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Updated: Jun 16, 2026
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer
Ruth E Board1, Andrew M Wardley, J Michael Dixon
1Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, M20 4BX, UK.
Abstract:
Somatic mutations in PIK3CA (encoding a class I phosphoinositide 3 kinase (PI3K) subunit) modulate PI3K signalling to influence tumour behaviour and occur in up to 40% of breast cancers. Inhibitors of PI3K signalling are entering clinical trials, but the impact of PIKC3A mutation on tumour response has yet to be clarified. This study investigated the potential utility of circulating free DNA (cfDNA) as a source for PIK3CA mutation detection in patients with breast cancer. cfDNA extracted (QIAamp Virus spin kit) from blood and matched archival tumour from 46 patients with metastatic breast cancer and 30 patients with localised, operable breast cancer was assessed for hotspot PIK3CA mutations using Amplification Refractory Mutation System (ARMS()) allele-specific PCR and Scorpion probes. PIK3CA mutations were detected in 13/46 (28%) plasma-derived and 10/46 (21%) serum-derived cfDNA samples from metastatic breast cancer patients. In 41 cases with matched tumour and plasma-derived cfDNA data, concordance (same mutation status in plasma and tumour) was 95%. Where a PIK3CA mutation was present in tumour, the 'pick up' in plasma-derived cfDNA was 80%. PIK3CA mutations were present in tumours from 14/30 (47%) localised breast cancers, but no PIK3CA mutations were detected in matched cfDNA. These data demonstrate feasibility and potential utility of cfDNA for PIK3CA mutation detection in patients with metastatic breast cancer. Studies are underway to qualify PIK3CA mutation in cfDNA as a predictive biomarker allowing patient stratification in clinical trials of mechanism-based therapeutics that target PI3K signalling pathways.
Insights
Detecting PIK3CA mutations in circulating tumor DNA (ctDNA) is feasible in metastatic breast cancer patients. This blood-based test shows high concordance with tumor mutations, aiding clinical trial stratification.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Somatic mutations in PIK3CA are common in breast cancer, influencing tumor behavior.
- PI3K pathway inhibitors are in clinical trials, but PIK3CA mutation's impact on response needs clarification.
- Circulating free DNA (cfDNA) offers a potential non-invasive source for PIK3CA mutation detection.
Purpose of the Study:
- To investigate the utility of cfDNA for detecting PIK3CA mutations in breast cancer patients.
- To assess the concordance between cfDNA and tumor-derived PIK3CA mutation status.
- To evaluate cfDNA as a potential biomarker for patient stratification in clinical trials.
Main Methods:
- cfDNA was extracted from plasma and serum of 46 metastatic and 30 localized breast cancer patients.
- Matched archival tumor tissue was also analyzed.
- Hotspot PIK3CA mutations were detected using Amplification Refractory Mutation System (ARMS) allele-specific PCR and Scorpion probes.
Main Results:
- PIK3CA mutations were detected in 28% of plasma cfDNA and 21% of serum cfDNA from metastatic patients.
- Concordance between plasma cfDNA and tumor PIK3CA mutation status was 95% in 41 matched cases.
- Tumor PIK3CA mutations were detected in 80% of plasma cfDNA when present in the tumor.
- No PIK3CA mutations were found in cfDNA from localized breast cancer patients, despite 47% having tumor mutations.
Conclusions:
- cfDNA is a feasible and potentially useful source for PIK3CA mutation detection in metastatic breast cancer.
- PIK3CA mutation detection in cfDNA could serve as a predictive biomarker for patient stratification in clinical trials targeting PI3K signaling.
- Further studies are needed to fully qualify cfDNA-based PIK3CA mutation analysis as a clinical biomarker.
