Promising results for the ultra-low risk patient group in latest MINDACT analysis

The MINDACT (EORTC 10041/BIG3-04) study, a multicentre, randomised phase 3 clinical trial, aims to identify those women with early-stage breast cancer who can be spared chemotherapy after surgery through the use of a genomic and clinical risk assessment. Between 2007 and 2011, 6693 patients aged 18 to 70 whose cancer had either not spread to the lymph nodes under the arm, or to no more than three nodes, were enrolled to the trial, which was carried out in 112 institutions in nine European countries.

The latest sub-group analysis, published recently in the Journal of Clinical Oncology* looked at the 15% of patients who had an ultra-low genomic risk of recurrence based on the 70-gene signature MammaPrint. After a median follow-up of 8.7 years, 99% of these patients had not died from their disease, and their risk of cancer spreading to other parts of the body (distant metastasis) was significantly less than for patients with low-risk tumours. Patients with ultra-low risk tumours had an excellent prognosis regardless of the result of their clinical risk assessment.

Of the ultralow-risk patients, 67% were aged 50 years or more, and 99% were estrogen receptor (ER)-positive. Systemic therapy was received by 84% of patients (69% endocrine therapy (ET), 14% endocrine therapy plus chemotherapy, 1% other) and 16% received no adjuvant systemic treatment.

“Although trials have shown that gene signatures can be used to identify subgroups of patients who can safely be spared chemotherapy, current guidelines still include the use of ET in all hormone receptor positive patients, even those at very low risk” said Dr Josephine Lopes Cardozo, from the Netherlands Cancer Institute and EORTC. “ET side effects are often underestimated, and, as a result, adherence to the treatment is poor, with only half of all patients finishing a five-year course. Our analysis of ultra-low risk patients shows that these patients might be candidates for further reduction of treatments such as ET.”

The investigators hope that the ultra-low risk gene signature will be used in future trials investigating the de-escalation of ET in order to achieve a better balance between benefit and harm. Findings from earlier studies have suggested that the introduction of population-based screening programmes has led to an increase of tumours with low-risk and ultra-low risk molecular profiles, and that these are over-represented within screen-detected cancers. “Being able to identify these patients who may have a limited benefit from ET could help to personalize treatment by reducing treatment durations or completely omitting ET and ultimately preventing overtreatment,” says Dr Lopes Cardozo. “This would have benefits not only for patients, but also save money for healthcare systems.”

*DOI: 10.1200/JCO.21.02019