Breast cancer is the leading cause of cancer-related deaths amongst women worldwide. One of the critical challenges in treating this disease is the presence of mutations in the PIK3CA gene, an oncogene that plays a significant role in breast cancers that are unresponsive to conventional chemotherapy and hormone treatments. Metastatic breast cancer, characterised by the spread of cancer cells from the breast to other organs, currently lacks curative options. As the disease progresses, the genetic profile of metastatic tumours may differ from the primary tumour, making it essential to find effective ways to monitor and target these mutations.
The suggested read for this month provides insight on how circulating tumour cells (CTCs) may offer a promising approach to this challenge. These cells, shed by tumours into the bloodstream, can serve as a “real-time biopsy,” providing a more accurate representation of the tumour’s current genetic makeup compared to traditional biopsies of the primary tumour. The study aimed to highlight this characteristic by performing “liquid biopsies” using CTCs to identify mutations in breast cancer patients.
In the study, blood samples were collected from twenty patients with metastatic breast cancer (MBC). If a high number of CTCs were detected in the blood, these cells were isolated and sequenced, focusing on exons 9 and 20 of the PIK3CAgene. Two distinct mutations were identified in exon 9: Q546K and E545G. These findings prompted further investigation into the genetic landscape of patients harbouring these mutations.
A 26-gene panel was used to detect additional genetic variants linked to PIK3CA mutations. This analysis revealed that mutations in the TP53 gene were frequently associated with PIK3CA mutations. Interestingly, these TP53 mutations were not present in metastatic tissues, suggesting they are specific to the primary tumour. Therefore, the CTCs enabled the identification of the genetic profile of the breast tumour using a less invasive process.
In addition to CTC analysis, cell-free tumoral DNA can also be valuable tool for sequencing and provides insights into the genetic profile of the primary tumour. However, its low concentration in the bloodstream makes it challenging to detect. Therefore, the study suggests the potential advantage of CTCs, which are known for their ability to form metastases, and chose molecular characterisation might serve as a crucial prognostic tool. CTCs can be used to search for tumour-specific mutations, highlighting the importance of analysing multiple cells, including those with atypical phenotypes and immunophenotypes, to fully understand the tumour’s genetic diversity.
We at 4bases introduce the Pancancer Pro oncological kit, powered by NGS technologies, which allows for somatic analysis of solid and haematological tumours for precision medicine and cancer therapy selection. It allows for the analysis of ninety-five genes related to several solid tumours, using DNA extracted blood or body tissue samples. Learn more about the product here: https://4bases.ch/oncological-kits/
Elena Marino, Cristian Mauro, Elena Belloni, Marco Picozzi, Valentina Favalli, Maria Cristina Cassatella, Laura Zorzino, Luciano Giacò, Pier Giuseppe Pelicci, Massimo Barberis, Maria Teresa Sandri, Loris Bernard, PIK3CA mutation analysis in circulating tumor cells of patients with hormone receptor positive metastatic breast cancer, Biochemistry and Biophysics Reports, Volume 39, 2024, 101805, ISSN 2405-5808, https://doi.org/10.1016/j.bbrep.2024.101805.
