Veracyte’s Prosigna Test Shows Practice-Changing Results in Early Breast Cancer at ASCO 2026 OPTIMA Trial
Veracyte, Inc., a leading cancer diagnostics company, has announced highly significant results from the independent OPTIMA (Optimal Personalised Treatment of early breast cancer using Multi-parameter Analysis) Phase III clinical trial, led by researchers at University College London (UCL). The findings, which will be presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrate that the Prosigna® Breast Cancer Risk of Recurrence (ROR) test can safely guide adjuvant chemotherapy decisions in patients with early-stage, estrogen receptor-positive (ER+), HER2-negative breast cancer.
The study provides strong prospective evidence that many patients traditionally classified as high-risk based on clinical features alone may safely avoid chemotherapy when genomic risk assessment is incorporated into treatment decision-making.
A Major Step Toward Personalized Breast Cancer Treatment
The OPTIMA trial represents one of the most comprehensive efforts to evaluate whether genomic testing can safely reduce unnecessary chemotherapy in early breast cancer. Conducted as a Phase III prospective, randomized controlled study, OPTIMA compared two treatment strategies in patients with ER-positive, HER2-negative early breast cancer:
One group received standard care consisting of chemotherapy followed by hormone therapy, while the other group received treatment guided by the Prosigna test. Patients with high ROR scores (>60) received chemotherapy plus hormone therapy, whereas those with low ROR scores (≤60) were treated with hormone therapy alone, omitting chemotherapy entirely.
The goal of the study was to determine whether genomic profiling could safely identify patients who do not benefit meaningfully from chemotherapy, thereby sparing them from unnecessary toxicity without compromising cancer outcomes.
Key Finding: Many Patients Can Safely Avoid Chemotherapy
One of the most impactful findings from the OPTIMA trial is that chemotherapy can be safely avoided in a substantial proportion of patients who would traditionally be recommended for it based on clinical risk factors alone.
The Prosigna test identified that 68% of clinically high-risk, node-positive patients could safely forgo chemotherapy. These patients achieved a 5-year cancer-free survival rate of 93.7%, which was statistically non-inferior to the 94.9% observed in patients who received chemotherapy.
This result is highly significant because it demonstrates that for many patients, omitting chemotherapy does not increase the risk of recurrence or reduce long-term survival outcomes.
Instead, the findings suggest that tumor biology, as measured through genomic profiling, may be a more accurate predictor of treatment benefit than traditional clinical factors such as tumor size, lymph node involvement, or patient age.
Strong Evidence Across High-Risk Patient Subgroups
The OPTIMA trial also demonstrated consistent results across several high-risk patient subgroups, including populations where treatment decisions have historically been uncertain.
Non-inferiority was confirmed in premenopausal women receiving ovarian function suppression, with a hazard ratio of 1.04 (90% CI 0.60–1.80), indicating no meaningful difference in outcomes between treatment strategies.
Similarly, patients with extensive nodal involvement (classified as pN2 disease with 4–9 positive lymph nodes) also showed comparable outcomes between the genomic-guided approach and standard chemotherapy-based treatment, with a hazard ratio of 1.19 (90% CI 0.62–2.29).
These findings are particularly important because such patients are often considered high-risk and routinely recommended for chemotherapy. The OPTIMA data suggest that genomic risk assessment may allow for more refined and individualized treatment decisions even in these traditionally aggressive disease categories.
High-Quality Prospective Evidence Supporting De-escalation
With 4,429 patients enrolled and a median follow-up period of 4.0 years, the OPTIMA trial represents one of the largest and most robust prospective studies evaluating genomic-guided chemotherapy decisions in early breast cancer.
The study provides Level 1A evidence supporting the clinical utility of the Prosigna test in guiding adjuvant treatment decisions. This level of evidence is considered the highest standard in clinical research and indicates that the findings are based on a well-designed randomized controlled trial with strong statistical validity.
Importantly, the results support the concept of treatment de-escalation, meaning that certain patients can safely receive less intensive therapy without compromising their long-term outcomes.
The Burden of Chemotherapy and the Need for Better Decision Tools
Breast cancer is the most commonly diagnosed cancer globally, affecting approximately one in eight women in the United States alone. Each year, more than 225,000 new cases of hormone receptor-positive, HER2-negative breast cancer are diagnosed.
For many patients, chemotherapy decisions have traditionally been based on clinical characteristics such as tumor size, grade, and lymph node involvement. However, these factors do not always accurately predict which patients will benefit from chemotherapy.
As a result, many patients may be exposed to chemotherapy even when the absolute benefit is limited. This is particularly important given the well-documented side effects associated with chemotherapy, which can significantly impact long-term quality of life.
Studies have shown that up to 43% of breast cancer survivors experience persistent nerve damage following chemotherapy, along with a range of other long-term toxicities that may include fatigue, cognitive impairment, and cardiovascular effects. These side effects highlight the importance of ensuring that chemotherapy is used only when truly necessary.
How the Prosigna Test Works
The Prosigna Breast Cancer Risk of Recurrence (ROR) test is a genomic assay that evaluates tumor biology using a combination of intrinsic subtype classification and gene expression related to tumor proliferation, integrated with clinical-pathological factors.
The test generates a Risk of Recurrence score that helps clinicians determine the likelihood of cancer returning after initial treatment. In the OPTIMA trial, an ROR score of less than 60 was used to identify patients who could safely omit chemotherapy and receive hormone therapy alone.
This approach allows clinicians to move beyond traditional clinicopathological risk assessment and incorporate molecular-level information into treatment planning.
Transformational Impact on Clinical Decision-Making
Experts involved in the study believe the OPTIMA trial results could fundamentally change how early breast cancer is treated in clinical practice.
Professor Robert Stein of University College London, the lead investigator of the study, emphasized that chemotherapy decisions have historically been one of the most challenging aspects of breast cancer care. Patients often ask whether chemotherapy is truly necessary, given its potential side effects.
According to Stein, the OPTIMA trial provides robust evidence that genomic testing can confidently identify patients who do not need chemotherapy, even among those previously considered high risk. He described the findings as potentially practice-changing, highlighting that clinicians can now rely on biological tumor profiling rather than clinical features alone to guide treatment decisions.
Strong Clinical Confidence in De-escalation Strategy
Veracyte leadership also emphasized the significance of the OPTIMA results in strengthening confidence in treatment de-escalation strategies.
Dr. Phillip Febbo, Chief Scientific and Medical Officer at Veracyte, stated that the Prosigna test now has the strongest prospective evidence of any genomic assay in predicting which patients with high-risk, hormone receptor-positive breast cancer can safely avoid chemotherapy.
He noted that this advancement provides dual benefits: for patients, it reduces exposure to unnecessary treatment and its associated side effects; and for clinicians, it offers a validated and reliable tool to support more personalized treatment planning.
ASCO 2026 Presentation and Scientific Recognition
The OPTIMA trial results are being presented at the 2026 ASCO Annual Meeting in a dedicated Breast Cancer—Local/Regional/Adjuvant Oral Abstract Session. The presentation is scheduled for May 30 at 1:15 PM CDT in Hall B1 under Abstract 500.
Professor Robert C. Stein will deliver the oral presentation, and the session will also be available via ASCO’s live-streaming platform, reflecting the high level of interest in the findings within the oncology community.
Implications for the Future of Breast Cancer Care
The OPTIMA trial represents a major advancement in the ongoing shift toward precision oncology in breast cancer treatment. By integrating genomic risk assessment into clinical decision-making, the Prosigna test enables a more individualized approach that balances treatment effectiveness with quality of life.
If adopted widely, these findings could lead to a substantial reduction in unnecessary chemotherapy use among early-stage breast cancer patients, while maintaining excellent long-term outcomes.
This would not only improve patient quality of life by reducing exposure to toxic therapies but also optimize healthcare resources by ensuring that chemotherapy is reserved for those most likely to benefit.
The OPTIMA trial results presented by Veracyte at ASCO 2026 provide compelling evidence that genomic testing using the Prosigna Breast Cancer Risk of Recurrence score can safely guide chemotherapy decisions in early-stage ER-positive, HER2-negative breast cancer.
By demonstrating that a majority of clinically high-risk patients can avoid chemotherapy without compromising survival outcomes, the study represents a significant step forward in personalized cancer treatment.
As oncology continues to evolve toward precision medicine, the OPTIMA findings may help reshape standard clinical practice and support a more targeted, patient-centered approach to breast cancer care.
About the OPTIMA Trial
OPTIMA (Optimal Personalised Treatment of early breast cancer using Multi-parameter Analysis) is an international, multicenter randomized controlled trial led by University College London and funded by U.K. National Institute for Health and Care Research. The independent study enrolled 4,429 women and men aged ≥40 years with ER-positive HER2-negative early breast cancer and 0–9 involved axillary lymph nodes. Participants were randomly assigned to either the control arm for standard chemotherapy followed by hormone therapy or to the Prosigna test-directed arm of standard chemotherapy followed by hormone therapy for patients with Prosigna high ROR test results (>60), versus hormone therapy alone for patients with Prosigna low ROR test results (≤60). All premenopausal women were required to have ovarian function suppression.
About Veracyte
Veracyte (Nasdaq: VCYT) is a global diagnostics company with a vision to transform cancer care for patients around the world. The company’s molecular tests assess the unique biology of each patient’s tumor to help clinicians answer essential questions about cancer care. Veracyte’s Diagnostics Platform combines broad genomic and clinical data, advanced bioinformatics and AI, and a powerful evidence-generation engine to support continued innovation and pipeline development. The company’s portfolio includes the Afirma® Genomic Sequencing Classifier test, Decipher® Bladder Genomic Classifier test, Decipher® Prostate Genomic Classifier test, Prosigna® Breast Risk of Recurrence test, and the TrueMRD™ Monitoring Test for MIBC.
