Karen Bonham had already cut her hair short. Days from starting chemotherapy, the 64-year-old from Cardiff was bracing for a regimen her doctors considered standard for her type of breast cancer — a large, hormone-sensitive tumour that had spread to two lymph nodes. Then her phone rang. Walking on a local beach, she learned she would not need chemotherapy after all.

The call came courtesy of a gene test called Prosigna, and the trial that produced it could reshape breast cancer treatment worldwide. Results from the OPTIMA trial, presented this week at the American Society of Clinical Oncology’s annual meeting in Chicago, show that more than two-thirds of certain high-risk breast cancer patients can safely skip chemotherapy without increasing their risk of the cancer returning.

What the test measures

Prosigna, made by the diagnostics company Veracyte, measures the activity of 50 genes involved in breast cancer growth. It calculates a “risk of recurrence” score from a tumour tissue sample — even a small diagnostic needle biopsy. Patients scoring 60 or below are classified as low-risk and receive hormone therapy alone; those above 60 get the full regimen of chemotherapy followed by hormone therapy.

The OPTIMA trial enrolled 4,429 patients — women and men aged 40 or older with hormone-sensitive breast cancer, recruited at 171 hospitals across the UK, Norway, Sweden, Australia, New Zealand, and Thailand. Most had cancer that had spread to underarm lymph nodes, placing them at high risk of recurrence. Participants were randomly assigned to either standard treatment or a test-directed group where Prosigna scores determined their therapy.

Of the test-directed group, 68% received a low score. Among those patients, five-year outcomes were nearly identical whether they received chemotherapy or not: 93.7% of those who skipped chemo were alive and recurrence-free, compared with 94.9% of those who received it, according to trial results presented at ASCO. The 1.2 percentage-point difference fell well within the 3% margin that clinicians and patients had agreed was acceptable beforehand.

A statistical analysis suggested that at most 2% of low-scoring patients actually benefit from chemotherapy. For the rest, the treatment adds toxicity without meaningful gain.

The toll of unnecessary treatment

Chemotherapy’s side effects are well documented: fatigue, nausea, hair loss, weakened immunity, fertility problems. Up to 43% of breast cancer survivors experience persistent nerve damage years after treatment, according to research cited by Veracyte. For a treatment that offers little additional benefit to a large subset of patients, those costs are difficult to justify.

Professor Rob Stein, the trial’s chief investigator at the UCL Cancer Institute, said the results mean “many may be spared the physical and emotional burden of chemotherapy and its potential long-term side effects.”

Bonham described the moment she learned she could avoid it as “immense relief” and “like Christmas.” Instead of chemotherapy, she received eight years of radiotherapy and hormone therapy — standard tablets taken for five to ten years that block the hormones fuelling tumour growth. Almost nine years on from her diagnosis, she says she has returned to normal family life.

Who is included — and who is not

Unlike earlier studies that focused mainly on postmenopausal women with limited lymph node involvement, OPTIMA included premenopausal women and patients whose cancer had spread to four or more lymph nodes — groups where treatment guidance had been most uncertain. Outcomes were consistent across all subgroups.

But the findings do not yet apply to patients under 40. A follow-up phase is planned, but results are several years away, according to UCL. Too few men participated to draw firm conclusions for that group either.

A test that works, but for whom?

Prosigna has a practical advantage over some competing genomic tests: it can be run on standard laboratory equipment, including within the UK’s National Health Service. Researchers estimate that more than 5,000 NHS patients per year could avoid chemotherapy as a result.

Yet a test that works is not the same as a test available everywhere. The trial’s results will now go to bodies like the National Institute for Health and Care Excellence (NICE) to determine wider NHS access and cost-effectiveness. The global picture is even less clear — the study was conducted almost entirely in well-resourced healthcare systems, and how quickly the approach could reach patients in lower-income countries remains an open question.

Breast cancer is the most commonly diagnosed cancer worldwide. The OPTIMA trial offers millions of those patients something rare: the possibility of less treatment, not more, without trading away survival. Turning that possibility into universal access is the harder work ahead.

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