Combined adjuvant chemotherapy and hormonotherapy did not significantly improve survival outcomes among older patients with high-risk breast cancer compared to hormonotherapy alone, according to phase 3 study results published in The Lancet. 

In addition, the chemotherapy/hormonotherapy platform was associated with excess adverse events.

The adjuvant standard of care for patients aged 70 years or older with estrogen receptor-positive, HER2-negative breast cancer is hormonotherapy. Whether older patients with more aggressive tumors require additional adjuvant treatment remains controversial.

Etienne Brain, MD, medical oncologist at Institut Curie, Paris, and colleagues sought to determine whether adjuvant chemotherapy plus hormonotherapy was more beneficial than hormonotherapy alone in older patients whose tumors were considered high risk using the genomic grade index assay.

Following definitive surgery, patients aged 70 years or older were randomly assigned to four cycles of taxane- or anthracycline-based chemotherapy or to no chemotherapy, followed by hormonotherapy. Overall survival (OS) served as the study’s primary endpoint.

The ASTER 70s study included data of 1089 patients recruited from treatment centers in France and Belgium. The median age was 75.1 years, and 40% of participants were considered fragile under the Geriatric 8 health status screening tool. In total, 541 patients were assigned to chemotherapy plus hormonotherapy and 548 patients were assigned to hormonotherapy alone.

Median follow-up was 7.8 years. When comparing chemotherapy plus hormonotherapy to hormonotherapy alone, the researchers observed similar OS rates at 4 years and at 8 years. The survival difference did not reach statistical significance at either timepoint.

The researchers reported no differences in invasive disease-free survival or breast cancer-specific survival, both key secondary endpoints of the study. Comorbidities were the leading cause of mortality in both groups, followed by breast cancer and second cancers.

Patients assigned to chemotherapy plus hormonotherapy had higher rates of adverse events than those assigned to hormonotherapy alone. The researchers observed at least one grade 3 or higher adverse event in 34% of the chemotherapy/hormonotherapy group compared to 9% of the hormonotherapy group.

“Although the statistically negative results of the ASTER 70s superiority trial do not exclude the possibility that a smaller beneficial effect of chemotherapy might exist and that a subgroup of patients in this selected high-risk older population might benefit from the addition of chemotherapy to hormonotherapy, this trial provides important data to inform the shared decision making between doctor and patient when discussing adjuvant treatment in this age group.”

- Etienne Brain, MD, medical oncologist at Institut Curie, Paris

“An important limitation of this study is its ambitious design. The study was powered based on an assumed overall survival [hazard ratio] of 0.61 in favor of chemotherapy.

While this assumption might be scientifically achievable in an optimal setting, in the ASTER 70s study a large proportion of the randomly allocated older adult population died of a comorbidity during follow-up. These deaths could not have been prevented by chemotherapy.

[This] comprehensive dataset will assist older women in balancing quantity and quality of life when considering chemotherapy to treat their high-risk, estrogen receptor-positive, HER2-negative early breast cancer.”

- Sabine C. Linn, MD, PhD, and Florentine S. Hilbers, MD, MSc, both of University Medical Centre Utrecht, Netherlands, wrote in a related editorial.

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By Cameron Kelsall

References: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00832-3/abstract; https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01233-4/abstract

Disclosures: Brain declared financial ties to drugmakers. See full article for details. Linn declared financial ties to drugmakers. Hilbers declared no financial ties to drugmakers.

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