The decision on whether or not to give chemotherapy after breast cancer surgery is always a difficult one. Because the treatment can have serious side effects, some of them long-term, there is sometimes a risk that its use may do more harm than good. The MINDACT (EORTC 10041/BIG3-04) study, a multicentre, randomised phase 3 clinical trial, aimed to provide an answer to this question, specifically in women with early-stage breast cancer where the cancer had either not spread to the lymph nodes under the arm, or to no more than three nodes. Between 2007 and 2011, 6693 patients aged 18 to 70 were enrolled to the trial, which was carried out in 112 institutions in nine European countries.
Women at low clinical and genomic risk received no chemotherapy, whereas those at high risk for both did. Patients with discordant risk results were randomly assigned to receive chemotherapy or not based either on the genomic risk (determined by the 70-gene signature MammaPrint) or the clinical risk (determined by the risk prediction model Adjuvant! Online). After a median follow-up of five years, the primary analysis showed that patients who were classified as high clinical risk and low genomic risk who did not receive chemotherapy had a 5-year distant metastasis-free survival of 94.7%, a result in line with the primary hypothesis of the trial.
A further analysis at a median 8.7 years of follow-up is published on 12th of March in The Lancet Oncology*. The updated results of the primary analysis confirm the previous results: with more than 90% patients with at least 5 years of follow-up, the 5-year distant metastasis-free survival rate is now estimated to be 95.1% in the primary test population.
For the 1497 women who were at high clinical but low genomic risk, distant metastasis-free survival at 8 years was slightly higher (2.6%) in those who received chemotherapy (749 women) as compared to those who did not receive chemotherapy (748).
There were important differences in results between age groups. For women younger than 50 years the benefit of chemotherapy is present (5%), perhaps because it suppresses ovarian function as an indirect mechanism of action. But in women over 50 years old our results further confirm our earlier conclusion that women with early breast cancer at clinical high but genomic low risk can continue to be spared adjuvant chemotherapy (benefit 0.2%).
“More research is definitely needed for the younger women,” said Principal Investigator Professor Martine Piccart, from the Institut Jules Bordet and cofounder of the Breast International Group (BIG), Brussels, Belgium.
“Our findings will enable us to give individual patients better information about the risks and benefits of adjuvant chemotherapy, and allow them to play their part in making informed decisions on their treatment.
“We are extremely proud to have partnered with the EORTC and BIG on the landmark MINDACT trial, ” said William Audeh, MD, MS, Chief Medical Officer at Agendia. “The results seen in the long term follow-up data reinforce the immense effect the trial will have in advancing more effective treatment planning for patients with breast cancer. The study continues to produce meaningful clinical information on the de-escalation of treatment while encouraging us to conduct further research in additional patient populations to better understand the role of genomic information.”
Professor Michail Ignatiadis, the new chair of the EORTC Breast Cancer Group explained that the EORTC Breast Cancer Group has a long tradition on conducting practice changing trials. “The updated analyses of the MINDACT trial will help many postmenopausal women with breast cancer to avoid unnecessary adjuvant chemotherapy. The MINDACT trial exemplifies the new focus of the Group on embracing innovation in order to deliver precision medicine”, he said.
Paper: Piccart, M. et al. 70-gene signature as an aid to treatment decisions in early breast cancer: updated results of the Phase 3 randomized MINDACT trial. Lancet Oncology Journal March 2021; Vol 22; Number 3; Access online here.