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.

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LBA515 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 at 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 at 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 .

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