Individuals with estrogen receptor–positive, HER2-negative, high-risk early breast cancer and low Prosigna (PAM50) risk of recurrence (ROR) scores of 60 or less were able to safely skip chemotherapy, according to findings from a randomized, noninferiority phase III trial presented at the 2026 ASCO Annual Meeting (Abstract 500). The Prosigna gene expression test guided treatment for endocrine therapy with or without chemotherapy based on the ROR score.
“OPTIMA addresses a long-standing challenge in breast cancer care: identifying who truly benefits from chemotherapy and who does not. Our findings show that many patients can safely avoid chemotherapy without compromising their outcomes,” said chief investigator Rob Stein, MA, MB BChir, PhD, FRCP, Professor of Breast Oncology at the UCL Cancer Institute, London, United Kingdom. “These results mark an important and significant step toward more personalized treatment. The trial has successfully used tumor biology to guide decisions rather than relying solely on traditional clinical features. For patients, this means many may be spared the physical and emotional burden of chemotherapy and its potential long-term side effects. For health systems, it represents a more efficient and evidence-based use of resources.”
Study Methods
OPTIMA is a randomized, noninferiority phase III trial that enrolled women and men aged 40 years or above who had estrogen receptor–positive, HER2-negative early breast cancer and 0 to 9 involved axillary nodes and T size ≥ 30 mm, if node negative. All patients were recommended to receive chemotherapy.
Patients were randomly assigned to receive standard chemotherapy followed by endocrine therapy or to a Prosigna test, from Veracyte, to direct a decision for the addition of chemotherapy, or not. In the Prosigna arm, patients with tumors that had an ROR score above 60 were assigned to chemotherapy plus endocrine therapy while patients with tumors with lower ROR scores received endocrine therapy alone. Endocrine therapy also included ovarian function suppression for premenopausal women in the absence of chemotherapy-induced ovarian insufficiency.
Patients in the Prosigna arm were blinded to their randomization and ROR scores were not disclosed.
The trial was powered to demonstrate noninferiority of 5-year invasive breast cancer–free survival in the Prosigna arm. The control arm allowed treatment comparison for those who received endocrine therapy alone.
Key Findings
A total of 4,429 patients were randomly assigned in the study. In the test-directed arm (n = 2,214), 68% had low ROR score tumors.
Patients were followed for a median of 3.9 years. During that time, there were 280 events of invasive breast cancer–free survival, 66% of which were distant recurrences.
The 5-year invasive breast cancer–free survival rate was 91.% (95% confidence interval [CI] = 89.7%–92.9%) in the control arm and 90.4% (95% CI = 88.6%–92.0%) in the test-directed arm (hazard ratio [HR] = 0.99; 90% CI = 0.81–1.20; noninferiority P = .013), which met the predefined noninferiority margin.
In the low ROR score group, the 5-year invasive breast cancer–free survival rate was 94.9% (95% CI = 92.9%–96.4%) in the control arm and the rate was 93.7% (95% CI = 91.8%–95.2%) in patients in the test-directed arm (HR = 1.06; 90% CI = 0.78–1.46; noninferiority P = .0051).
No significant differences were noted in outcomes between subgroups.
“OPTIMA provides robust, practice‑changing evidence that we can safely reduce the use of chemotherapy for many patients with hormone‑sensitive breast cancer,” said co-chief investigator Iain MacPherson, MD, PhD, FRCP, Professor of Breast Oncology and Clinical Senior Lecturer in the Institute of Cancer Sciences at the University of Glasgow. “These findings represent a major step forward in delivering more personalized, precise care, ensuring that treatment decisions are driven by what will genuinely improve outcomes for patients, while avoiding unnecessary toxicity. The potential impact for both patients and health services is substantial.”
DISCLOSURES: The University College London sponsored the OPTIMA trial, and the trial was funded by grants from the National Institute for Health and Care Research as well as additional funding and testing support from Veracyte Inc. For full disclosures of the study authors, visit coi.asco.org.
