Professor Rob Stein

More than two-thirds of patients with high-risk, hormone-sensitive breast cancer could potentially avoid chemotherapy without compromising treatment outcomes, new study findings suggest.

Data from the phase 3 OPTIMA trial, presented at ASCO 2026, showed that a 50-gene test can be used to safely determine which patients can be treated with hormone therapy alone, and that these patients do not experience inferior outcomes as a result.

The Prosigna test identifies whether the breast cancer is luminal A, luminal B, HER2-enriched or basal-like, and combines this molecular information with clinical factors to generate a risk of recurrence (ROR) score.

The trial assessed the test in 4,429 people aged over 40 years with high clinical risk, ER-positive, HER2-negative early breast cancer who had up to nine positive lymph nodes or a tumour size of at least 30 mm, at sites in the UK, Norway, Sweden, Australia, New Zealand and Thailand.

Participants were randomly assigned to standard chemotherapy followed by endocrine therapy (CET) or to a group in whom further treatment was determined by the ROR score.

Patients with a high ROR score (above 60) were assigned CET while those with a low score (below 60) received endocrine therapy alone.

Radiotherapy and other treatments were administered as usual in both study groups.

Headline study findings showed that:

• among the entire study cohort, 68% had a low test score;
• the five-year invasive breast cancer-free survival (IBCFS) was similar between the two groups, at 91.5% for the control and 90.4% for the test arms (hazard ratio (HR) 0.99, non-inferiority p = 0.013); and
• corresponding five-year IBCFS rates for the low test score population were 94.9% in the control and 93.7% in the test groups (HR 1.06; non-inferiority p = 0.0051).

The results indicate that chemotherapy provides little or no benefit to patients with low scores, with researchers estimating that around 5,000 NHS patients a year could avoid chemotherapy as a result of these findings.

“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,” noted chief trial investigator Professor Rob Stein, Professor of Breast Oncology at the UCL Cancer Institute.

“These results mark an important and significant step toward more personalised treatment. The trial has successfully used tumour 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,” he said.

Click here to read the study abstract.