First results of the European AURORA study: towards a better understanding of the molecular changes driving metastatic breast cancer

28 Jun 2021
First results of the European AURORA study: towards a better understanding of the molecular changes driving metastatic breast cancer

AURORA is an international academic research programme based on molecular screening and is dedicated to improving our understanding of metastatic breast cancer.

It is unique with its large collection of matched primary and metastatic tumour samples, obtained from patients either at the diagnosis of metastatic disease or after one line of treatment, as well as its high-quality clinical data collection.

Using these samples and data, researchers can study the molecular changes that occur when breast cancer first starts to spread, and throughout the evolution of metastatic disease.

So far, researchers have identified molecular changes that are more common in metastatic samples.

These include mutations in driver genes (in 10% of the samples) and in copy number variations (in 30% of samples). These findings could lead to the future development of new treatment strategies for patients with MBC.

The programme has already generated what is to our knowledge the largest dataset of RNA sequencing (RNAseq) in MBC.

The analyses of RNAseq data from paired primary and metastatic samples from the same patients showed that, in 36% of the cases, the breast cancer intrinsic subtype changes between the primary and the metastatic disease, usually towards a more aggressive form. This may have treatment implications and deserves further assessment.

The analyses also indicated that metastases expressed fewer immune-related genes and had a different immune cell composition, which may create a microenvironment more favourable to the development of metastases.

The analysis of how long patients survived with the disease showed that those with hormone receptor-positive (HR+) HER2-negative breast cancer who also had high tumour mutational burden (TMB) in their primary tumours had both shorter overall survival and shorter time to relapse, indicating that TMB is an independent poor prognostic factor.

Finally, researchers also found that more than 50% of patients had molecular changes that could be matched with existing targeted therapies, highlighting the potential impact of molecular screening in the management of MBC.

These findings will be further validated in the full cohort of AURORA patients. To date, AURORA is the largest molecular screening programme involving paired biopsies, blood samples, and a rich set of clinical and molecular data collected longitudinally from patients with MBC.

It represents a tremendous logistical effort and a valuable resource that could support the generation of hypotheses for new treatment strategies.

“This study offers a unique opportunity to generate robust findings that will help us better understand the evolution of metastatic breast cancer, which is still the leading cancer-related cause of death among women worldwide.

True to its name, AURORA will bring light to the dark landscape of advanced breast cancer”, says Dr Martine Piccart, the initiator of the study.

“AURORA is a large collaboration effort to which patients contributed massively with their time and samples.

The impact of the clinico-genomic database and rich biobank will empower future research on metastatic breast cancer”, explains Dr Philippe Aftimos, Co-Principal Investigator of the programme and Clinical Trials Development Leader at the Institut Jules Bordet in Brussels, Belgium. 

“The knowledge that is being generated within AURORA paves the way towards the development of new treatment strategies for patients with metastatic breast cancer.

We are firmly committed to continue this effort so that our patients may live longer and better in the near future”, says Dr Mafalda Oliveira, Co-Principal Investigator of AURORA, Clinical Investigator at the Vall d’Hebron Institute of Oncology in Barcelona, Spain, and member of the Executive Board of the SOLTI Breast Cancer Research Group.

Source: The Breast International Group (BIG)