Dr Stein on Test-Directed Chemotherapy in ER+, HER2– Early Breast Cancer

“We found is that there weas no difference, either in the full analysis population or in the patients with low ROR score tumors, [which] was consistent with our predefined noninferiority hypothesis. In the full population the P-value was .006 and in the low-score population [it was] .003.”

Robert Stein, MBBS, PhD, an honorary consultant oncologist at University College London (UCL) Hospitals and a professor of breast oncology at UCL Cancer Institute, discussed data from the phase 3 OPTIMA trial (ISRCTN42400492) that were presented during the 2026 ASCO Annual Meeting.

OPTIMA compared chemotherapy treatment decisions made with the Prosigna (PAM50) gene expression test with standard treatment in patients with estrogen receptor–positive, HER2-negative early breast cancer. The analysis compared outcomes in both the overall study population and a subgroup of patients with tumors classified as having a low Risk of Recurrence (ROR) score, Stein said. Across both groups, no significant differences in recurrence rates were observed between the treatment strategies being compared, supporting the study’s predefined hypothesis that the experimental approach would be noninferior to the standard treatment, he added.

The statistical analysis demonstrated that the noninferiority end point was met in both populations, Stein said. In the overall study cohort, the comparison yielded a highly significant result supporting noninferiority, and a similar finding was observed among patients with low-ROR tumors, he noted. These results indicate that omitting chemotherapy did not lead to clinically meaningful increases in the risk of recurrence for these patients, he explained.

The findings can also be interpreted from a clinical perspective using the study’s predefined noninferiority margin. Even under the most conservative assumptions, the maximum potential benefit of chemotherapy was estimated to be no greater than an absolute reduction in recurrence risk of approximately 2%, Stein explained.

This modest potential benefit must be weighed against the certainty that all patients who receive chemotherapy will be exposed to its associated toxicities, Stein underscored. Although only a small proportion of patients might derive a reduction in recurrence risk, every patient undergoing treatment would experience the burden of chemotherapy, including short-term adverse effects and the possibility of long-term complications, he concluded.