First results of ABCSG 51 / AURORA study published
29.06.2021The AURORA program is dedicated to researching the molecular characteristics of locally recurrent / advanced and metastatic breast cancer not amenable to treatment with curative intent. For this purpose, the tumor and blood samples of participants are assessed for tumor heterogeneity, clonal evolution and transcriptional changes using high-throughput sequencing technologies (NGS). In addition, biomarkers of response and resistance to systemic therapies are evaluated with help of genomic and transcriptomic data.
AURORA was launched by BIG (Breast International Group) 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. In Austria, AURORA is coordinated by ABCSG and 18 patients were included in 4 active centers until date. Currently, there is no active enrolment in the study, but if funding for inclusion of further patients is secured, a total of 2000 metastastic breast cancer patients will be included.
The comprehensive analyses of data from the first 381 patients included in the AURORA research programme have now revealed important molecular and clinical features that shed more light on metastatic breast cancer (MBC) and how it evolves. The detailed results have currently been published in Cancer Discovery, a journal of the American Association for Cancer Research under the title “Genomic and transcriptomic analyses of breast cancer primaries and matched metastases in AURORA, the Breast International Group (BIG) molecular screening initiative” [1].
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. Further analyses will focus on deeper understanding of molecular subtypes, clonal evolution, treatment selection, and resistance mechanisms.
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 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 tremendous logistical effort and a valuable resource that could support the generation of hypotheses for new treatment strategies.
Coordinating Investigator of the Study in Austria, Assoz. Prof. PD Dr. Marija Balic, comments on the results: “The AURORA study represents a great international effort to understand metastatic breast cancer. With challenging logistics and public funding more than 1000 patients have been already enrolled in the trial, and their molecular analyses provide a crucial basis for better treatment of metastatic breast cancer patients in future. The first results already provide interesting insights in topics of interest and further planned analyses provide unique opportunity to gather knowledge on molecular processes and establish novel treatment strategies.”
[1] Genomic and transcriptomic analyses of breast cancer primaries and matched metastases in AURORA, the Breast International Group (BIG) molecular screening initiative
Philippe Aftimos, Mafalda Oliveira, Alexandre Irrthum, Debora Fumagalli, Christos Sotiriou, Einav Nili Gal-Yam, Mark E Robson, Justin Ndozeng, Angelo Di Leo, Eva M Ciruelos, Evandro de Azambuja, Giuseppe Viale, Elsemieke D Scheepers, Giuseppe Curigliano, Judith M Bliss, Jorge S Reis-Filho, Marco Colleoni, Marija Balic, Fatima Cardoso, Joan Albanell, Caroline Duhem, Sandrine Marreaud, Dario Romagnoli, Beatriz Rojas, Andrea Gombos, Hans Wildiers, Angel GUERRERO-ZOTANO, Peter Hall, Andrea Bonetti, Karolina Fs Larsson, Martina Degiorgis, Silvia Khodaverdi, Richard Greil, Asgerdur Sverrisdottir, Marta Paoli, Ethel Seyll, Sybille Loibl, Barbro Linderholm, Gabriele Zoppoli, Nancy E Davidson, Oskar Th Johannsson, Philippe L Bedard, Sherene Loi, Susan Knox, David A Cameron, Nadia Harbeck, Maite Lasa Montoya, Mariana Brandão, Andrea Vingiani, Carmela Caballero, Florentine S Hilbers, Lucy R Yates, Matteo Benelli, David Venet and Martine J Piccart
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