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

LIH and IBBL contribute to the first results of the European project

Analysis of the data obtained from the first 381 patients included in the AURORA research programme have revealed important molecular and clinical features that shed light on metastatic breast cancer (MBC) and its evolution. The detailed results were published on June 28th in Cancer Discovery, a journal of the American Association for Cancer Research.       

AURORA is an international academic research programme based on molecular screening and dedicated to improving the understanding of metastatic breast cancer. Its unique large collection of matched primary and metastatic tumour samples, obtained from patients either upon diagnosis of metastatic disease or after one line of treatment, and high-quality clinical data allow researchers to study the molecular changes that occur when breast cancer first starts to spread, and throughout its evolution.

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 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 metastatic cancers expressed fewer immune-related genes and had a different immune cell composition, which may create a microenvironment more favourable to their development. In addition, patients with hormone receptor-positive (HR+) HER2-negative breast cancer who also had high tumour mutational burden (TMB) in their primary tumours were found to have both shorter overall survival and shorter time to relapse, indicating that TMB is an independent poor prognostic factor. The research team 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.

LIH, and specifically its Clinical and Epidemiological Investigation Centre (CIEC), and IBBL played a central role in the project. CIEC acted as the Luxembourg representative for the study and coordinator between the different study participants, the sponsor (Breast International Group – BIG) and the various Luxembourg institutes involved, namely the Centre Hospitalier de Luxembourg (CHL), the Laboratoire National de Santé (LNS) and IBBL. CIEC’s clinical research associates contributed to the initial phases of the project, such as the feasibility assessment and submission of the necessary documentation to the National Research Ethics Committee (CNER) and to the Ministry of Health for approval, while CIEC nurses were involved in patient screening, inclusion and follow-up, in collaboration with doctors from CHL.

As the biobank of the study, IBBL was involved in the long-term storage of the study samples, as well as contributing to biosepcimen processing including, for instance, RNA extractions.

The 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 significant logistical effort and a valuable resource that could support the generation of hypotheses for new treatment strategies.

We are very proud to have put our expertise in biological sample storage and processing to the service of this large collaborative pan-European study and to have contributed to these first results, which will support the development of novel therapies and ultimately improve patient outcomes”, explains Dr Amélie Gaignaux, Clinical Research Project Manager at IBBL.

The AURORA programme is led by Breast International Group (BIG) in collaboration with the Clinical Trials Support Unit of the Institut Jules Bordet (IJB-CTSU) and Frontier Science (Scotland) Ltd. It was launched by BIG in 2014 and involves over 60 hospitals and cancer centres from 11 European countries. So far, it has included 1,150 patients with advanced (metastatic) breast cancer, and an ambitious plan to include additional patient populations with unmet needs such as triple negative breast cancer is now underway. AURORA is an academic study made possible by generous contributions from the Breast Cancer Research Foundation®, Fondation Cancer (Luxembourg), NIF Foundation, Barrie and Deena Webb, Candriam, Fondation Futur 21, Sogerim, Think Pink Belgium (SMART Fund) and many individual donors. AURORA has also been supported by the Fund Friends of BIG, managed by the King Baudouin Foundation.