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Open Access 01-12-2018 | Research article

Intracellular hypoxia measured by ¹⁸F-fluoromisonidazole positron emission tomography has prognostic impact in patients with estrogen receptor-positive breast cancer

Authors: Aya Asano, Shigeto Ueda, Ichiei Kuji, Tomohiko Yamane, Hideki Takeuchi, Eiko Hirokawa, Ikuko Sugitani, Hiroko Shimada, Takahiro Hasebe, Akihiko Osaki, Toshiaki Saeki

Published in: Breast Cancer Research | Issue 1/2018

Abstract

Background

Hypoxia is a key driver of cancer progression. We evaluated the prognostic impact of ¹⁸F-fluoromisonidazole (FMISO) prior to treatment in patients with breast cancer.

Methods

Forty-four patients with stage II/III primary breast cancer underwent positron emission tomography/computed with ¹⁸F-fluorodeoxyglucose (FDG-PET/CT) and FMISO. After measurement by FDG-PET/CT, the tissue-to-blood ratio (TBR) was obtained using FMISO-PET/CT. FMISO-TBR was compared for correlation with clinicopathological factors, disease-free survival (DFS), and overall survival (OS). Multiplex cytokines were analyzed for the correlation of FMISO-TBR.

Results

Tumors with higher nuclear grade and negativities of estrogen receptor (ER) and progesterone receptor had significantly higher FMISO-TBR than other tumors. Kaplan-Meier survival curves showed that patients with a higher FMISO-TBR (cutoff, 1.48) had a poorer prognosis of DFS (p = 0.0007) and OS (p = 0.04) than those with a lower FMISO-TBR. Multivariate analysis indicated that higher FMISO-TBR and ER negativity were independent predictors of shorter DFS (p = 0.01 and 0.03). Higher FMISO-TBR was associated with higher plasma levels of angiogenic hypoxic markers such as vascular endothelial growth factor, transforming growth factor-α, and interleukin 8.

Conclusions

FMISO-PET/CT is useful for assessing the prognosis of patients with breast cancer, but it should be stratified by ER status.

Trial registration

UMIN Clinical Trials Registry, UMIN000006802. Registered on 1 December 2011.

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Title: Intracellular hypoxia measured by 18F-fluoromisonidazole positron emission tomography has prognostic impact in patients with estrogen receptor-positive breast cancer
Authors: Aya Asano
Shigeto Ueda
Ichiei Kuji
Tomohiko Yamane
Hideki Takeuchi
Eiko Hirokawa
Ikuko Sugitani
Hiroko Shimada
Takahiro Hasebe
Akihiko Osaki
Toshiaki Saeki
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue 1/2018
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-018-0970-6

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