology, Troisdorf, Germany; ⁸Department of Gynecology, University Hospital Leipzig, Leipzig, Germany; ⁹University Women´s Clinic Tuebingen, Eberhard Karls University, Tubingen, Germany; ¹⁰St. Elisabeth-Krankenhaus, Köln, Germany; ¹¹Universitätsklinikum Rostock, Rostock, Germany; ¹²Women’s Clinic and Breast Center, University Clinics Cologne, Cologne, Germany; ¹³EVK Bergisch Gladbach, Bergoisch Gladbach, Germany; ¹⁴West German Study Group, Moenchengladbach, Germany and Breast Center, Department of Obstetrics & Gynecology, University of Munich (LMU) and CCCLMU, Munich, Germany; ¹⁵Hannover Medical School, Institute of Pathology, Hannover, Germany; ¹⁶REK Consulting, West German Study Group, Otterfing, Germany; ¹⁷Exact Sciences Corporation, Madison, WI; ¹⁸Breast Center, Department of OB&GYN, and Munich Comprehensive Cancer Center (CCC LMU), LMU University of Munich, Munich, Germany

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