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

Abstract

Background The MINDACT trial showed excellent 5-year distant metastasis-free survival of 94•7% (95% CI 92•5-96•2) in patients with breast cancer of high clinical and low genomic risk who did not receive chemotherapy. We present long-term follow-up results together with an exploratory analysis by age.Methods MINDACT was a multicentre, randomised, phase 3 trial done in 112 academic and community hospitals in nine European countries. Patients aged 18-70 years, with histologically confirmed primary invasive breast cancer (stage T1, T2, or operable T3) with up to three positive lymph nodes, no distant metastases, and a WHO performance status of 0-1 were enrolled and their genomic risk (using the MammaPrint 70-gene signature) and clinical risk (using a modified version of Adjuvant! Online) were determined. Patients with low clinical and low genomic risk results did not receive chemotherapy, and patients with high clinical and high genomic risk did receive chemotherapy (mostly anthracycline-based or taxane-based, or a combination thereof). Patients with discordant risk results (ie, patients with high clinical risk but low genomic risk, and those with low clinical risk but high genomic risk) were randomly assigned (1:1) to receive chemotherapy or not based on either the clinical risk or the genomic risk. Randomisation was done centrally and used a minimisation technique that was stratified by institution, risk group, and clinicalpathological characteristics. Treatment allocation was not masked. The primary endpoint was to test whether the distant metastasis-free survival rate at 5 years in patients with high clinical risk and low genomic risk not receiving chemotherapy had a lower boundary of the 95% CI above the predefined non-inferiority boundary of 92%. In the primary test population of patients with high clinical risk and low genomic risk who adhered to the treatment allocation of no chemotherapy and had no change in risk post-enrolment. Here, we present updated follow-up as well as an exploratory analysis of a potential age effect (≤50 years vs >50 years) and an analysis by nodal status for patients with hormone receptor-positive and HER2-negative disease. These analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00433589, and the European Clinical Trials database, EudraCT2005-002625-31. Recruitment is complete and further long-term follow-up is ongoing.

Top 3 abstracts concerning hormone-receptor-positive early breast cancer

“…Hence, the benefit from adjuvant chemotherapy in premenopausal women was reproduced in RxPONDER. Similar results were also observed in an exploratory analysis of the MINDACT trial were an absolute chemotherapy benefit in distant metastasisfree survival (DMFS) of 5.0% was seen after 8 years of follow-up in patients ≤ 50 years with high clinical risk but low genomic risk according to MammaPrint [8]. In all of these three trials the rate of patients receiving OFS was low (between 3 and 16% in the different treatment arms) it is possible that this age dependent effect is a result of chemotherapy-induced OFS rather than of direct cytotoxicity.…”

The WISDOM study: a new approach to screening can and should be tested

“…There are ongoing efforts to improve our diagnostic tools to identify ultralow risk tumors (those with minimal if any risk for metastasis) at the time of diagnosis, to reduce overtreatment [25]. In the treatment of breast cancer, we are increasingly targeting therapy with the intent to provide more effective treatment for those at highest risk of recurrence, and to de-escalate therapy in those with lowest risk [26,27]. These changes are occurring in every discipline involved with breast cancer treatment.…”

Molecular Testing in Breast Cancer

“…However, the benefit of adjuvant chemotherapy seems to be age dependent: an underpowered exploratory analysis showed that c-riskehigh/griskelow patients aged <50 years might gain more benefit from adjuvant chemotherapy. 19,20 Of note, this prospective clinical trial provided strong evidence for the prognostic value of the MammaPrint test, but was not statistically powered to support its predictive value.…”