Dr Stein on the Key Clinical Implications of Data from the OPTIMA Trial in ER+, HER2– Early Breast Cancer

“We divided our patients into subgroups, and this is where it gets particularly interesting.… We treated everybody, all premenopausal women, [including those who underwent] ovarian function suppression for 3 years or more, and unlike any of the previous trials, we showed no difference in recurrence risks between the 2 trial arms.”

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 findings from the phase 3 OPTIMA trial (ISRCTN42400492), which was presented during the 2026 ASCO Annual Meeting. In addition to discussing data from the trial and key aspects of its design, Stein explained important clinical implications of the trial.

The trial evaluated adjuvant treatment directed by the 50-gene Prosigna assay vs standard chemotherapy followed by endocrine therapy in patients with high clinical risk estrogen receptor (ER)–positive/HER2-negative early breast cancer. Data from the trial found that in the per-protocol population, patients in the test-directed arm (n = 2094) experienced a 5-year invasive breast cancer–free survival rate of 90.3% (95% CI, 88.5%-91.8%) compared with 91.8% (95% CI, 90.1%-93.2%) in the control arm (n = 2059; adjusted HR, 1.03; 95% CI, 0.85-1.25; P = .006).

Stein noted that like other trials, patients in the study were divided into subgroups. However, he also pointed out how it is common for other trials to reveal mixed results when including patients with ER-positive, HER2-negative disease who are premenopausal. OPTIMA included patients who were premenopausal with an ovarian function suppression history of at least 3 years, and yet there was no statistically significant difference in recurrence risk between the arms, he added. Additionally, patients who had up to 9 involved lymph nodes were included in the trial. Stein concluded by pointing out that positive data with the Prosigna assay in patients who were premenopausal and/or had up to 9 involved lymph nodes may lead changes in clinical practice and guidelines.