News|Articles|May 30, 2026

Patients with High-Risk Breast Cancer May Safely Skip Chemo, Trial Finds

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Key Takeaways

Prosigna identified a large high-clinical-risk subgroup with minimal chemotherapy benefit, estimated to avert at most two recurrences per 100 patients treated.
Enrollment broadened prior assay use by including stage 3A tumors and up to nine involved lymph nodes, historically managed with routine chemotherapy.
Five-year IBCFS was 91.2% with standard care versus 89.9% with test-directed omission, remaining within the 2% non-inferiority boundary.
DRFI at five years was 94.1% versus 93.3%, supporting limited incremental metastatic risk reduction from chemotherapy in low-ROR patients.
Generalizability is constrained by exclusion of women <40, predominantly White participation, and a time-driven analysis with 63% under five-year follow-up.

OPTIMA trial data at ASCO 2026 shows a 50-gene test helps patients with high-risk breast cancer avoid unnecessary and toxic chemotherapy treatments.

A landmark clinical trial presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting suggests that approximately two-thirds of patients with high-risk, early-stage breast cancer may safely skip chemotherapy without significantly compromising their long-term outcomes.

The results of the OPTIMA phase 3 trial offer a potential paradigm shift for patients with estrogen receptor (ER)-positive, HER2-negative breast cancer who have traditionally been treated with aggressive chemotherapy due to high clinical risk factors. By using a 50-gene expression assay known as the Prosigna test, researchers found they could identify a large population that derives minimal, if any, benefit from the toxic treatment.

"OPTIMA has demonstrated that the Prosigna test identifies a patient group with minimal if any chemotherapy benefit," the researchers noted in their conclusion, adding that for these patients, chemotherapy prevents at most two recurrences for every 100 patients treated.

Expanding the scope of care

While gene expression assays are already widely used to guide treatment for postmenopausal patients with limited lymph node involvement, the OPTIMA trial pushed these boundaries further. The study included patients with up to nine involved lymph nodes and those with stage 3A tumors, groups that have historically been directed toward chemotherapy regardless of molecular profiles.

Furthermore, the trial provided critical data for premenopausal women aged 40 and older . The results indicate that if these patients are treated with ovarian function suppression, the 50-gene test can safely assist in making adjuvant chemotherapy decisions. This is a significant development, as supporting evidence for gene tests in younger, premenopausal populations has previously been mixed.

Understanding the data

The trial randomized 4,429 patients between January 2017 and December 2025 into either a standard-of-care control arm or a test-directed arm. In the test-directed arm, patients with a "low" Risk of Recurrence (ROR) score (defined as 60 or below) were assigned to receive endocrine therapy alone, skipping chemotherapy.

The primary goal was to prove "non-inferiority," meaning the test-directed approach would not be significantly worse than standard chemotherapy. At the five-year mark, the Invasive Breast Cancer Free Survival (IBCFS) rate was 91.2% for the control group and 89.9% for the test-directed group. While there was a 1.5% difference favoring the group that received chemotherapy, the results fell within the trial’s pre-defined 2% non-inferiority limit.

For Distant Recurrence Free Interval (DRFI), the five-year rates were nearly identical: 94.1% for the control arm and 93.3% for the test-directed arm, a difference of only 0.8%.

Limitations and future directions

Despite the promising results, the researchers acknowledged certain limitations. The study population was predominantly White, though researchers stated it was representative of the participating countries. Additionally, women under the age of 40 were excluded from the trial, meaning these results may not apply to the very youngest patients with breast cancer.

The trial was a "time-driven analysis," with 63% of patients having less than five years of follow-up at the time of this presentation. However, the investigators noted that most chemotherapy benefits regarding recurrence are typically observed within the first five years.

Ongoing analyses are expected to further clarify the cost-effectiveness of implementing this testing strategy on a wider scale. For now, the OPTIMA results provide a new level of reassurance for thousands of patients who may now be able to avoid the life-altering side effects of chemotherapy while maintaining high survival rates.

Reference

“First results from the OPTIMA phase III randomized non-inferiority trial of test-directed chemotherapy in patients with high clinical risk ER-positive HER2-negative early breast cancer” by Dr. Robert C. Stein et al., presented at the 2026 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2026; Chicago, IL.

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