AURORA: impact of age on genetic and transcriptional landscape of advanced breast cancer

The AURORA program is an initiative that is led by the Breast International Group (BIG) that aims at unravelling the complexity of metastatic breast cancer. To this end, comprehensive multi-omics analyses were performed on matched primary and metastatic tumour samples of 1157 patients from 11 European countries. This allows a comparison of the tumour biology at diagnosis and in a metastatic phase. This information is subsequently complemented by liquid biopsies taken during treatment and at disease progression, and with clinical information across multiple treatment lines. For his presentation at ESMO 2024, Prof Dr Gabriele Zoppoli (University of Genoa and IRCCS Policlinico San Martino, Genoa, Italy) used data from the AURORA trial to evaluate the impact of age on the genetic and transcriptional make-up of breast cancer. In this video, Prof Zoppoli and Prof Dr Philippe Aftimos (Institut Jules Bordet, Brussels, Belgium) discuss the outcomes of this analysis.

For this analysis, a total of 830 cases (1,333 samples) were assessed. Interestingly, a younger age at the time of the metastatic breast cancer diagnosis was correlated with primary nodal status and grade, whereas a primary lobular histology was more common among patients with an advanced age at diagnosis. In addition, hedgehog and G2M checkpoint signatures were associated with younger age at metastatic presentation, whereas the PI3K signature was more pronounced in older patients. A more detailed analysis of 503 matched cases, revealed that mutations in CARD11, MYH11, ARID1A, KAT6B, KDM6A, KMT2A, ERBB4, GNAS, PTEN, BRCA2, and EPHB6 were enriched in patients with an older age at diagnosis, while acquired PTCH1 and ERCC4 mutations were more frequent in younger patients.

In conclusion, advanced breast cancer in older patients is characterized by distinct molecular features.