Adjuvant chemotherapy and hormonotherapy versus adjuvant hormonotherapy alone for women aged 70 years and older with high-risk breast cancer based on the genomic grade index (ASTER 70s): a randomised phase 3 trial

Brain E, Mir O, Bourbouloux E, et al. Lancet 2025; 406: 489-500.

The ASTER 70s trial was designed to resolve clinical equipoise regarding the utility of adjuvant chemotherapy for women aged 70 years and older with oestrogen receptor-positive (ER+), HER2-negative breast cancer. Patients with tumours found to have high-risk of recurrence determined by the Genomic Grade Index (GGI) were included. This trial directly addressed the underrepresentation of this demographic in similar chemotherapy trials such as MINDACT, TAILORx, and RxPONDER. The primary objective was to definitively assess whether the addition of adjuvant chemotherapy to standard hormonotherapy conferred a benefit in overall survival.  

Participants were recruited from 84 clinical sites across France and Belgium. Following screening, 1,089 patients were randomly allocated on a 1:1 basis to receive either four cycles of a taxane-based or anthracycline-based chemotherapy regimen followed by adjuvant hormonotherapy, or to receive adjuvant hormonotherapy alone. Randomisation was stratified by centre, nodal status (pN+ vs pN0), and frailty status as determined by the G8 screening tool score (≤14 vs >14). The primary endpoint was overall survival, with secondary endpoints including invasive disease-free survival (IDFS) and breast cancer-specific survival (BCSS).  

After a median follow-up of 7.8 years, there was no statistically significant improvement in overall survival with the addition of chemotherapy. The 8-year overall survival rate was 72.7% (95% CI 67.8–77.0) in the chemotherapy group versus 68.3% (95% CI 63.3–72.7) in the hormonotherapy-alone group, yielding a non-significant absolute difference (hazard ratio 0.83, 95% CI 0.63 to 1.11). This lack of benefit was consistent across all secondary efficacy endpoints or within subgroup analysis. The incidence of grade 3 or higher adverse events was significantly higher in the chemotherapy arm, occurring in 183 of 541 patients (34%) compared with 52 of 548 patients (9%) in the control arm. Quality of life data showed a significantly shorter time until definitive deterioration across multiple functional and symptom domains for patients receiving chemotherapy.

In conclusion, the ASTER 70s trial provides evidence that for women aged 70 years and older with genomic high-risk, ER+/HER2- breast cancer, adjuvant chemotherapy confers no survival benefit, whilst resulting in significantly more adverse events and deterioration in quality of life. These results stand in contrast to findings from trials in younger cohorts, such as RxPONDER, and serve as a caution against the extrapolation of treatment paradigms across disparate age demographics. Unfortunately the GGI assay has been discontinued and the authors acknowledge this as a significant limitation. They plan to reanalyse tumour samples using the 21-gene recurrence score. Ultimately, ASTER 70s provides evidence to support the de-escalation of systemic therapy in older women and to guide shared decision-making, favouring the omission of chemotherapy in this specific patient population.

Summary Author: Mr James Bryan, PhD Student, University of Sheffield and Higher Surgical Trainee, Yorkshire and Humber Deanery

Supervisor: Miss Jenna Morgan, NIHR Advanced Fellow, University of Sheffield and Consultant Oncoplastic Breast Surgeon, Doncaster and Bassetlaw Teaching Hospitals