AURORA (BIG 14-01)

Intro text: 

Aiming to understand the molecular aberrations in metastatic breast cancer

(public name: Metastatic Breast Cancer GPS)

AURORA is an international, academic research programme that uses molecular screening technology to decode the genetic characteristics of a tumour and identify the changes (genetic aberrations) that drive disease evolution over time, in patients with recurrent or locally relapsed metastatic breast cancer.

AURORA will address an important unmet medical need in metastatic breast cancer, for which current treatment options are limited and are usually based on the clinical-pathological characteristics of the primary tumour rather than on the characteristics of the tumour once it has spread.

Decoding the genes of cancer

Thanks to the highly advanced technologies available today, such as next-generation sequencing analysis, researchers are able to characterise tumours on the genetic level in great detail. 

Several studies suggest that when breast cancer spreads, it develops genetic aberrations that differ from those present when the disease first appeared. In addition, different resistance mechanisms to treatments may emerge over time.

By analysing the molecular profile of pre-collected tissue from the primary tumour, and comparing it to tissue from the metastatic tumour and blood samples, scientists involved in AURORA aim to follow disease evolution over time and better understand the biological events driving cancer progression. They also hope to uncover the various mechanisms of resistance or response to standard treatments and targeted therapies.

AURORA could open new treatment strategies leading to prolonged disease control in patients affected by metastatic breast cancer.

Moreover, by developing the necessary infrastructure for a molecular screening programme designed to complement clinical trials done on an international scale, it is hoped that patients with rarer genetic aberrations could be offered experimental and promising drugs that target the characteristics of their tumours.

The huge amount of collected information will also enable new hypotheses to be generated for future research.

The initial results of AURORA, which report on the first 381 patients included out of a planned total of 1,000, were presented at the ESMO Breast Cancer Congress held on 2-4 May 2019 in Berlin, Germany. By analysing solid and liquid biopsies from these patients, researchers were able to identify specific genetic aberrations present in excess in metastases that may be correlated with the spread of cancer and increased resistance to standard treatments.

In addition, the investigators of the programme estimate that in almost 50% of cases the genetic aberrations identified could provide treating oncologists with additional information useful for patients (for example, patients could be considered for clinical trials testing new drugs targeting specific genetic aberrations).

"Liquid biopsies" (tests done on blood to look for cancer cells) could have an important role in characterising and monitoring the disease, since, in some patients, analysis of circulating tumour DNA revealed genetic aberrations not observed in the tumour biopsy.

Analyses of the tumour immune environment – looking at how cells from our immune system interact with cancer cells – are also underway and will be presented at future congresses.

Clinical data and biological samples (blood and tumour tissue) are collected from all patients and analysed based on a panel of 411 cancer-related genes.

A unique aspect of AURORA is that these genetic tests are done on samples available from the primary tumour, as well as on samples taken after the cancer has metastasised.

The results of each patient are analysed by the AURORA Molecular Advisory Board, which delivers a report to the treating physician.

If a genetic aberration is found, a clinical trial testing a new drug that targets that aberration may be proposed to the patient (if the physician finds it appropriate). If no drug or clinical trial is available, or if no aberration is found, the physician chooses the best available standard treatment for the patient.

Whole exome sequencing analysis will be performed on tumour materials from patients whose disease responded either exceptionally well or poorly to standard treatment. Exome analysis looks at a subset of genetic information and aims to identify the mechanisms that drive these exceptional cases.  

All patients participating in AURORA will be followed-up every 6 months and for up to 10 years.

A bioinformatics platform has been developed to support the collection of data from the patients enrolled in AURORA.

Women and men aged 18 and older who have been newly diagnosed with metastatic breast cancer for which they have received no more than one course of treatment. Participation requires primary and metastatic tumour tissue as well as blood to be available for genetic testing.

The initial overall recruitment goal of 1,000 patients was reached on 19 August 2020. It has been decided to keep the recruitment open with the aim to include 1,000 additional patients if funding is secured.

The programme was set up and launched by the Breast International Group, which is also the legal sponsor.

It is coordinated by BIG Headquarters, in collaboration with the Institut Jules Bordet’s Clinical Trials Support Unit (IJB/CTSU) (formerly BrEAST) and Frontier Science Scotland (FSS).

Recruitment of patients started in 2014 and is still ongoing.

The initial results of AURORA, which report on the first 381 patients included out of a planned total of 1,000, were presented at the ESMO Breast Cancer Congress held on 2-4 May 2019 in Berlin, Germany.

About 60 hospitals located in more than 10 different countries across Europe are participating in the programme, which involves 11 BIG member groups.

AURORA is made possible in part by generous grants from the Breast Cancer Research Foundation® (BCRF) as the main funder, Fondation contre le Cancer (Belgium), Fondation Cancer (Luxembourg), National Lottery (Belgium), NIF Foundation, Barrie and Dena 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. Identifier: NCT02102165