A study led by University College London suggests that millions of people with breast cancer might be able to avoid chemotherapy – after “practice-changing” trial results of a DNA test that could distinguish between which patients are likely to benefit from the treatment and those who are not.
The BBC reports that the international study found that more than two-thirds of its participants could be spared the side effects of chemotherapy and treated with hormone therapy alone.
The research involved more than 4 000 newly diagnosed patients over 40 in the UK, Norway, Sweden, Australia, New Zealand and Thailand.
Scientists used a gene test called Prosigna to measure the activity of 50 genes involved in breast cancer growth and calculate a patient’s risk of the disease returning.
Those who received a low score – two-thirds of the group – were not treated through chemotherapy. The five-year survival rate of their group was 93.7%, compared with a 94.9% rate among patients who received chemotherapy as part of their care.
The primary treatment for breast cancer is usually surgery to remove tumours. Chemotherapy is often recommended afterwards to diminish the risk of return. It is also regularly offered to people with early-stage breast cancer that has spread to the nearby lymph nodes.
Clinicians are concerned that the treatment provides little benefit to those with the most common type of breast cancer, UCL said.
The university said more than 5 000 NHS patients a year could avoid chemotherapy as a result of the trial.
The findings were presented this week at the world’s largest cancer conference, the American Society of Clinical Oncology’s annual meeting (ASCO, 29 May-2 June).
Professor David Miles, a leading cancer specialist, described the results as “practice-changing”.
“We can now confidently predict many patients will get no benefit at all, and therefore there’s no need for them to have the chemotherapy,” he said.
“We used to give chemotherapy to 100 women to benefit 10, knowing that 90 didn’t need it,” he added.
It is not known whether the findings apply to people under 40, with a result still several years away, according to UCL.
Study details
First results from the OPTIMA phase III randomised non-inferiority trial of test-directed chemotherapy in patients with high clinical risk ER-positive HER2-negative early breast cancer.
Robert Stein, Andreas Makris, Iain Macpherson et al.
Presented at 2026 ASCO meeting
Background
Tumour gene expression tests are widely used to assist adjuvant chemotherapy decisions for women with early breast cancer (EBC). OPTIMA (Optimal Personalised Treatment of early breast cancer using Multi-parameter Analysis) is an international RCT comparing chemotherapy decisions made with the Prosigna (PAM50) gene expression test with standard treatment in mostly node-positive patients.
Methods
Women and men aged >40 recommended to receive chemotherapy for ER+ HER2- EBC with 0-9 involved axillary nodes and T size >30mm if node negative were eligible. Randomisation was between standard chemotherapy followed by endocrine therapy (CET) or to a Prosigna test directed chemotherapy decision. Patients with Prosigna ROR score > 60 tumours were assigned CET whilst those with low ROR score (≤60) tumours received endocrine therapy (ET) alone. ET for premenopausal women included ovarian function suppression (OFS) in the absence of chemotherapy-induced ovarian insufficiency. ROR scores were not disclosed, and patients receiving CET were blinded to their randomisation. OPTIMA was designed to demonstrate non-inferiority (NI) of 5-year invasive breast cancer free survival (IBCFS) in the test-directed arm with a 3% margin in the per protocol (PP) population using a 5% 1-sided alpha. Control arm testing allowed treatment comparison within the low ROR score population at a 3.5% NI margin.
Results
From 16 Jan 2017 to 12 Dec 2025 4429 patients were randomised, 2215 to the control arm and 2214 to the test-directed arm of whom 2061 (93%) and 2097 (95%) were included in the respective PP group. Patient characteristics in the PP population were well-balanced; 62% were postmenopausal, 37% premenopausal and 0.8% male. 73% had pN1/pN1sn, 8% had pN0/pN1mi and 19% had pN2 tumours. 68% had low ROR score tumours.
With a median follow-up of 3.9 years (interquartile range 2.0-5.9), 280 IBCFS events occurred (141 on control arm; 139 on test directed arm) of which 66% were distant recurrences. The 5-year IBCFS rate in the control arm was 91.5% [95% CI 89.7- 92.9%] and 90.4% [95% CI 88.6- 92.0%] in the test-directed arm, Hazard Ratio (HR) 0.99 [90% CI 0.81- 1.20], NI p = 0.013, thereby meeting the pre-defined NI margin. The corresponding 5-year IBCFS rates for the low ROR score population were 94.9% [95% CI 92.9- 96.4%] and 93.7% [95% CI 91.8- 95.2%] for the two arms respectively, HR 1.06 [90% CI 0.78- 1.46] NI p = 0.0051 again demonstrating non-inferiority. There was no significant outcome heterogeneity between subgroups including for menopausal and nodal status.
Conclusions
The OPTIMA trial demonstrates that women and men with ER+ HER2- EBC and ROR score ≤60 tumours can safely avoid chemotherapy. It provides evidence for the utility of test-directed chemotherapy in premenopausal women treated with OFS and patients with high levels of nodal involvement.
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