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Circulating adipose stromal cells as a response biomarker in phase II energy balance trials of obese breast cancer survivors and high-risk women

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Abstract

Purpose

Circulating adipose stromal cells (CASC) are thought to be increased in obesity and facilitate angiogenesis, and tumor metastases.

Methods

CASC were identified from buffy coat peripheral blood mononuclear cells (PBMCs) by flow cytometry as CD34brightCD31 CD45 and CASC frequency was compared to adiposity measures in 33 women at increased risk for breast cancer. Feasibility of CASC as a response biomarker for a diet and exercise intervention in ten breast cancer survivors was then explored.

Results

For 33 high-risk women, median CASC frequency was 9.7 per million PBMCs and trended positively with body mass index, fat mass index (FMI), and percent android fat. Correlation was significant when BMI was dichotomized at > versus < 35 kg/m2 (p = 0.02). For ten breast cancer survivors with a median BMI of 37 kg/m2, median CASC frequency was 16.4 per million PBMCs. In univariate analyses, change in BMI, total fat and visceral fat were significantly correlated with change in CASC frequency. On multivariate analysis, change in visceral adipose had the strongest association with change in CASC frequency (p < 0.00078).

Conclusions

The association between the reduction in visceral adipose tissue and the decrease in frequency of circulating adipose stromal cells suggests that the latter might be a useful biomarker in clinical trials of obese breast cancer survivors undergoing a weight loss intervention.

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Acknowledgements

This work was supported in part by grants from the Breast Cancer Research Foundation. We acknowledge the Flow Cytometry Core Laboratory, which is sponsored, in part, by the NIH/NIGMS COBRE Grant P30 GM103326.

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Correspondence to Carol J. Fabian.

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The authors declare that they have no conflict of interest.

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The conduct of the trial complies with the current laws of the United States of America.

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All procedures and protocols were approved by the Human Subjects Committee (Institutional Review Board) of the University of Kansas Medical Center. All studies have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

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Written informed consent was obtained from all participants.

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Baker, H.A., Fabian, C.J., Hastings, R.C. et al. Circulating adipose stromal cells as a response biomarker in phase II energy balance trials of obese breast cancer survivors and high-risk women. Breast Cancer Res Treat 176, 387–394 (2019). https://doi.org/10.1007/s10549-019-05251-7

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  • DOI: https://doi.org/10.1007/s10549-019-05251-7

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