BJMO - volume 16, issue 1, february 2022
T. Geukens MD, M. De Schepper MD, F. Richard PhD, M. Maetens PhD, K. Van Baelen MD, S. Leduc MSc, E. Isnaldi MD, PhD, H.L. Nguyen MSc, I. Bachir MD, E. Vanden Berghe MSc, W. Van Den Bogaert MD, K. Punie MD, P. Neven MD, PhD, H. Wildiers MD, PhD, G. Floris MD, PhD, C. Desmedt PhD
The purpose of this review is to highlight the recent knowledge gathered on the genomics of metastatic breast cancer (BC), together with the clinical implications. Through large sequencing efforts, the genomic profile of BC is increasingly being deciphered, with a limited number of those findings having resulted in genomicmatched treatment options. The pace at which new discoveries are made is highest in the early setting, where large samples can easily be accessed through leftover tissue of resection specimens, and smaller diagnostic biopsies are also available. In the metastatic setting however, residual tissue from clinically indicated biopsies or resections are scarce. Some efforts have been undertaken through (inter)national, institutional, clinical trial- or patient-driven initiatives. They have highlighted important differences between the genomic landscape of metastatic versus primary tumour tissues. Especially in hormone receptor positive HER2 negative (HR+/HER2-) disease, driver mutations continue to accumulate after dissemination, most of them in the ESR1 or ERBB2 genes, or in genes involved in transcription regulation, MAPK- or PI3K-signaling pathways. Importantly, the genomic landscape is not homogeneous even within one patient, and significant heterogeneity is seen on an intra-patient, inter-lesion and intra-lesion level. This poses clinical challenges, with different subclones possibly harbouring differential sensitivity to systemic treatments and single biopsies not accurately reflecting the full molecular profile. Finally, through liquid biopsies, a more complete and less invasive insight into the tumour’s characteristic could theoretically be retrieved. However, it is unclear how well these profiles correlate with the actual diversity of the different lesions. Importantly, rapid autopsy programs have been shown to enhance research on the genomics of metastatic BC, and one such program was recently launched at UZ/KU Leuven.
(BELG J MED ONCOL 2022;16(1):18–28)
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