The comprehensive analyses of data from the first 381 patients included in the AURORA research programme have revealed important molecular and clinical features that shed more light on metastatic breast cancer (MBC) and how it evolves. The detailed results have just been published in Cancer Discovery, a journal of the American Association for Cancer Research.
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 favorable 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 est le plus grand programme de test moléculaire impliquant des biopsies appariées, des échantillons sanguins et un ensemble important de données cliniques et moléculaires recueillies de manière longitudinale auprès de patients souffrant d’un cancer du sein métastatique 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”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”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”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
The burden of metastatic breast cancer
It is difficult to know exactly how many cases of breast cancer will eventually metastasize to other parts of the body, but a recent estimate puts this at about 30%2. This advanced form of the disease is responsible for the great majority of breast cancer deaths.
MBC is more difficult to treat and currently remains essentially incurable, and whilst some individuals live much longer than others with the disease, we do not understand why.
In 2020 approximately 685,000 people in the world died from breast cancer1.
AURORA: a large academic research study
AURORA 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, and an ambitious plan to include additional patient populations with unmet needs such as triple negative breast cancer is now underway.
“This pan-European academic study exploring the genomics of metastatic breast cancer is a testimony to the commitment of patients, researchers and clinicians, and the not-for-profit funding bodies and individual donations that have made it possible. In particular, we are grateful for the major support we receive from the USA-based charity Breast Cancer Research Foundation, which shares our vision and supports a sister programme in the USA.”Prof David Cameron, BIG Chair
The AURORA programme is being led by BIG in collaboration with the Clinical Trials Support Unit of the Institut Jules Bordet (IJB-CTSU) and the Frontier Science (Scotland) Ltd.
AURORA is a purely academic study made possible by generous contributions 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.
- 1,150 women and men with advanced (metastatic) breast cancer have already been enrolled in AURORA
- About 30,000 blood and tumour tissue samples will be collected in total
- 411 genes are being analysed in primary tumours and in metastatic tumours
- 11 countries are involved (Belgium, Germany, Iceland, Italy, Luxembourg, Portugal, Spain, Sweden, Switzerland, United Kingdom and Austria)
- +60 hospitals are participating in the study
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- Sung H, Ferlay J, Siegel RL et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
- Ross C, Szczepanek K, Lee M et al. The genomic landscape of metastasis in treatment-naïve breast cancer models. PLoS Genet 16(5): e1008743. May 28, 2020 https://doi.org/10.1371/journal.pgen.1008743