The largest randomized trial to date examining adjuvant chemotherapy in elderly breast cancer patients has found no survival advantage from adding chemotherapy to hormone therapy, challenging current treatment paradigms for this vulnerable population. The ASTER 70 study, published in Nature Reviews Clinical Oncology, enrolled 1,089 patients aged 70 years and older with completely resected early-stage ER+HER2- breast cancer at high risk of recurrence.
Study Design and Patient Population
ASTER 70 represents the first phase III randomized trial specifically designed to evaluate adjuvant chemotherapy in elderly patients with hormone-sensitive breast cancer. Participants were identified as high-risk based on the Genomic Grade Index (GGI), an 8-gene prognostic classifier, addressing a critical knowledge gap since patients aged 70 and older have been historically under-represented in breast cancer trials.
The study randomly assigned patients to receive either adjuvant taxane-based or anthracycline-based chemotherapy followed by standard hormone therapy, or hormone therapy alone. The primary endpoint was overall survival, with researchers following patients for a median of 7.8 years.
No Survival Benefit Despite High-Risk Classification
Results demonstrated no statistically significant improvement in overall survival with the addition of chemotherapy. At four years, survival rates reached 90.5% in the chemotherapy group compared to 89.3% in patients receiving hormone therapy alone. By eight years, these rates were 72.7% and 68.3%, respectively, with the 4.5 percentage point difference failing to achieve statistical significance.
These findings are particularly notable given that all enrolled patients were classified as high-risk based on genomic profiling, a population typically expected to derive the greatest benefit from chemotherapy.
Significant Toxicity Burden
The study revealed a stark contrast in treatment tolerability between the two approaches. Grade 3 or higher adverse events occurred in 34% of patients treated with chemotherapy compared to only 9% in the hormone therapy-only group. Beyond objective toxicity measures, patients receiving chemotherapy reported substantially worse quality of life, experiencing increased fatigue, pain, digestive disorders, and decreased autonomy.
Clinical Implications for Elderly Care
"The ASTER 70s study marks a turning point in the management of older women with breast cancer," said Professor Etienne Brain, medical oncologist at Institut Curie and principal investigator. "For the first time, a phase III study shows that the addition of chemotherapy does not provide a statistically significant benefit in terms of overall survival, even in patients with high genomic risk."
Brain emphasized that the results highlight the importance of considering not only tumor biology but also patient age, frailty, and individual expectations when making treatment decisions. The findings challenge the practice of extrapolating treatment standards established in younger patients to elderly populations without adequate evidence.
Research Collaboration and Future Directions
The study was designed and coordinated by Unicancer R&D in partnership with Institut Curie teams, involving 84 public and private centers across France and Belgium. The collaborative effort drew on expertise from GERICO and UCBG research groups, specializing in oncogeriatrics and breast cancer respectively.
"ASTER 70s is study that exemplifies Unicancer's leading role in academic research," noted Professor Jean-Yves Blay, president of Unicancer. "It shows that ambitious clinical trials focused on patient needs can answer questions that have remained unanswered for too long."
The research represents a significant step toward more individualized therapeutic approaches that balance treatment benefits against risks specific to elderly populations. As Professor Steven Le Gouill, director of the Hospital Group of Institut Curie, observed, the work demonstrates commitment to personalized oncology that prioritizes quality of life and implements care pathways specifically designed for elderly women.
These findings are expected to influence clinical guidelines and support more nuanced treatment decisions that consider the unique needs and circumstances of elderly breast cancer patients, potentially reducing unnecessary treatments while maintaining optimal outcomes.
