While research has made great strides in recent decades to improve and significantly extend the lives of patients with early breast cancer, research initiatives focusing on patients with metastatic disease have not been equally successful. In this context, BIG shifted its focus substantially in 2013, building its flagship programme AURORA and developing several clinical trials for this disease.
AURORA is an innovative, international programme set up to significantly improve our understanding of metastatic breast cancer, so that one day better treatments, and potentially cures, can be offered to patients with this disease. In total over 1000 women and men from about 80 hospitals across Europe are expected to take part in this programme that was launched in April 2014. Over time, BIG hopes to expand the programme well beyond Europe to involve even more patients.
Currently, 65 hospitals in 10 different countries are taking part in AURORA and are already recruiting patients. See the list of activated sites.
Today’s technology enables us to characterise cancer on the genetic level in great detail. This heralds tremendous promise with regard to understanding the genetic changes (aberrations) within tumours over time, and their genetic heterogeneity. For breast cancer in particular, many recent studies – using a type of genetic analysis referred as next generation sequencing – have uncovered a large number of genetic aberrations in tumours that occur at a low frequency. In some cases, experimental drugs being developed could be used as targeted treatment against these aberrations, and potentially lead to extending patients’ lives significantly.
There is increasing evidence to demonstrate that when breast cancer spreads (1 breast cancer patient out of 3 develops metastases), it acquires genetic aberrations that differ from those that were present when the disease first appeared. In addition, different resistance mechanisms to treatments may emerge over time. Obtaining biopsies from metastatic breast tumours and comparing them to biopsies taken at the time the breast cancer first occurred will help uncover mechanisms of treatment resistance – but also why some patients respond exceptionally well to treatment.
Recently many individual hospitals, private laboratories and even national governments have established molecular screening initiatives that aim to provide physicians and patients with a report of all the genetic aberrations found in a patient’s tumour. While these initiatives may be well intentioned, they have major limitations because they generate results that might lose their potential and impact if not interpreted in a properly structured clinical setting involving multiple cancer specialists and geneticists.
Moreover, the use of modern technologies is likely to result in breast cancer being classified into ever smaller genetic sub-types. This means that clinical trials aiming to test new treatments for these sub-types cannot be run by individual hospitals or even on national levels; instead, they will require well-organized, international collaboration to be able to enrol enough patients to generate meaningful study results, something that BIG is well positioned to do.
In practice, AURORA consists of collecting biopsy samples from both primary and metastatic tumours. Initially they will be subjected to molecular profiling with a panel of more than 400 cancer-related genes. Plasma and blood samples will also be collected, and any samples not analysed immediately will be stored in an independent bio-repository to enable future research.
An innovative bioinformatics platform has been developed to support the collection of AURORA data. These data are being collected in a way that will allow sharing and collaborating in the context of other initiatives started by researchers in North America. Governed by a Steering Committee of renowned metastatic breast cancer and molecular experts as well as patient advocates, critical work for AURORA will be carried out by its Molecular Advisory Board, involving cancer geneticists, pathologists, bioinformaticians and oncologists.
How will AURORA benefit patients?
AURORA is expected to enable us to understand both why breast cancer metastasises and why some patients respond poorly to standard treatment, while others respond very well. Whenever possible, patients participating in AURORA will be offered to participate in a clinical trial testing new and promising drugs that target the specific genetic characteristics of their tumours. The hope is that AURORA will benefit patients by leading us in the future to both better treatments and to finding cures for the women and men affected by this disease.
AURORA is being conducted with the Breast European Adjuvant Study Team and Frontier Science Scotland. It is made possible in part by generous grants from the Breast Cancer Research Foundation®, the Fondation Cancer (Luxembourg), the National Lottery (Belgium), NIF Trust and individual donors. AURORA is also being carried out with the support of the Fund Friends of BIG, managed by the King Baudouin Foundation.