Abstract 303P
Background
The phosphatidylinositol-3-kinase (PI3K) signaling pathway plays an important role in tumorigenesis. One of the most common somatic mutations of PI3K in the p110a subunit (PIK3CA) occurs in various types of solid tumors. The presence of PIK3CA is associated with shorter survival and resistance to chemotherapy and radiation therapy.
Methods
We examined liquid biopsies from 32 breast cancer patients (17 in adjuvant and 15 in metastatic stage) with digital droplet PCR (ddPCR). This is a PCR technology that allows for accurate absolute quantification of target molecules with a very high degree of sensitivity. In essence, the method combines the simplicity of traditional PCR and the functions of quantitative real-time PCR (qRT-PCR). Unlike qRT-PCR, quantification is absolute and no standard calibration is used, which makes the process faster, more accurate and reproducible. The basic principle involves extreme dilution and separation of the sample into millions of individual units / droplets, which ideally contain or do not contain the desired molecule.
Results
The reported incidence of PIK3CA for breast cancer varies between 8% and 40%. Over 90% of the mutations were found in exons 7, 9 and 20. Somatic mutations in PIK3CA were found in 15.6 % of our patients. Of these, 80 % were in patients with metastatic disease. The results obtained from us correspond to the reported statistics from other clinical trials. PIK3CA mutations are extremely heterogeneous. This initial data can be the basis for validating a panel for ‘hotspot‘ mutations for monitoring. The identification of oncogenic PIK3CA mutations from plasma-derived ctDNA by ddPCR can be used as a reliable, non-invasive assay to assess the effect of treatment with target molecules and as a prognostic factor for expected survival.
Conclusions
Digital genomic technologies offer higher sensitivity than massive parallel sequencing technologies and can be used as a method to validate results and quantify ctDNA. Cost-effective and faster methods are those in which a ctDNA plasma sample can be used for non-invasive monitoring. The PIK3CA mutations thus discovered can be used as a predictive factor for treatment with PI3K inhibitors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.