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Published in: Molecular Imaging and Biology 5/2019

Open Access 01-10-2019 | Breast Cancer | Research Article

PIK3CA Mutational Status Is Associated with High Glycolytic Activity in ER+/HER2− Early Invasive Breast Cancer: a Molecular Imaging Study Using [18F]FDG PET/CT

Authors: Heinrich Magometschnigg, Katja Pinker, Thomas Helbich, Anita Brandstetter, Margaretha Rudas, Thomas Nakuz, Pascal Baltzer, Wolfgang Wadsak, Marcus Hacker, Michael Weber, Peter Dubsky, Martin Filipits

Published in: Molecular Imaging and Biology | Issue 5/2019

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Abstract

Purpose

In PIK3CA mutant breast cancer, downstream hyperactivation of the PI3K/AKT/mTOR pathway may be associated with increased glycolysis of cancer cells. The purpose of this study was to investigate the functional association of PIK3CA mutational status and tumor glycolysis in invasive ER+/HER2− early breast cancer.

Procedures

This institutional review board-approved retrospective study included a dataset of 67 ER+/HER2− early breast cancer patients. All patients underwent 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/X-ray computed tomography ([18F]FDG PET/CT) and clinico-pathologic assessments as part of a prospective study. For this retrospective analysis, pyrosequencing was used to detect PIK3CA mutations of exons 4, 7, 9, and 20. Tumor glucose metabolism was assessed semi-quantitatively with [18F]FDG PET/CT using maximum standardized uptake values (SUVmax). SUVmax values were corrected for the partial volume effect, and metabolic tumor volume was calculated using the volume of interest automated lesion growing function 2D tumor size, i.e., maximum tumor diameter was assessed on concurrent pre-treatment contrast-enhanced magnetic resonance imaging.

Results

PIK3CA mutations were present in 45 % of all tumors. Mutations were associated with a small tumor diameter (p < 0.01) and with low nuclear grade (p = 0.04). Glycolytic activity was positively associated with nuclear grade (p = 0.01), proliferation (p = 0.002), regional lymph node metastasis (p = 0.015), and metabolic tumor volume (p = 0.001) but not with tumor size/T-stage. In invasive ductal carcinomas, median SUVmax was increased in PIK3CA-mutated compared to wild-type tumors; however, this increase did not reach statistical significance (p = 0.05). Multivariate analysis of invasive ductal carcinomas revealed [18F]FDG uptake to be independently associated with PIK3CA status (p = 0.002) and nuclear tumor grade (p = 0.046). Size, volume, and regional nodal status had no influence on glycolytic activity. PIK3CA mutational status did not influence glycolytic metabolism in lobular carcinomas. Glycolytic activity and PIK3CA mutational status had no significant influence on recurrence-free survival or disease-specific survival.

Conclusions

In ER+/HER2− invasive ductal carcinomas of the breast, glucose uptake is independently associated with PIK3CA mutations. Initial data suggest that [18F]FDG uptake reflects complex genomic alterations and may have the potential to be used as candidate biomarker for monitoring therapeutic response and resistance mechanisms in emerging therapies that target the PI3K/AKT/mTOR pathway.
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Metadata
Title
PIK3CA Mutational Status Is Associated with High Glycolytic Activity in ER+/HER2− Early Invasive Breast Cancer: a Molecular Imaging Study Using [18F]FDG PET/CT
Authors
Heinrich Magometschnigg
Katja Pinker
Thomas Helbich
Anita Brandstetter
Margaretha Rudas
Thomas Nakuz
Pascal Baltzer
Wolfgang Wadsak
Marcus Hacker
Michael Weber
Peter Dubsky
Martin Filipits
Publication date
01-10-2019
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 5/2019
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-018-01308-z

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