Many breast cancer patients may be able to safely avoid chemotherapy using genetic testing, potentially avoiding unnecessary side effects without increasing the risk of cancer recurrence, a large UCL-led international clinical trial has found.
The OPTIMA trial (Optimal Personalized Treatment of Early Breast Cancer Using Multiparameter Analysis) was designed to reduce the use of unnecessary chemotherapy for people newly diagnosed with breast cancer. More than 4,400 patients were followed in the UK, Norway, Sweden, Australia, New Zealand and Thailand.
The findings, to be presented this month at the 2026 American Society of Clinical Oncology (ASCO) meeting in Chicago, suggest that people over age 40 with low tumor prosigna test scores can be safely treated with hormone therapy alone, potentially changing care for thousands of patients each year.
Chemotherapy is routinely given to patients with early-stage breast cancer that has spread from the breast to nearby lymph nodes to reduce the risk of the disease coming back. Although overall effective, there is concern among clinicians that many of the most common hormone-sensitive types of breast cancer receive little or no benefit from chemotherapy but experience serious and sometimes dangerous side effects.
OPTIMA set out to address this dilemma using Veracyte’s genomic test called Prosigna, which measures the activity of genes involved in breast cancer growth. Unlike other similar tests, Prosigna can be carried out in NHS laboratories with appropriate equipment.
This test is done on a sample of cancer tissue. These tumors are usually removed surgically, but because this test uses so little tissue, it can also be used for a diagnostic needle biopsy.
Professor Rob Stein, Principal Investigator of the OPTIMA trial and Professor of Breast Cancer at the UCL Institute of Cancer Research, said: “OPTIMA addresses a long-standing challenge in breast cancer treatment: identifying who truly benefits from chemotherapy and who does not. Our findings show that many patients can safely avoid chemotherapy without compromising outcomes.”
“These results represent an important and significant step towards more individualized treatments. This trial successfully used tumor biology to guide decision-making, rather than relying solely on traditional clinical features. For patients, this means many may be spared the physical and mental burden of chemotherapy and its potential long-term side effects. For health systems, this means a more efficient, evidence-based use of resources.”
The OPTIMA trial enrolled women and men aged 40 and older after surgery for hormone-sensitive breast cancer. Most had cancer that had spread to lymph nodes in their armpits and were at high risk of recurrence in the future. Because of this, their usual treatment included a course of chemotherapy and taking standard hormone pills for five to 10 years.
Participants were randomly assigned to one of two groups:
- Standard treatment group: The patient received chemotherapy followed by hormone therapy.
- test‑Indicated group: The patient was tested for the tumor using Prosigna. Those with high scores (above 60) received chemotherapy and hormone therapy, while those with low scores (below 60) were treated with hormone therapy alone.
Radiation therapy and other treatments were administered as usual in both groups.
The trial was designed to assess whether test-driven treatment leads to a significant increase in the number of cancer recurrences or deaths within five years. After consultation with patients and clinicians, the researchers defined an acceptable difference as 3% or less.
Main findings
Of the 4,429 people in the trial, more than two-thirds (68%) had low Prosigna scores.
Results showed that for this group, outcomes were very similar whether chemotherapy was given or not. 5 years after treatment:
- 94.8% of those who received chemotherapy along with hormone therapy survived and did not experience breast cancer recurrence.
- 93.6% of patients treated with hormone therapy alone also survived and had no recurrence.
Statistical tests showed that at most only 2% of patients with low Prosigna scores treated with chemotherapy benefit from this treatment.
This means that for patients with low Prosigna scores, there is little or no additional benefit from chemotherapy, and many can safely avoid chemotherapy and its side effects.
Overall, the results of this study demonstrate that by using Prosigna testing to guide treatment decisions, a significant number of patients may be able to avoid unnecessary chemotherapy without compromising outcomes. Researchers estimate that more than 5,000 NHS patients a year will be able to avoid chemotherapy thanks to this trial.
Results from all trial participants will be used to inform decision-making by healthcare organizations such as the National Institute for Healthcare Excellence (NICE) on expanding NHS access to Prosigna testing by demonstrating that test-driven treatment is cost-effective. The results show similarly high survival rates but reflect a broader patient mix, including those at high risk of recurrence.
The research team also looked at whether the results differed in specific patient groups. Outcomes were similar for premenopausal and postmenopausal women, including those whose cancer had spread to three or more lymph nodes, and there were no differences based on the number of lymph nodes affected.
Some men participated in the study, but there were too few to draw firm conclusions about this group.
impact
These results indicate that hormone-sensitive breast cancer patients over 40 years of age with low Prosigna scores can safely avoid chemotherapy.
Unlike previous studies, which primarily focused on postmenopausal women with limited lymph node metastases, OPTIMA included premenopausal women and patients with a broader range of disease. The premenopausal women in this trial were receiving hormone therapy to temporarily suppress ovarian function, which the researchers believe explains why chemotherapy had no additional benefit in this group.
The research team cautioned that it is still unclear whether the findings apply to people under 40. The next phase of OPTIMA aims to generate more information on the use of the test in premenopausal women, but results are still several years away.
OPTIMA provides strong practice-changing evidence that chemotherapy use can be safely reduced for many hormone-sensitive breast cancer patients.
These findings represent a major step forward in providing more personalized and precise care, ensuring treatment decisions are based on what truly improves patient outcomes while avoiding unnecessary toxicity. The potential impact on both patients and health services is significant. ”
Professor Ian McPherson, Co-Principal Investigator and Professor in Breast Oncology, University of Glasgow
patient’s story
Karen Bonham, 64, from Cardiff, was diagnosed with breast cancer after a routine check-up in June 2017. Karen, who is married with two children, has worked as a speech therapist for 40 years.
She was recalled to the Breast Clinic at Berindre Cancer Center in Cardiff within two weeks of her screening, where a biopsy confirmed a left-sided breast cancer. Karen underwent a left mastectomy and axillary lymph node removal in July 2017. The results showed that I had a large (>5cm), slow-growing, hormone-sensitive cancer that affected two lymph nodes. Chemotherapy is the standard treatment for this type of breast cancer.
Karen said: “Cancer diagnosis and treatment is shocking. It certainly puts you into a world of uncertainty. Life priorities are readjusted and you just hope to survive.”
“Life can definitely get hectic with a whirlwind of plans, information and quick decisions, and families need to try to maintain some sense of normalcy, especially when children may be facing GCSEs or university finals.”
Karen learned about the OPTIMA trial during her first medical oncology visit in September 2017, when she was discussing the possibility of chemotherapy, a treatment she had feared. Karen told her doctors that she was interested in participating in new research that would support patient outcomes and dared to hope that chemotherapy would no longer be necessary.
The Prosigna test was performed on tissue saved from Karen’s breast surgery while plans were already in place to begin standard chemotherapy. Karen said she was just days away from starting treatment and when she got her results back just two weeks later, “I had already cut my hair short.”
While walking on a local beach, Karen received a call from the hospital telling her that she had been assigned to the trial group and would not need chemotherapy.
She said: “How would you describe the initial feeling? An immense sense of relief? Is it like Christmas? It’s definitely a mix of the two.”
Karen underwent radiation therapy and hormone therapy instead of chemotherapy, completing eight years of active treatment.
Almost nine years after her diagnosis, Karen said she no longer feels defined by cancer and has returned to a normal family life. She remains active and enjoys walking and yoga. Participating in the OPTIMA trial “helped me make better decisions to receive targeted and appropriate treatment more quickly, resulting in positive health outcomes.”
sauce:
university college london
