The first results of the European AURORA study, which analysed data from 381 patients, have revealed important molecular and clinical features of metastatic breast cancer and how it develops. The study has been published in the American Association for Cancer Research journal, Cancer Discovery, and Dr. Joan Albanell, head of the Medical Oncology Service at Hospital del Mar and director of the Cancer Research Programme at IMIM, is one of the authors.
The study has provided a clear and comprehensive map of the genomic profiles for the main subtypes of metastatic breast cancer and the changes that occur between initial disease and metastasis. The results indicate the presence of many genomic alterations, in about half of the cases, that can be targeted pharmacologically with drugs, many of which are currently experimental. They also reveal an immune environment that is unfavourable to metastatic disease, which should be the subject of innovative research to understand and reverse this environment.
Dr Albanell notes that "The AURORA results give us information on the genomic changes that occur between early breast cancer and metastatic relapse. In this phase, in almost half of the cases, we observe molecular alterations that can be attacked pharmacologically. Moreover, metastases grow in an environment consistent with a more immunosuppressed state than primary tumours." For that reason, "This information should serve as the basis for further research into the ecology of metastatic breast cancer and for the design of new clinical trials", he concludes.
The researchers studied samples of metastatic breast tumours from newly diagnosed patients or after their first treatment, allowing them to examine the molecular changes that occur when breast cancer begins to spread and during the progression of metastatic disease. This has allowed them to identify which of these changes are most common in these samples. This includes mutations in driver genes, present in 10% of the samples, and in their copies, found in 30% of the samples. This may lead to the development of new treatment strategies for these patients.
AURORA
The AURORA programme has resulted in the largest RNA sequencing database for metastatic breast cancer. The analysis shows that in two out of three cases the breast cancer subtype switches between primary and metastatic disease, usually to a more aggressive form. Furthermore, patients with HER2-negative breast cancer who also have a higher mutational burden in the primary tumour have a shorter survival period and time to relapse, indicating that this characteristic may be a factor in a worse prognosis. Finally, the researchers found that half of the patients have molecular changes that could be combined with existing targeted therapies, highlighting the potential impact of molecular screening in the management of this disease.
Reference article
Aftimos P, Oliveira M, Irrthum A, Fumagalli D, Sotiriou C, Nili Gal-Yam E, Robson ME, Ndozeng J, Di Leo A, Ciruelos EM, de Azambuja E, Viale G, Scheepers ED, Curigliano G, Bliss JM, Reis-Filho JS, Colleoni M, Balic M, Cardoso F, Albanell J, Duhem C, Marreaud S, Romagnoli D, Rojas B, Gombos A, Wildiers H, Guerrero-Zotano A, Hall P, Bonetti A, Larsson KF, Degiorgis M, Khodaverdi S, Greil R, Sverrisdottir A, Paoli M, Seyll E, Loibl S, Linderholm B, Zoppoli G, Davidson NE, Johannsson OT, Bedard PL, Loi S, Knox S, Cameron DA, Harbeck N, Lasa Montoya M, Brandão M, Vingiani A, Caballero C, Hilbers FS, Yates LR, Benelli M, Venet D, Piccart MJ. Genomic and transcriptomic analyses of breast cancer primaries and matched metastases in AURORA, the Breast International Group (BIG) molecular screening initiative. Cancer Discov. 2021 Jun 28:candisc.1647.2020. doi: 10.1158/2159-8290.CD-20-1647. Epub ahead of print. PMID: 34183353.
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