New Genomic Test Helps High-Risk Breast Cancer Patients Safely Skip Chemotherapy

May 28, 2026 

A commercially available genomic test can now identify patients with early-stage, high-risk breast cancer who can safely skip chemotherapy. This marks a significant advancement in personalized cancer treatment that could spare thousands of individuals from the toxic side effects of unnecessary treatment while maintaining strong cancer-free survival rates.

The breakthrough comes from the OPTIMA phase III randomized non-inferiority trial, whose first results will be presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago this weekend. The study addresses one of oncology’s most pressing clinical questions: which breast cancer patients truly benefit from chemotherapy, and which can safely avoid it.

Key Findings from the OPTIMA Trial

The OPTIMA trial is a large-scale, prospective study using Veracyte’s Prosigna Breast Risk of Recurrence test to guide chemotherapy decisions. It specifically looks at patients with a high clinical risk who have hormone receptor-positive (ER-positive), HER2-negative early breast cancer.

The test combines the tumor’s intrinsic molecular subtypes and proliferation scores (how fast cells are dividing) with traditional clinical pathological factors into a single 10-year Risk of Recurrence (ROR) score.

The trial enrolled more than 4,400 patients to assess whether test-directed treatment is non-inferior to standard care (where everyone with high clinical risk receives chemotherapy).

“The OPTIMA trial results represent a major milestone in precision breast oncology and will provide Level 1A evidence supporting Prosigna-guided treatment decisions,” said Dr. Kelly Marcom, M.D., Veracyte’s Medical Director for Breast Cancer, who was not involved in the study execution. “These findings have the potential to transform how clinicians treat a large population of patients with breast cancer, helping them to personalize choices using genomic insights.”

Understanding the Prosigna Test

The Prosigna Breast Risk of Recurrence test is indicated for individuals who have undergone either a mastectomy or breast-conserving surgery. It provides prognostic information regarding distant recurrence-free survival at 10 years in two key populations:

• Node-Negative: Post-menopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer treated with adjuvant endocrine (hormone) therapy alone.

• Node-Positive: Post-menopausal women with HR+, lymph node-positive (1–3 positive nodes), Stage II or IIIA breast cancer treated with adjuvant endocrine therapy alone.

The assay calculates a score between 0 and 100, categorizing patients into low, intermediate, or high risk groups. In the context of the OPTIMA trial, the risk thresholds align with the biological behavior of the tumor:

Prosigna Risk Classification Scoring

Clinical Cutoff: In the OPTIMA protocol, patients with a Prosigna ROR score of 60 or less are classified as low risk and treated with endocrine therapy alone, while those with a score greater than 60 receive standard chemotherapy followed by hormone therapy.

The Clinical Challenge: When to Use Chemotherapy

When breast cancer is caught early and treated appropriately, the 5-year survival rate is high, sitting at approximately 91%. However, HR-positive breast cancer has a persistent risk of returning up to 20 years later. If a distant metastatic recurrence occurs (meaning the cancer spreads to other organs), survival drops significantly.

Historically, oncologists relied purely on clinical features like tumor size and age to recommend chemotherapy. However, traditional clinical factors often lead to overtreatment because they cannot accurately distinguish who will actually benefit from chemotherapy versus who can be safely managed with hormone pills alone.

“Together, these studies provide practice-changing evidence supporting the use of genomic tests in guiding treatment decisions,” noted Dr. Phillip Febbo, M.D., Veracyte’s Chief Scientific and Medical Officer. “In practice, this means clinicians can more confidently match treatment intensity to individual patient risk, helping ensure the right level of care while avoiding unnecessary treatment and its side effects.”

Practice-Changing Implications for Patients

For patients facing a new diagnosis, the validation of this test via the OPTIMA trial offers major quality-of-life and clinical benefits:

• Reduced Chemotherapy Exposure: Many individuals who would automatically receive chemotherapy based on tumor size or lymph node status can safely bypass it.

• Avoidance of Long-Term Toxicities: Chemotherapy can cause permanent damage, including cardiotoxicity (heart damage), neuropathy (nerve pain or numbness), cognitive decline (“chemo brain”), and rare secondary cancers like leukemia.

• True Precision Medicine: Treatment is dictated by the actual genetic makeup of the tumor rather than a one-size-fits-all protocol.

The Prosigna test is currently approved by the National Institute for Health and Care Excellence (NICE) in the UK for risk stratification and is fully covered on the NHS. For private pay environments, the test costs approximately £1,400.

Study Limitations and Considerations

While the data marks a significant milestone, oncology experts emphasize several important limitations that patients and physicians must consider:

• Tumor Subtype Restrictions: The Prosigna test is strictly validated for hormone receptor-positive (HR+), HER2-negative early breast cancer. It provides no clinical utility for triple-negative or HER2-positive breast cancer, which are biologically distinct and typically require standard chemotherapy.

• Menopausal Status: The current regulatory indications primarily target post-menopausal individuals. While trials are expanding data for pre-menopausal women, clinicians still exercise higher caution in younger patients due to different underlying estrogen environments.

• Nodal Involvement Cutoffs: The test is validated for patients with 0 to 3 positive lymph nodes. Patients with extensive nodal involvement (4 or more positive nodes) were not the focus of this de-escalation protocol and generally still require chemotherapy.

• The 20-Year Horizon: While the test provides an accurate 10-year outlook, HR+ breast cancer is notorious for very late recurrences, meaning regular clinical follow-up remains necessary regardless of the initial score.

Context: Genomic Testing Evolution

The OPTIMA trial builds upon a solid decade of genomic advancements in oncology. Prior landmarks, such as the TAILORx trial (which evaluated the Oncotype DX test) and studies on the MammaPrint assay, confirmed that low-genomic-risk patients with node-negative disease could skip chemotherapy.

What makes the OPTIMA data particularly practice-changing is its strong focus on a “higher-risk” population—including patients who have lymph node-positive disease—widening the safety net for chemotherapy de-escalation.

The full dataset from the OPTIMA trial will be formally presented by Principal Investigator Professor Robert Stein, Ph.D., of University College London, during the Breast Cancer Oral Abstract Session on Saturday, May 30, 2026, at 1:15 PM CT in Chicago. Veracyte is scheduled to host a formal investor and medical briefing on June 1, 2026, to discuss the immediate commercial and clinical integration of these results.

Medical Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.

References

• https://www.reuters.com/business/healthcare-pharmaceuticals/veracyte-genomic-test-identifies-breast-cancer-patients-who-can-skip-chemo-2026-05-27/