Gene test can safely spare breast cancer patients of chemotherapy

The OPTIMA trial suggests that people aged 40 and above 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.

People with breast cancer will be able to safely avoid chemotherapy with the use of a gene test, potentially sparing them unnecessary side effects without increasing the risk of the cancer returning, according to clinical trials led by University College London (UCL). 

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 suggest that people aged 40 and above 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.

What does the study say?

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. The test is performed on cancer tissue samples.

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 a significant step toward more personalised treatment. For patients, this means many may be spared the physical and emotional burden of chemotherapy and its potential long-term side effects.”

The OPTIMA trial recruited women and men aged 40 or older following surgery for hormone-sensitive breast cancer. Most had their cancer spread to underarm 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.

Key findings of the study

Of the 4,429 people who took part in the trial, more than two-thirds (68 per cent) 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 per cent of those who received chemotherapy alongside hormone therapy were alive and free from breast cancer recurrence

• 93.6 per cent of those treated with hormone therapy alone were also alive and recurrence-free

A statistical test showed that at most, only 2 per cent 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.

Researchers estimate that more than 5000 NHS patients a year could avoid chemotherapy because of this trial.

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.

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 results for the same may take several years.

A positive outcome

Karen Bonham, 64, from Cardiff, was diagnosed with breast cancer after attending routine screening in June 2017. She underwent a left mastectomy and axillary node clearance two months later. Results showed a large but slowly growing hormone-sensitive cancer with two affected lymph nodes. Chemotherapy is the standard treatment for this type of breast cancer.

Karen learnt about the OPTIMA trial and was interested in participating in it. 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.

Instead of chemotherapy, Karen went on to receive radiotherapy and hormone therapy, completing eight years of active treatment. She feels the trial allowed her to receive a more targeted treatment and brought positive outcomes.