Long-term follow-up of the MINDACT trial confirmed that the MammaPrint 70-gene signature test can identify breast cancer patients who are unlikely to benefit from chemotherapy, researchers reported in The Lancet Oncology.
The researchers found that older patients with high clinical risk but low genomic risk have “excellent” 8-year distant metastasis-free survival when treated with endocrine therapy alone.
The phase 3 MINDACT trial (ClinicalTrials.gov Identifier: NCT00433589) enrolled 6693 patients. Most had luminal HER2-negative, hormone receptor (HR)–positive breast cancer (80.7%). The remaining patients had luminal HER2-positive (7.5%), triple-negative (9.6%), or nonluminal HER2-positive breast cancer (2.0%).
The patients were assigned to chemotherapy according to their clinical risk and genomic risk, as determined by the MammaPrint 70-gene signature test. Patients with high clinical and genomic risk received chemotherapy, while patients with low clinical and genomic risk received only endocrine therapy.
Patients with high clinical risk but low genomic risk were randomly assigned to receive endocrine therapy with chemotherapy (n = 749) or without it (n = 748). This was the intention-to treat population.
The median follow-up was 8.7 years. In the intention-to treat population, the 8-year estimate for distant metastasis-free survival was 92.0% for the chemotherapy arm and 89.4% for the no-chemotherapy arm (hazard ratio [HR], 0.66; 95% CI, 0.48–0.92).
An exploratory analysis that included only patients with HR-positive, HER2-negative disease (n = 1358) showed that the effects of chemotherapy differed by age.
In patients 50 years of age and younger, the 8-year distant metastasis-free survival was 93.6% with chemotherapy and 88.6% without chemotherapy. The absolute difference was 5.0 percentage points — a clinically relevant threshold.
In patients older than 50 years, the 8-year distant metastasis-free survival was 90.2% with chemotherapy and 90.0% without it. The absolute difference was 0.2 percentage points.
“[T]he updated results of MINDACT indicate that relying on the genomic signature to forego adjuvant chemotherapy is safer in older women with a high clinical risk than in younger women,” the study authors wrote.
The authors hypothesized that the potential benefit of chemotherapy in younger women might be linked to chemotherapy-induced ovarian function suppression, but further study is needed.
Disclosures: This research was funded by the European Commission Sixth Framework Programme. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Piccart M, van’t Veer LJ, Poncet C, et al. 70-gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age. Lancet Oncol. 2021;22(4):476-488. doi:10.1016/S1470-2045(21)00007-3