Genomic Test Lets High-Risk Breast Cancer Patients Skip Chemo

A genomic test can now flag which women with higher-risk breast cancer can safely skip chemotherapy, according to results from the OPTIMA trial presented on Saturday at the world’s largest cancer meeting. In the study, 68% of patients whose tumours had spread to the lymph nodes avoided chemo, and their survival five years later barely differed from women who went through it.

That spares patients the nausea, hair loss and lasting harms of chemotherapy. It also pushes genomic risk scoring into a group oncologists have treated with chemotherapy almost by reflex for three decades: women whose cancer has reached the lymph nodes.

Two-Thirds of High-Risk Patients Skipped Chemotherapy Safely

The OPTIMA trial (Optimal Personalised Treatment of early breast cancer using Multi-parameter Analysis) followed 4,429 patients aged 40 and over across the UK, Norway, Sweden, Australia, New Zealand and Thailand. Every participant had hormone-receptor-positive, HER2-negative disease (HR+/HER2-, the most common breast cancer subtype, accounting for up to 80% of cases) that had already spread to the lymph nodes.

Half were randomly assigned the standard path: chemotherapy followed by hormone therapy. The other half had their tumours scored by the genomic test. A low score meant hormone therapy alone. A high score kept chemotherapy in the plan, and radiotherapy and other care continued as normal for both groups.

Two-thirds of the tested patients scored low and went without chemo. The UCL-led OPTIMA breast cancer trial, run by University College London (UCL) and funded partly by the National Institute for Health and Care Research (NIHR, the UK’s public health research body), reported outcomes that landed within roughly a single percentage point.

• 68% of node-positive patients who were tested avoided chemotherapy
• 93.7% of low-score patients on hormone therapy alone were alive and free of invasive breast cancer at five years
• 94.9% of patients in the standard chemotherapy group reached the same five-year mark
• 4.0 years was the median follow-up across all 4,429 participants

Why Node-Positive Results Break New Ground

Genomic de-escalation is not new. The 2018 TAILORx trial and the later RxPONDER study showed that many women with little or no lymph-node involvement could drop chemotherapy on the strength of a gene score, and guidelines shifted to match. Detection has steadily improved through tools like routine mammogram screening for early detection, and treatment is now following with the same drive toward tailoring.

Spread to the lymph nodes was the line doctors were reluctant to cross. Node involvement has long been read as a warning that stray cancer cells may already be circulating, and chemotherapy was the insurance policy. OPTIMA is the first large randomised trial to test whether a gene score can override that instinct in node-positive disease, and it ran the question across six countries to get there.

An earlier feasibility phase, reported in an earlier OPTIMA feasibility study, had suggested the approach could work before the full trial confirmed it.

Optima provides robust, practice-changing evidence that we can safely reduce the use of chemotherapy for many patients with hormone-sensitive breast cancer.

That assessment came from Iain MacPherson, a co-chief investigator on the trial and professor of breast oncology at the University of Glasgow. Rob Stein, the chief investigator and a professor of breast oncology at UCL, framed the result as using tumour biology, rather than clinical features alone, to decide who truly needs chemotherapy.

How the 50-Gene Prosigna Score Works

The genomic test at the centre of the trial is the Prosigna test, made by the diagnostics company Veracyte. It reads the activity of 50 genes (the PAM50 signature) in a sample of tumour tissue and returns two things: the cancer’s molecular subtype and a Risk of Recurrence (ROR) score, a number that estimates the chance of the disease coming back over the next ten years.

In the trial, the cutoff was set at 60. Patients scoring 60 or below were treated as low risk and offered hormone therapy alone; those above 60 stayed on chemotherapy. The company is due to walk through the full data set in Chicago, with Veracyte’s Prosigna presentation schedule at ASCO listing the breast cancer oral session.

• Classifies the tumour into a molecular subtype, such as luminal A or luminal B
• Generates an ROR score from 0 to 100 tied to ten-year recurrence risk
• Works from a standard tumour tissue sample already taken during surgery
• Gives oncologists a biology-based figure to weigh against tumour size and node count

The De-escalation Push Reaches a Costlier Group

Sparing two-thirds of node-positive patients from chemotherapy is not only a clinical shift. It changes the arithmetic for health systems that pay for the drugs, the infusion-chair hours and the long tail of managing side-effects.

A Crowded Field of Genomic Tests

The Prosigna test is not the only player. Two rival tests have shaped chemotherapy decisions for years, and each is tied to its own landmark trial.

What sets the new result apart is the population. TAILORx focused on node-negative disease and RxPONDER on patients with one to three positive nodes, while OPTIMA went after a broader, higher-risk node-positive group, the slice where doctors had the least genomic evidence to lean on.

What Skipping Chemo Means for Budgets

The patient pool is large. In the United States alone, more than 225,000 people are diagnosed with HR+/HER2- breast cancer each year, and a sizeable share have node-positive disease. The wider trend mirrors a push across oncology toward precision diagnostics, the same logic behind a blood test added to colorectal cancer screening and other tools now entering guidelines.

For the UK’s NHS, part of the case is financial: skipping chemotherapy avoids drug costs and weeks of clinic visits, and the test fee is small against an averted course of treatment. Stein called it a more efficient, evidence-based use of resources, the kind of line that tends to speed adoption. The detailed numbers sit in the full OPTIMA results released by Veracyte.

What the Five-Year Data Does Not Yet Settle

The result is strong, but it is not the final word. Hormone-driven breast cancers are slow, and they can return well beyond the five-year window where the survival curves currently sit. With a median follow-up of four years, the longer-term picture is still forming.

Some subgroups carried wide margins of uncertainty. Among premenopausal women receiving ovarian suppression, and among patients with extensive nodal spread of four to nine nodes, the confidence intervals were broad enough that doctors are likely to stay cautious before withholding chemotherapy. Too few men took part for any firm conclusion in that group.

The headline numbers were presented as a conference abstract and still face full peer review and publication. That does not erase the core finding, but it sets the pace at which guidelines will move.

If the survival curves hold past ten years, the test rewrites the standard of care for node-positive breast cancer; if late recurrences creep into the no-chemo group, the guidance will be pulled back quickly. For now, most higher-risk patients in the trial have a credible reason to ask their oncologist whether chemotherapy is something they can leave behind.

Frequently Asked Questions

What is the OPTIMA breast cancer trial?

OPTIMA is a phase III randomised trial led by University College London that enrolled 4,429 patients across six countries to test whether a genomic score can safely guide chemotherapy decisions in node-positive, hormone-receptor-positive breast cancer. Results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on 30 May.

Which breast cancer patients might be able to skip chemotherapy?

In the trial, patients with HR+/HER2- breast cancer that had spread to the lymph nodes and who scored 60 or below on the Prosigna Risk of Recurrence scale were treated with hormone therapy alone. That covered 68% of the tested group.

How does the Prosigna test decide who needs chemo?

The Prosigna test reads the activity of 50 genes in tumour tissue and produces a Risk of Recurrence score from 0 to 100, alongside the cancer’s molecular subtype. A higher score signals a greater ten-year recurrence risk and supports adding chemotherapy.

Was skipping chemotherapy safe in the results?

Over five years, 93.7% of low-score patients who took hormone therapy alone were alive and free of invasive breast cancer, compared with 94.9% of those who all received chemotherapy. The roughly one-point gap was not considered clinically meaningful, though follow-up continues.

Will these findings change treatment guidelines?

Not immediately. The data was presented as a conference abstract and still needs full peer review and publication, and longer follow-up is needed because hormone-driven cancers can recur after five years. If the results hold, guideline committees are expected to weigh them for node-positive patients.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Breast cancer treatment decisions, including whether to use or avoid chemotherapy, should be made with a qualified oncologist who knows your individual case. Trial figures cited are accurate as of publication and reflect results presented at a scientific conference that have not yet completed full peer review.