Many people with breast cancer can safely avoid chemotherapy with the use of a gene test, potentially sparing them unnecessary side effects without increasing the risk of the cancer returning, a large international clinical trial led by UCL has found.
The OPTIMA trial (Optimal Personalised Treatment of early breast cancer using Multi-parameter Analysis) was designed to reduce the use of unnecessary chemotherapy for people with newly diagnosed breast cancer. It followed more than 4,400 patients across the UK, Norway, Sweden, Australia, New Zealand and Thailand.
The findings, to be presented at 2026 American Society of Clinical Oncology (ASCO) meeting in Chicago this month, suggest that people aged 40 and over whose tumours have a low Prosigna test score can be treated safely with hormone therapy alone, potentially transforming care for thousands of patients each year.
Chemotherapy is regularly offered to people with early‑stage breast cancer that has spread from the breast to nearby lymph nodes, as it lowers the risk of the disease returning. While effective overall, there is concern among clinicians that many people with the most common, hormone‑sensitive type of breast cancer receive little or no benefit from chemotherapy but still experience its significant and sometimes dangerous side effects.
OPTIMA set out to address this dilemma by using a genomic test from Veracyte called Prosigna, which measures the activity of genes involved in breast cancer growth. Unlike some similar tests, Prosigna can be run by NHS laboratories with the appropriate equipment.
The test is performed on cancer tissue samples. Typically, these are tumours removed at surgery but as the test uses very little tissue, it also works on diagnostic needle biopsies.
Chief Investigator of the OPTIMA trial and Professor of Breast Oncology at the UCL Cancer Institute, Professor Rob Stein said: "OPTIMA addresses a long-standing challenge in breast cancer care: identifying who truly benefits from chemotherapy and who does not. Our findings show that many patients can safely avoid chemotherapy without compromising their outcomes.
"These results mark an important and significant step toward more personalised treatment. The trial has successfully used tumour biology to guide decisions rather than relying solely on traditional clinical features. For patients, this means many may be spared the physical and emotional burden of chemotherapy and its potential long-term side effects. For health systems, it represents a more efficient and evidence-based use of resources."
The OPTIMA trial recruited women and men aged 40 or older following surgery for hormone-sensitive breast cancer. Most had their cancer spread to under arm lymph nodes which placed them at high risk of future recurrence. Because of this, their usual treatment included both a course of chemotherapy and standard hormone tablets taken for five to ten years.
Participants were randomly assigned to one of two groups:
- Standard treatment group: patients received chemotherapy followed by hormone therapy.
- Test‑directed group: patients had their tumour tested using Prosigna. Those with a high score (above 60) received chemotherapy and hormone therapy, while those with a low score (less than or equal to 60) were treated with hormone therapy alone.
Radiotherapy and other treatments were given as usual in both groups.
The trial was designed to assess whether test‑directed treatment would or would not lead to a meaningful increase in the number of people whose cancer returned or who died within five years. In consultation with patients and clinicians, the researchers defined an acceptable difference as no more than 3%.
Key findings
Of the 4,429 people who took part in the trial, more than two-thirds (68%) had a low Prosigna score.
For this group, the results showed that outcomes were very similar whether chemotherapy was given or not. Five years after treatment:
- 94.8% of those who received chemotherapy alongside hormone therapy were alive and free from breast cancer recurrence
- 93.6% of those treated with hormone therapy alone were also alive and recurrence-free
A statistical test showed that at the most, only 2% of patients with a low Prosigna score treated with chemotherapy will benefit from this treatment.
This suggests that for patients with low Prosigna scores, chemotherapy offers little or no additional benefit, meaning many people could safely avoid it and its side effects.
Overall, the findings indicate that using the Prosigna test to guide treatment decisions could help a substantial number of patients avoid unnecessary chemotherapy without compromising their outcomes. Researchers estimate more than 5000 NHS patients a year could avoid chemotherapy because of this trial.
Results for the full trial population will be used to inform decision-making by healthcare bodies such as the National Institute for Health and Care Excellence (NICE), about wider NHS access to Prosigna testing, by demonstrating that test‑directed treatment is cost‑effective. The results also show similarly high survival rates, but reflect a broader mix of patients, including those at higher risk of recurrence.
The research team also examined whether the findings differed for specific groups of patients. Outcomes were similar for pre‑ and post‑menopausal women, and no differences were seen based on the number of affected lymph nodes, including in people whose cancer had spread to more than three nodes.
Some men did take part in the study but there were too few to draw firm conclusions for this group.
Impact
The results show that people aged 40 or older with hormone‑sensitive breast cancer and a low Prosigna score can safely avoid chemotherapy.
Unlike previous studies, which mainly focused on postmenopausal women with limited lymph node involvement, OPTIMA included premenopausal women and patients with more extensive disease. Premenopausal women in the trial received hormone therapy that temporarily suppresses ovarian function, which the researchers believe explains why chemotherapy did not appear to offer additional benefit in this group.
The team cautions that it is not yet known whether the findings apply to people under the age of 40. The next phase of OPTIMA aims to generate further information about test use for premenopausal women but a result is still several years away.
Co-chief Investigator and Professor of Breast Oncology at the University of Glasgow, Professor Iain MacPherson, said: "OPTIMA provides robust, practice‑changing evidence that we can safely reduce the use of chemotherapy for many patients with hormone‑sensitive breast cancer.
"These findings represent a major step forward in delivering more personalised, precise care, ensuring that treatment decisions are driven by what will genuinely improve outcomes for patients, while avoiding unnecessary toxicity. The potential impact for both patients and health services is substantial."
Patient's story
Karen Bonham, 64, from Cardiff, was diagnosed with breast cancer after attending routine screening in June 2017. Married with two children, Karen had worked as a speech and language therapist for 40 years
She was recalled to the breast clinic at Velindre Cancer Centre in Cardiff within two weeks of screening, where a biopsy confirmed left-sided breast cancer. Karen underwent a left mastectomy and axillary node clearance in July 2017. Results showed a large (>5cm) but slowly growing hormone sensitive cancer with two affected lymph nodes. Chemotherapy is the standard treatment for this type of breast cancer.
Karen said: "Cancer diagnosis and treatment can be shocking. It certainly propels you into a world of uncertainty. Life priorities realign- you simply want to survive.
"Life certainly becomes busy – a whirlwind of appointments, information and rapid decision-making. All while trying to keep a sense of normalcy for your family, especially when children may be confronting GCSE's, Uni finals."
Karen became aware of the OPTIMA trial during one of her first oncology appointments in September 2017 while discussing the possibility of chemotherapy, a treatment she was dreading. Karen told her doctors she was interested in being a part of new research that could support patient outcomes, and dared to hope she would not need chemotherapy.
The Prosigna test was carried out on tissue stored from Karen's breast surgery while plans were already being made for standard chemotherapy to begin. Karen said she was only days away from starting treatment and had "already cut my hair short" when the results came back just over two weeks later.
While walking on a local beach, Karen received a phone call from her hospital telling her she'd been allocated to the test-directed group of the trial and did not require chemotherapy.
She said: "How to describe the initial feeling? Immense relief? Like Christmas? Certainly a mixture of the two."
Instead of chemotherapy, Karen went on to receive radiotherapy and hormone therapy, completing eight years of active treatment.
Now almost nine years on from her diagnosis, Karen says she does not feel defined by cancer and has returned to normal family life. She remains active, enjoying walking and yoga, and says taking part in the OPTIMA trial "helped decision making to allow me to receive targeted, appropriate treatment more quickly and has enabled my positive health outcome."
