Perioperative chemotherapy remains a cornerstone of treatment for patients with high-risk HR-positive/HER2-negative early breast cancer. Among the commonly used regimens, dose-dense anthracycline-taxane chemotherapy has long been considered a standard option. However, important clinical questions remain regarding the optimal timing of chemotherapy, patient selection, regimen composition, and treatment intensity.At the 2026 ASCO Annual Meeting, the West German Study Group (WSG) presented a retrospective pooled analysis of two landmark clinical trials—ADAPT-HR+/HER2− and PlanB (Abstract LBA515). The study systematically evaluated how treatment timing, anthracycline use, neoadjuvant endocrine therapy, and chemotherapy dose density influence long-term survival in patients with high-risk HR+/HER2− early breast cancer.
To explore the relevance of these findings for Chinese clinical practice, Oncology Frontier invited Dr. Hao Yu from Zhongshan Hospital Affiliated to Dalian University to review the key results of the pooled analysis, while Professor Jia Wang, also from Zhongshan Hospital Affiliated to Dalian University, provides expert commentary on how these data may inform individualized treatment strategies for Chinese patients.
Expert Commentary
One of the greatest challenges in luminal breast cancer—defined as ER- and/or PR-positive, HER2-negative disease—is determining how to individualize chemotherapy appropriately. On one hand, efforts have focused on safely sparing chemotherapy in patients with low tumor burden and low recurrence risk, as exemplified by the WSG’s ADAPT series. On the other hand, patients with high-risk disease require carefully optimized chemotherapy, raising several important clinical questions.
These include whether patients with heavy tumor burden or high genomic recurrence scores should undergo surgery first or receive neoadjuvant therapy; whether neoadjuvant treatment should consist of chemotherapy or endocrine therapy; whether neoadjuvant endocrine therapy influences the efficacy of subsequent chemotherapy; and finally, which chemotherapy regimen—including the role of anthracyclines, taxanes, and dose density—provides the greatest benefit.
The retrospective pooled analysis presented at this year’s ASCO addressed many of these issues. Among patients with ER/PR-positive, HER2-negative disease and either a Recurrence Score (RS) >25 or clinical/pathological N2–3 nodal involvement, neoadjuvant chemotherapy achieved survival outcomes comparable to those of adjuvant chemotherapy. Although retrospective, the analysis offers valuable insights for clinical decision-making.
First, regarding the timing of systemic treatment, the study suggests that choosing neoadjuvant chemotherapy rather than surgery first does not significantly affect long-term survival in high-risk HR-positive disease. Since primary surgery provides the most accurate assessment of nodal status and complete pathological information, it may actually facilitate more precise postoperative systemic treatment planning. Consequently, for patients with operable luminal breast cancer and substantial tumor burden, an upfront surgical approach may often be preferable.
Second, the study provides important information regarding chemotherapy regimen selection. No overall survival advantage was observed with anthracycline-containing regimens, a finding that is consistent with previous studies. Given the well-recognized risks of cardiotoxicity, secondary leukemia, and cumulative toxicity associated with anthracyclines, clinicians should carefully balance potential benefits against these long-term risks.
Equally noteworthy is the comparison between different taxane schedules. A regimen based on docetaxel administered every three weeks, with a total treatment duration of 18–24 weeks, produced significantly better invasive disease-free survival than a shorter, dose-dense anthracycline plus taxane regimen. These findings suggest that, in luminal breast cancer, the pace of chemotherapy may be more important than its intensity. Extending treatment duration rather than compressing treatment cycles may represent the more effective strategy.
Third, multigene assays remain essential tools for treatment decision-making in this patient population. However, most currently available genomic assays were developed and validated primarily in Western populations. There is therefore an urgent need for large, multicenter studies in Chinese patients to establish population-specific genomic risk models and scoring systems.
Finally, retrospective analyses continue to play an important role in clinical research. They challenge long-held assumptions, identify heterogeneous responses among high-risk subgroups, and generate hypotheses for future prospective studies. In this case, the pooled analysis raises important questions regarding the routine use of dose-dense chemotherapy while offering new perspectives on optimizing treatment strategies for high-risk HR-positive breast cancer.
Study Summary
Background
Following the landmark TAILORx and RxPONDER trials, treatment of HR-positive/HER2-negative early breast cancer has entered the era of precision medicine, allowing many patients with low-risk disease to safely avoid chemotherapy. For patients at higher risk—particularly those with a Recurrence Score (RS) greater than 25 or clinical/pathological N2–3 nodal involvement—chemotherapy remains an essential component of treatment.
Current guidelines generally recommend dose-dense anthracycline-taxane regimens for these patients, and neoadjuvant therapy is frequently considered. However, evidence supporting the superiority of anthracycline-containing regimens over anthracycline-free docetaxel-based regimens has remained inconsistent, with meaningful benefit largely confined to patients with extensive nodal disease. Likewise, previous studies comparing dose-dense versus conventional chemotherapy schedules, as well as neoadjuvant versus adjuvant chemotherapy, have produced conflicting results.
To address these questions, investigators from the West German Study Group (WSG) performed a retrospective pooled analysis combining patient-level data from the ADAPT-HR+/HER2− and PlanB trials.
Methods
The analysis included HR-positive/HER2-negative patients from the PlanB (n=2,220) and ADAPT-HR+/HER2− (n=2,331) trials who received chemotherapy and had available follow-up data. To minimize bias, investigators predefined a common high-risk population consisting of patients with RS >25 and/or clinical or pathological N2–3 disease.
Because the choice between neoadjuvant and adjuvant chemotherapy in ADAPT-HR+/HER2− was determined by treating physicians rather than randomization, propensity-score adjustment was used to reduce selection bias. A total of 1,910 patients were ultimately included.
Within ADAPT-HR+/HER2−, high-risk patients received either weekly nab-paclitaxel or dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide, administered either before or after surgery. In PlanB, intermediate- and high-risk patients were randomized to receive either four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel or six cycles of docetaxel plus cyclophosphamide. The primary endpoints were invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival.
Results
Among the 1,910 high-risk patients included in the analysis, 82.9% had an RS greater than 25, while 28.8% had clinical or pathological N2–3 disease.
Neoadjuvant endocrine therapy showed no significant impact on invasive disease-free survival. Within the ADAPT-HR+/HER2− trial, 799 patients received endocrine induction therapy before systemic treatment, but survival outcomes were virtually identical to those of patients who did not receive endocrine induction (HR 1.01; P=0.959).
Similarly, the timing of chemotherapy did not influence prognosis. After propensity-score adjustment, no significant differences were observed between neoadjuvant and adjuvant chemotherapy with respect to invasive disease-free survival (HR 1.10; P=0.493), distant disease-free survival, or overall survival.
The use of anthracyclines likewise failed to produce an overall survival advantage. After adjustment for stage, age, and tumor grade, anthracycline-containing regimens did not significantly improve invasive disease-free survival (HR 1.30; P=0.128), although previous pooled analyses from PlanB and SUCCESS C had suggested a possible benefit among patients with N2–3 disease.
The most striking finding concerned chemotherapy regimen selection. Docetaxel administered every three weeks, with a total treatment duration of 18–24 weeks, achieved significantly better invasive disease-free survival than the shorter 16-week dose-dense anthracycline plus (nab-)paclitaxel regimen (adjusted HR 1.39; P=0.014). A similar trend was observed for distant disease-free survival.
Among patients with RS ≤25 but N2–3 nodal disease, this advantage became even more pronounced. The hazard ratio for invasive disease-free survival reached 2.47 (P=0.015), while distant disease-free survival and overall survival showed similar favorable trends.
Conclusion
This exploratory pooled analysis of the ADAPT-HR+/HER2− and PlanB trials suggests that, among patients with high-risk HR-positive/HER2-negative early breast cancer, the choice between neoadjuvant and adjuvant chemotherapy does not significantly influence survival. Likewise, neither anthracycline use nor endocrine induction therapy conferred a significant survival advantage.
More importantly, chemotherapy regimens based on docetaxel administered every three weeks, whether combined with epirubicin/cyclophosphamide or not, appeared to outperform shorter dose-dense anthracycline-taxane regimens. These findings suggest that future optimization of chemotherapy for high-risk luminal breast cancer should focus less on increasing treatment intensity and more on selecting the appropriate regimen, taxane strategy, and treatment schedule. Prospective studies will be needed to validate these observations in the context of contemporary endocrine therapies.
