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1 April 2019 -

The AURORA project in metastatic breast cancer research

The AURORA project in metastatic breast cancer

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AURORA Europe and US are two of the most ambitious programmes ever carried out to improve understanding of metastatic breast cancer [1] and have been established through the BIG-NABCG collaboration, funded by the BRCF as a result of the sale of Evelyn Lauder’s jewellery.

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“What astonishes me about AURORA is the enthusiasm with which all the international investigators of note have come together to study the molecular biology of metastatic breast cancer and identify potential targets to prevent tumour spread, in a way that has never been attempted before,” says Norton. “There’s a lot to be said for competition in research, but AURORA is showing the value of cooperation so that everyone can benefit,” Dr Larry Norton, Founder and Scientific Director of BCRF, adds.

AURORA is two parallel but closely linked initiatives, run respectively in North America and in Europe. AURORA in Europe is analysing primary and metastatic biopsy samples from approximately 1,000 patients with metastatic breast cancer and subjecting them to next generation sequencing of a panel of cancer-related genes. In addition, plasma samples are collected at study entry, every six months and at each disease progression. All clinical data are collected from these patients, including successive treatments and responses, and patients are followed up for 10 years.

By performing the sequencing, we hope to gain a better understanding of the clonal evolution of the disease, and which clones become dominant, to help us understand why we are not curing metastatic breast cancer so that, hopefully, we can change this,” says Professor Martine Piccart,BIG co-founder and chair.

The strength of AURORA Europe is that samples are collected from each patient at various timepoints throughout the course of the disease. This provides a unique opportunity to study tumour evolution and find molecular changes associated with disease progression and treatment sensitivity or resistance.

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Alongside sequencing of a panel of cancer genes, the results of which are provided in real-time to the treating physician, the European AURORA programme also performs RNA and circulating tumour DNA sequencing, generating a comprehensive molecular portrait of each breast cancer.

Patients taking part in the European AURORA programme will be treated at the discretion of their physician according to local practice or depending on the molecular profile of their tumour sample, directed to innovative clinical trials of molecularly targeted agents.

To date AURORA Europe has generated molecular data from more than 600 patients with metastatic breast cancer. The first aggregated results of this programme will be presented this year.

The AURORA US programme is more focused on in-depth analysis of molecular changes in breast cancer over time, without the intention of using results to assign patients to clinical trials. Davidson explains that there are two distinct sub-studies within the US initiative. This first is a retrospective analysis of patients with metastatic breast cancer who very generously donated multiple tissue samples from all metastatic sites for immediate collection after they died. Researchers went back to existing tumour banks to find and study primary breast tumour samples alongside these metastatic samples and appropriate clinical data.

“This has enabled us to study the original tumour and the attributes of metastases in brain, lung, liver and bone to get a better idea of how primary and metastatic tumours change and what drives those metastases to grow,” says Dr Nancy Davidson, Senior Vice President and Director of the Clinical Research Division at the Fred Hutchinson Cancer Research Center in Seattle, USA, and co-chair of the BIG-NABCG Coordinating Group.

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All the tissue samples for this part of the study have now been collected for analysis of DNA, RNA and methylation abnormalities and initial results are expected in 2019.

In the second, prospective part of AURORA US, which will soon get underway, several hundred women with metastatic disease undergoing tissue biopsy for clinical purposes will be asked to donate part of their sample to AURORA US. Researchers will again try to match patients’ primary and metastatic samples so they can identify disease drivers and, in this study, will follow their progress – clinically and through biopsies – over time.

The reference laboratories for the biopsy analysis will be those which took part in The Cancer Genome Atlas study which led to the characterisation of many different types of cancer, and the clinical work will be done through the Translational Breast Cancer Research Consortium (TBCRC) of 19 academic centres in the US.

Davidson points to the huge effort needed to get this study underway, and the importance of the advocate community who have ensured relevant questions are asked and helped raise awareness of the importance of the research.

“I’m very excited about the scientific questions we are attempting to answer, and the laboratories we’ve brought together in our clinical trial consortium. It’s taken longer to bring all this together than I may have hoped but this reflects the complexity of what we’re trying to do, bringing together nearly 20 different institutions,” she says.

Reference
1. Cardoso F, Bartlett JMS, Slaets L et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Ann Oncol. 2018 Feb 1;29(2):405-417.