Landmark OPTIMA Trial Demonstrates Veracyte’s Prosigna Test Can Safely Reduce Chemotherapy Use in High-Risk Breast Cancer Patients
Veracyte has announced groundbreaking results from the OPTIMA (Optimal Personalised Treatment of Early Breast Cancer Using Multi-parameter Analysis) trial, a large independent Phase III study that could significantly reshape treatment decisions for patients with early-stage hormone receptor-positive, HER2-negative breast cancer. The findings, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, provide the strongest prospective evidence to date that the Prosigna Breast Risk of Recurrence (ROR) test can accurately identify patients who may safely avoid chemotherapy without compromising clinical outcomes.
The study represents a major advancement in precision oncology by demonstrating that treatment decisions can be guided more effectively by tumor biology rather than traditional clinical risk factors alone. Researchers found that more than two-thirds of patients classified as clinically high risk could forgo chemotherapy and still achieve outcomes comparable to those who received standard chemotherapy treatment.
A New Approach to Breast Cancer Treatment Decisions
For decades, decisions regarding adjuvant chemotherapy in breast cancer have largely been based on clinical characteristics such as tumor size, patient age, and the extent of lymph node involvement. While these factors provide valuable information, they do not always accurately predict whether an individual patient will benefit from chemotherapy.
As a result, many patients undergo aggressive treatment despite receiving limited benefit, exposing them to potentially severe short- and long-term side effects. These may include fatigue, nausea, immune suppression, cardiovascular complications, cognitive impairment, and persistent nerve damage that can affect quality of life for years after treatment.
The OPTIMA trial sought to address this challenge by evaluating whether genomic information generated by the Prosigna test could more precisely guide treatment decisions and reduce unnecessary chemotherapy use.
“Behind every breast cancer treatment decision is a patient asking, ‘Do I really need chemotherapy?’” said Professor Robert Stein, lead investigator of the OPTIMA trial from University College London. According to Stein, the trial provides compelling evidence that clinicians can now answer that question with greater confidence for a large proportion of high-risk patients.
Trial Design and Patient Population
OPTIMA was designed as a prospective, randomized controlled Phase III trial, widely regarded as the gold standard for evaluating medical interventions. The study enrolled 4,429 patients with early-stage estrogen receptor-positive (ER-positive), HER2-negative breast cancer who were considered clinically high risk and had lymph node-positive disease.
Participants were assigned to one of two treatment strategies. Patients in the standard-of-care group received chemotherapy followed by hormone therapy, reflecting current clinical practice for many high-risk individuals.
Patients in the biomarker-guided treatment group underwent testing with the Prosigna assay. Those receiving a Risk of Recurrence score above 60 were treated with chemotherapy followed by hormone therapy, while patients with scores of 60 or below received hormone therapy alone.
Researchers then compared cancer outcomes between the groups to determine whether chemotherapy could safely be omitted in selected patients identified by the genomic test.
More Than Two-Thirds of Patients Avoided Chemotherapy
One of the most significant findings from the trial was the ability of the Prosigna test to identify patients who could safely avoid chemotherapy.
The study showed that 68 percent of patients who would traditionally have been recommended chemotherapy based on clinical risk factors alone were able to forgo the treatment entirely. Importantly, these patients maintained excellent outcomes.
Patients treated without chemotherapy achieved a five-year cancer-free survival rate of 93.7 percent, compared with 94.9 percent among patients who received chemotherapy. Statistical analysis demonstrated that outcomes were non-inferior, meaning that avoiding chemotherapy did not lead to a meaningful increase in recurrence risk or compromise disease control.
These findings suggest that a substantial proportion of patients currently receiving chemotherapy may be undergoing treatment that provides little additional benefit.
By identifying those patients in advance, clinicians may be able to reduce treatment burden while maintaining excellent clinical outcomes.
Strong Evidence Across Traditionally High-Risk Groups
Another notable aspect of the OPTIMA study was its inclusion of patient populations that have historically presented significant uncertainty regarding chemotherapy decisions.
Previous research evaluating genomic tests has often focused on lower-risk populations, leaving unanswered questions about whether similar approaches could be applied safely to patients with more aggressive disease characteristics.
OPTIMA specifically addressed this gap.
Researchers demonstrated that the Prosigna-guided strategy remained effective among premenopausal women receiving ovarian function suppression therapy. In this subgroup, outcomes were comparable between patients who avoided chemotherapy and those who received standard treatment.
The trial also included patients with extensive lymph node involvement, including those with four to nine positive lymph nodes, a population often considered at particularly high risk for recurrence. Results confirmed that treatment decisions based on tumor biology remained appropriate even in these patients.
These findings reinforce the concept that genomic characteristics can provide more meaningful information about recurrence risk and treatment benefit than clinical features alone.
Achieving the Highest Level of Clinical Evidence
The OPTIMA trial delivers what researchers describe as Level 1A evidence, the highest standard of clinical validation available for treatment-guiding biomarkers.
With more than 4,400 participants and a median follow-up period of four years, the study provides robust prospective data supporting the clinical utility of the Prosigna test.
Such evidence is particularly important because treatment recommendations in oncology increasingly rely on biomarker-driven approaches. Clinicians and guideline committees typically require large prospective trials before adopting new standards of care.
The OPTIMA findings therefore position the Prosigna assay among the most extensively validated genomic tests available for breast cancer treatment decision-making.
Understanding the Prosigna Test
The Prosigna Breast Risk of Recurrence test evaluates the biological characteristics of a patient’s tumor to estimate the likelihood of cancer recurrence.
Unlike traditional approaches that focus primarily on clinical and pathological features, the test analyzes gene expression patterns associated with tumor behavior. It combines intrinsic breast cancer subtype information, tumor proliferation measures, and clinical-pathological data to generate an individualized Risk of Recurrence score.
This score helps physicians determine whether a patient is likely to benefit from chemotherapy.
In the OPTIMA trial, a score below 60 identified patients who could safely avoid chemotherapy while maintaining excellent long-term outcomes. Patients with scores above 60 continued to receive chemotherapy, ensuring that individuals most likely to benefit from treatment were appropriately managed.
This personalized approach supports the broader movement toward precision medicine, where treatment strategies are tailored to the unique biology of each patient’s disease.
Implications for Patients
Breast cancer remains the most frequently diagnosed cancer among women worldwide. In the United States alone, more than 225,000 new cases of hormone receptor-positive, HER2-negative breast cancer are diagnosed annually.
Because chemotherapy can have substantial physical, emotional, and financial consequences, the ability to avoid unnecessary treatment represents a significant advancement for patients.
Research has shown that many breast cancer survivors continue to experience treatment-related side effects years after completing chemotherapy. Persistent nerve damage, cognitive difficulties, fatigue, and reduced quality of life are among the challenges frequently reported.
By reducing chemotherapy exposure without sacrificing effectiveness, the Prosigna-guided strategy has the potential to improve survivorship experiences for thousands of patients each year.
For many women, avoiding chemotherapy may also reduce disruptions to family responsibilities, employment, and daily activities during treatment.
Potential to Influence Clinical Practice
According to Veracyte Chief Scientific and Medical Officer Dr. Phillip Febbo, the OPTIMA results establish a new benchmark for chemotherapy decision-making in breast cancer.
He noted that the trial provides the strongest prospective evidence yet demonstrating that a genomic test can identify clinically high-risk patients who may safely avoid chemotherapy.
The findings are expected to attract significant attention from oncologists, professional societies, and guideline committees evaluating future treatment recommendations.
If incorporated into routine clinical practice, the results could lead to broader adoption of biomarker-guided treatment strategies and a shift away from relying solely on traditional clinical risk factors.
As healthcare systems increasingly emphasize personalized medicine, the OPTIMA trial offers compelling evidence that genomic testing can help optimize treatment decisions while reducing unnecessary interventions.
Presented during the Breast Cancer—Local/Regional/Adjuvant Oral Abstract Session at the 2026 ASCO Annual Meeting, the study marks a significant milestone in the evolution of breast cancer care and highlights the growing role of precision diagnostics in improving outcomes for patients worldwide.
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.
