The use of adjuvant chemotherapy in older women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer has been continuously debated. Despite being the most common breast cancer subtype in women aged 70 years or more, clinical decision-making has historically relied on evidence generated from younger cohorts, where the benefits of chemotherapy are more pronounced.1,2
Results from the phase 3 ASTER 70s trial (NCT01564056), recently published in The Lancet, shed critical light on this issue, suggesting that chemotherapy may offer limited survival benefit in this population while substantially increasing toxicity risks.1,2
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The ASTER 70s trial enrolled over 1000 women aged 70 or older with newly diagnosed HR-positive, HER2-negative early breast cancer or isolated recurrence. All tumor specimens were assessed with the Genomic Grade Index (GGI), an 8-gene test used to classify risk. Patients with high-risk disease were randomized to receive adjuvant chemotherapy followed by endocrine therapy or solely endocrine therapy. The median age of the participants was 75 years, and around 40% had a score of 14 or less on the G8 frailty test, indicating common health issues in this group.2
After a median follow-up of 7.8 years, no statistically significant survival benefit was observed for chemotherapy. At 4 years, overall survival (OS) was 90.5% in the chemotherapy-endocrine group versus 89.3% with sole endocrine therapy. At 8 years, OS was 72.7% versus 68.3%, neither reaching statistical significance (HR, 0.83; 95% CI, 0.63–1.11; P = 0.21).¹ These findings challenge the routine use of adjuvant chemotherapy in older patients with genomically high-risk HR-positive disease.
Severe adverse effects were seen in 34% of the patients receiving chemotherapy, compared with only 9% in those who received endocrine treatment. Treatment-related deaths occurred only in the chemotherapy group and none in the endocrine-only group.¹ Such toxicity has extreme implications for older patients, since many also face risks of mortality from other non-cancer health issues.
These results highlight the importance of weighing quality of life against modest, if any, survival gains with chemotherapy. As noted by Sabine Linn, MD, and Florentine Hilbers, MD, in an editorial, the study aimed to detect a large survival improvement but lacked sensitivity to capture smaller subgroup effects; this highlights why careful analysis, and not just a broad restriction on chemotherapy, is necessary for older adults.1
While providing key insights, the ASTER 70s study had notable flaws. The team used a non-commercial genomic assay, which may reduce how much providers can apply this data in day-to-day clinic operations where tests like Oncotype DX and MammaPrint are more commonly applied. Additionally, competing mortality in older populations diluted the trial’s ability to measure modest benefits from chemotherapy. Finally, subgroup analyses by frailty, age strata, or comorbidity were underpowered, leaving uncertainty about whether specific subsets of older patients could still benefit.²,³
The ASTER 70s study provides strong evidence that adjuvant chemotherapy offers minimal survival benefit but significant toxicity in older women with high-risk HR-positive, HER2-negative breast cancer. While these facts don’t fully rule out benefit for select subgroups, they highlight the need for tailored care plans, gene risk assessment, and patient-centered care. Pharmacists play a key role in these conversations, aiding both patients and providers in balancing efficacy with tolerability in this vulnerable population.