Chemotherapy Confers No Survival Benefit in Older Breast Cancer Population

A statistically non-significant absolute difference in OS probability between the chemotherapy and control groups of 1.3% (95% CI, –2.4% to 5.0%) at 4 years and 4.5% (95% CI, –2.1% to 11.1%) at 8 years emerged.

The addition of adjuvant chemotherapy to hormonotherapy did not significantly improve survival in women 70 years and older with genomic grade index (GGI) high-risk estrogen receptor (ER)–positive HER2-negative breast cancer vs hormonotherapy alone, according to results from the phase 3 ASTER 70s trial (NCT01564056) published in The Lancet.

Efficacy data revealed that after a median follow-up of 7.8 years (95% CI, 7.5-7.8), 135 of 541 patients treated with chemotherapy and 144 of 548 who did not receive chemotherapy had died. The 4-year overall survival (OS) in the chemotherapy and control groups were 90.5% (95% CI, 87.6%-92.8%) vs 89.3% (86.2%-91.6%), and the 8-year rates were 72.7% (95% CI, 67.8%-77.0%) vs 68.3% (95% CI, 63.3%-72.7%), respectively (HR, 0.83; 95% CI, 0.63-1.11; P = .2100). A statistically non-significant absolute difference in OS probability of 1.3% (95% CI, –2.4% to 5.0%) at 4 years and 4.5% (95% CI, –2.1% to 11.1%) at 8 years emerged, with no significant validation of the proportional risk assumption (P = .059).

Furthermore, a sensitivity analysis revealed that the restricted mean survival time in the chemotherapy and control arms was 8.8 years (95% CI, 8.6-9.0) vs 8.6 years (8.4-8.9). No significant differences between groups were observed regarding invasive disease-free survival (DFS) or breast cancer-specific survival.

“In this superiority trial, adjuvant chemotherapy did not provide any statistically significant benefit in terms of OS compared with hormonotherapy alone in women aged 70 years or older with GGI high-risk ER–positive HER2-negative breast cancer,” Etienne Brain, MD, a medical oncologist at Institut Curie/Saint-Cloud, wrote in the publication with study coauthors. “We also did not identify any statistically significant differential effect of the addition of chemotherapy in the subgroups studied according to age, G8 frailty score, Lee’s score, GGI high-risk subcategory, tumor size, or nodal status. However, safety and longitudinal analyses of health-related quality of life favored the no chemotherapy group.”

The phase 3 superiority trial was conducted across 84 sites in France and Belgium and enrolled patients 70 years and older who underwent complete surgery for ER–positive HER2-negative primary breast cancer or isolated local relapse. Those enrolled were randomly assigned 1:1 to receive hormonotherapy alone or with chemotherapy, and patients were stratified by frailty, nodal status, and treatment site.

Chemotherapy consisted of 1 of 3 options with 600 mg/m² of cyclophosphamide for four 3-week cycles: 60 mg/m² of doxorubicin, non-pegylated liposomal doxorubicin 60 mg/m², or 75 mg/m² docetaxel. Additionally, radiotherapy was delivered following chemotherapy and prior to hormonotherapy, on a hypofractionated schedule. Hormonotherapy was given as tamoxifen, an aromatase inhibitor, or a combination of both for 5 years.

In the chemotherapy and control groups, the median age was 75.2 years (range, 72.9-79.0) and 74.9 years (72.4-78.6), with 63% vs 69% of patients having an ECOG performance status of 0. A total of 59% vs 61% of the respective arms had a G8 geriatric frailty score of greater than 14, 69% vs 69% had a Lee’s prognostic index score from 6 to 9, and 49% vs 52% had an age-adjusted Charlson comorbidity index of 5. Furthermore, 7% vs 10% had a history of non-breast cancer, 50% vs 50% had a pT stage of 2, 55% vs 55% had a pN stage of 0, and 72% vs 68% had ductal invasive histology.

The primary end point of the trial was OS. Secondary end points included invasive DFS, any second invasive cancer, breast cancer-specific survival, and safety.

Safety data revealed that more adverse effects (AEs) were observed in the chemotherapy group, particularly regarding hematologic, gastrointestinal, skin, or administration site-related AEs or infections. Discontinuation due to toxicity occurred in 7% of patients treated with chemotherapy. Additionally, 3 deaths were reported in the chemotherapy group, due to single instances of peritonitis, cardiac event, and general deterioration; 1 death in the control group occurred due to stroke.

Reference

Brain E, Mir O, Bourbouloux E, et al. 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. Lancet. 2025;406:489-500. doi:10.1016/S0140-6736(25)00832-3