Effect of dose-dense adjuvant chemotherapy in patients with node-positive early breast cancer according to estrogen receptor levels: an exploratory analysis of the GIM2 trial
In brief
Dose-dense chemotherapy benefited node-positive breast cancer across estrogen receptor levels
In an exploratory analysis of 1,709 patients followed for a median of 15 years, dose-dense chemotherapy showed a consistent benefit across estrogen receptor levels. Receptor expression was linked to long-term outcomes but did not identify who benefited more from the dose-dense schedule; small numbers with receptor-negative or low-expression tumors limit certainty.
- Journal
- Breast (Edinburgh, Scotland) (Q1)
- Published
- 29 September 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Carmine De Angelis, Alessandra Rosa, Virginia Delucchi, Francesca Poggio, Mario Giuliano, Michelino De Laurentiis, et al.
- PMID
- 42826677
- DOI
- 10.1016/j.breast.2026.104942
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 4 October 2026): Dose‑dense chemo analysis, systemic therapy relevance
Abstract
BACKGROUND: Estrogen receptor (ER)-negative early breast cancer (eBC) generally derives greater benefit from adjuvant chemotherapy than ER-positive disease, but the predictive role of ER expression levels for dose-dense (DD) chemotherapy remains uncertain. This exploratory analysis of the GIM2 phase III trial evaluated whether ER expression influences the efficacy of DD chemotherapy in node-positive eBC. METHODS: In the GIM2 trial, patients with node-positive eBC were randomized to receive anthracycline-based chemotherapy followed by paclitaxel, administered either in a DD or standard-interval schedule. ER expression was categorized as ER 0, ER-low (1-10%), ER-intermediate (11-50%), and ER-high (>50%). Associations between ER levels and invasive disease-free survival (iDFS) and overall survival (OS) were evaluated using multivariable Cox models. Treatment effects across the continuum of ER expression were explored using STEPP. RESULTS: Among 1709 eligible patients, 150 (9%) had ER 0, 78 (4%) ER-low, 283 (17%) ER-intermediate, and 1198 (70%) ER-high tumors. After a median follow-up of 15 years (IQR 8-16), 15-year iDFS rates were 48%, 59%, 56%, and 59%, respectively (p = 0.001). Corresponding 15-year OS rates were 72%, 71%, 68%, and 75% (p < 0.001). ER expression was independently associated with both iDFS and OS; however, no significant interaction was observed between ER levels and treatment effect for either endpoint. STEPP analyses demonstrated a consistent benefit of DD chemotherapy across the spectrum of ER expression. CONCLUSIONS: ER expression levels were prognostic, but quantitative ER expression did not identify a subgroup with a clearly differential benefit from DD chemotherapy. Given the exploratory nature of this analysis and the small size of the ER-0 and ER-low subgroups, these hypothesis-generating findings are consistent with DD chemotherapy remaining an effective adjuvant treatment option for patients with node-positive eBC across the range of ER expression.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.