PIK3CA mutational status in circulating tumor cells can change during disease recurrence or progression in patients with breast cancer.

Abstract

PURPOSE:

Molecular characterization of circulating tumor cells (CTC) is crucial for the investigation of molecular-targeted therapies while PIK3CA somatic mutations play a crucial role in therapy response. We investigated the presence of PIK3CA mutations in CTC and whether this is associated with clinical outcome.

EXPERIMENTAL DESIGN:

We developed and validated an ultrasensitive methodology for the detection of PIK3CA mutations that is based on a combination of allele-specific, asymmetric rapid PCR and melting analysis. We analyzed PIK3CA hotspot mutations in: (i) a training group consisting of EpCAM-positive CTC fraction from 37 patients with clinically confirmed metastasis, and 26 healthy female volunteers and 15 primary breast tumor tissues and (ii) an independent group consisting of EpCAM-positive CTC fraction from 57 metastatic and 118 operable breast cancer patients and 76 corresponding primary tumors.

RESULTS:

The assay could detect 0.05% of mutated dsDNA in the presence of 99.95% wtDNA for both exons (9 and 20) and was highly specific (0/26 healthy donors). PIK3CA mutations were identified in EpCAM-positive CTC in 20 of 57(35.1%) and in 23 of 118 (19.5%) patients with metastatic and operable breast cancer, and in 45 of 76(59.2%) corresponding FFPEs. Our data indicate that PIK3CA mutational status in CTCs can change during disease progression and is associated with worse survival (P = 0.047).

CONCLUSIONS:

PIK3CA hotspot mutations are present at a relatively high frequency in CTCs and their presence is associated with worse survival in patients with breast cancer with metastasis. Evaluation of PIK3CA mutational status in CTCs is a strategy with potential clinical application.

• Authors: Athina Markou, Sofia Farkona, Christina Schiza, Tonia Efstathiou, Sophia Kounelis, Nikos Malamos, Vassilis Georgoulias, Evi Lianidou
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 20 Issue 22 Pg. 5823-34 (Nov 15 2014) ISSN: 1557-3265 [Electronic] United States
• PMID: 25398847 (Publication Type: Journal Article)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• Phosphatidylinositol 3-Kinases
• Class I Phosphatidylinositol 3-Kinases
• PIK3CA protein, human

Topics

• Breast Neoplasms (diagnosis, genetics, mortality, pathology)
• Case-Control Studies
• Cell Line, Tumor
• Class I Phosphatidylinositol 3-Kinases
• DNA Mutational Analysis (methods)
• Disease Progression
• Exons
• Female
• Humans
• Mutation
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Neoplastic Cells, Circulating (metabolism)
• Phosphatidylinositol 3-Kinases (genetics)
• Prognosis
• Sensitivity and Specificity