Characterization of multifocal breast cancer using the 70-gene signature in clinical low-risk patients – A sub-analysis of the EORTC 10041/BIG 03-04 MINDACT trial

The primary results of the EORTC 10041/BIG 03-04 MINDACT trial were published in 2016 in the prestigious New England Journal of Medicine. The MINDACT database including 6693 patients represents a unique opportunity for knowledge development. Therefore, EORTC evaluated the association between tumour focality and gene expression (the 70-gene signature [70-GS]) as well as the outcome in a large population of early-stage breast cancer patients. These results were recently published in the European Journal of Cancer.

The analysed population out of the MINDACT trial included 3,088 patients with unifocal and 238 patients with multifocal disease and assessed clinically low-risk disease. Clinico-pathological characteristics and gene expression of patients with unifocal and multifocal disease were compared. Subsequently, the association between multifocal disease and the 70-GS was evaluated as well as the association between multifocality and 5-year distant metastasis-free survival (DMFS).

Although current guidelines recommend basing adjuvant systemic breast cancer treatment on the characteristics of the largest lesion disregarding multifocality as an independent prognostic factor, and despite the fact that multifocality has been proven to be associated with an increased incidence of a high genomic risk as per the 70-GS, this study did not demonstrate any significant interaction between multifocality and the 70-GS with respect to survival without distant metastasis in patients regarded as clinical low-risk. However, a prognostic effect of the 70-GS on DMFS in both unifocal and multifocal tumours was observed.

This project was led by Dr Kim Aalders, a research fellow based at the EORTC Headquarters in Brussels. Dr Aalders said “The EORTC fellowship programs provide a unique opportunity for early career investigator to develop skills in clinical and translational research and generate new critical information for patients. The knowledge and scientific rigor I acquired will benefit all my future patients.”

Dr Denis Lacombe, EORTC Director General, emphasizes here “the values of EORTC, an independent clinical research organisation uniquely placed to perform such large international studies like MINDACT, ensuring long term database exploitation for knowledge development, notably through the EORTC fellowship program, a thorough educative program, bringing forward the future generation of clinical investigators.”