For decades, one of the most difficult decisions in breast cancer treatment has been knowing who genuinely needs chemotherapy.

Chemotherapy can significantly reduce the risk of cancer returning, but the price is substantial: months of treatment, fatigue, nausea, hair loss and the possibility of serious longer-term side effects. The problem is that for some patients, those burdens may bring very little additional benefit.

A major international trial led from the UK has now provided some of the strongest evidence yet that tumour biology can be used to identify many of those patients before chemotherapy begins.

The findings could allow more than 5,000 NHS breast cancer patients every year to safely avoid chemotherapy altogether.

The Question OPTIMA Set Out to Answer

The OPTIMA trial followed 4,429 women and men aged 40 and over with hormone-sensitive early breast cancer.

Many were considered at relatively high risk of recurrence based on traditional clinical measures. Most had cancer that had spread to nearby lymph nodes and, under conventional treatment pathways, would normally have been offered chemotherapy alongside hormone therapy.

OPTIMA asked a deceptively simple question: could analysing the biology of the tumour itself reveal which of those patients actually stood to benefit from chemotherapy?

Researchers used Prosigna, a genomic test that measures the activity of genes associated with breast cancer growth in tumour tissue.

The test produces a Risk of Recurrence, or ROR, score. Patients in the test-directed arm whose tumours scored above 60 received chemotherapy followed by hormone therapy. Those with a score of 60 or below received hormone therapy without chemotherapy.

More than two-thirds of patients tested – 68% – fell into that lower-scoring group.

What Happened When Chemotherapy Was Removed?

Five years later, the difference was remarkably small.

Among patients with a low Prosigna score, 94.8% of those who received chemotherapy alongside hormone therapy were alive without their breast cancer returning.

Among those treated without chemotherapy, the figure was 93.6%.

The trial was specifically designed to determine whether test-directed treatment was clinically non-inferior to conventional treatment, and the results met that threshold. Researchers calculated that, at most, only around 2% of patients with a low Prosigna score were likely to benefit from chemotherapy.

That distinction matters.

Chemotherapy remains an essential and potentially life-saving treatment for many people with breast cancer. OPTIMA does not challenge that.

Instead, it suggests that the way clinicians decide who receives it could become considerably more precise.

From Clinical Risk to Tumour Biology

Genomic testing in breast cancer is not new. Tests that analyse the biological characteristics of tumours are already used to help guide treatment for some patients.

What makes OPTIMA significant is the population it studied.

Previous research has often focused on patients with more limited disease or lower clinical risk. OPTIMA included patients whose traditional clinical characteristics could have pushed doctors towards recommending chemotherapy, including women with more extensive lymph-node involvement.

The results therefore challenge a long-established assumption: that a patient who appears high-risk according to factors such as tumour size and lymph-node involvement must automatically benefit from chemotherapy.

Tumours that look similar clinically can behave very differently at a molecular level.

Genomic testing provides another layer of information, allowing treatment decisions to be based not only on where a cancer is and how large it has become, but on what is happening inside its cells.

That is personalised medicine in its most practical form: not developing a completely new treatment, but using biological information to determine when an existing one is actually necessary.

Fewer Side Effects, More Targeted Treatment

For patients, the benefit is immediate.

Avoiding chemotherapy means avoiding weeks or months of treatment and many of the associated effects, including fatigue, nausea, hair loss and increased susceptibility to infection, as well as some less common but potentially serious long-term complications.

There is also a wider healthcare impact.

Chemotherapy requires specialist staff, treatment facilities, monitoring and repeated hospital visits. Identifying thousands of patients who can safely avoid it could reduce pressure on NHS oncology services while allowing resources to be concentrated on those who genuinely need treatment.

Researchers estimate that the OPTIMA findings could ultimately allow more than 5,000 NHS patients each year to avoid unnecessary chemotherapy.

There is another practical advantage. Prosigna does not require an entirely new diagnostic infrastructure. The test uses tumour tissue already collected during surgery or biopsy and can be carried out by NHS laboratories with the appropriate equipment.

The Questions That Remain

The findings do not apply to every breast cancer patient.

OPTIMA studied people aged 40 and over with hormone-sensitive early breast cancer, meaning the results cannot simply be extended to other breast cancer subtypes or younger patients.

Importantly, the study did include both premenopausal and postmenopausal women, and researchers found similar outcomes between the groups. However, it is not yet known whether the same approach can safely be applied to patients under 40. Further OPTIMA research is expected to provide additional evidence around treatment decisions for younger and premenopausal patients.

The results will also feed into decisions by bodies including the National Institute for Health and Care Excellence over wider NHS access to Prosigna testing and its cost-effectiveness.

A Different Kind of Breakthrough

Some of the most important advances in life sciences arrive as entirely new medicines, devices or technologies.

Others come from learning when not to treat.

OPTIMA falls firmly into the second category.

The trial does not replace chemotherapy. It provides clinicians with better information about who is likely to benefit from it, potentially allowing thousands of people to receive less intensive treatment without sacrificing their chances of remaining cancer-free.

It is also a strong example of the role the UK continues to play in large-scale clinical research. UCL sponsored the study, the University of Warwick coordinated trial delivery and analysis, and researchers from Glasgow, Edinburgh, Leeds and Bristol contributed alongside hospitals and international partners across six countries. In total, 115 UK hospitals recruited patients into the trial.

As life sciences moves increasingly towards precision medicine, the significance of studies like OPTIMA goes beyond breast cancer.

The principle is simple: the better we understand the biology of an individual patient’s disease, the less we have to rely on treating everyone in the same way.

For thousands of breast cancer patients, that could mean receiving exactly as much treatment as they need – and no more.

Sources include University College London, the OPTIMA trial, the American Society of Clinical Oncology and the NIHR.