An analysis of the MINDACT trial confirms that the 70-gene signature (MammaPrint) keeps its value in women over 50 with early-stage hormone-receptor-positive breast cancer and clinically high-risk features such as large tumours, grade 3 disease or up to three involved nodes: distant metastasis-free survival at eight years remains high without chemotherapy.
What was known
In women over 50 with stage I-II hormone-receptor-positive, HER2-negative breast cancer, adjuvant chemotherapy can be safely omitted when the 70-gene signature indicates low risk. That evidence, however, came mainly from the overall trial population. It was still unclear what happens when a low-risk genomic result coexists with features that would be considered high risk on clinical grounds alone: a tumour larger than two centimetres, grade 3 histology or involved axillary nodes. That uncertainty complicates the decision in the clinic.
What this study adds
This is an exploratory subgroup analysis using data from the MINDACT trial. The authors selected women over 50 with primary stage I-II hormone-receptor-positive, HER2-negative breast cancer and a clinically high-risk profile plus a low-risk genomic signature; in the original trial they were randomly assigned to have the chemotherapy decision based on clinical criteria or on the genomic result. The primary endpoint was distant metastasis-free survival at eight years.
Main results
A total of 868 patients with high clinical and low genomic risk were analysed, with a median follow-up of 8.7 years. Of these, 490 (56.5%) had tumours larger than 2 cm, 232 (26.7%) had grade 3 tumours and 406 (46.8%) had one to three involved nodes. Eight-year distant metastasis-free survival in the group that did not receive adjuvant chemotherapy was 87.9% for tumours larger than 2 cm, 91.3% for grade 3 tumours and 89.6% for patients with nodal involvement. The absolute eight-year gain from chemotherapy was minimal: 1.2% for larger tumours, 0.7% with involved nodes and no appreciable advantage (−2.2%) for grade 3 tumours.
What it means
The findings support the prognostic value of the 70-gene signature also in these subgroups of apparently high clinical risk: adding chemotherapy did not translate into a meaningful improvement in eight-year distant metastasis-free survival. The authors stress that this is an exploratory analysis and not a trial designed to answer this question. Even so, the practical message is that clinical features alone may overestimate a tumour’s true risk.
Reading from the breast unit
Deciding whether to give adjuvant chemotherapy is one of the points where the quality of a breast unit is most at stake: avoiding overtreatment without giving up safety. This work reinforces that genomic information helps refine that decision even in tumours with unfavourable clinical features, always within a multidisciplinary meeting and with the signature embedded in the care pathway.
Reference: Gielen RCAM, Poncet C, van ‘t Veer LJ, Rubio IT, Delaloge S, Pierga JY, et al. 70-gene signature MammaPrint for early-stage HR-positive, HER2-negative breast cancer: Outcome in the MINDACT trial for key clinical-pathological high-risk subgroups. European Journal of Cancer, 2026. https://doi.org/10.1016/j.ejca.2026.117044
