Article | Published:

Epidemiology

Metabolite and lipoprotein responses and prediction of weight gain during breast cancer treatment

British Journal of Cancervolume 119pages11441154 (2018) | Download Citation

Abstract

Background

Breast cancer treatment has metabolic side effects, potentially affecting risk of cardiovascular disease (CVD) and recurrence. We aimed to compare alterations in serum metabolites and lipoproteins during treatment between recipients and non-recipients of chemotherapy, and describe metabolite profiles associated with treatment-related weight gain.

Methods

This pilot study includes 60 stage I/II breast cancer patients who underwent surgery and were treated according to national guidelines. Serum sampled pre-surgery and after 6 and 12 months was analysed by MR spectroscopy and mass spectrometry. In all, 170 metabolites and 105 lipoprotein subfractions were quantified.

Results

The metabolite and lipoprotein profiles of chemotherapy recipients and non-recipients changed significantly 6 months after surgery (p < 0.001). Kynurenine, the lipid signal at 1.55–1.60 ppm, ADMA, 2 phosphatidylcholines (PC aa C38:3, PC ae C42:1), alpha-aminoadipic acid, hexoses and sphingolipids were increased in chemotherapy recipients after 6 months. VLDL and small dense LDL increased after 6 months, while HDL decreased, with triglyceride enrichment in HDL and LDL. At baseline, weight gainers had less acylcarnitines, phosphatidylcholines, lyso-phosphatidylcholines and sphingolipids, and showed an inflammatory lipid profile.

Conclusion

Chemotherapy recipients exhibit metabolic changes associated with inflammation, altered immune response and increased risk of CVD. Altered lipid metabolism may predispose for treatment-related weight gain.

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Note: This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License.

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Acknowledgements

We acknowledge each woman who participated in this clinical study, and our nurses Ragnhild Tveit, Alexandra Ødegaard and Harriet Børset.

Author information

Affiliations

  1. Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU–Norwegian University of Science and Technology, P.O. Box 8905 MTFS, Trondheim, 7491, Norway

    • Torfinn S. Madssen
    • , Tone F. Bathen
    •  & Guro F. Giskeødegård
  2. Department of Oncology, Oslo University Hospital, Oslo, 0424, Norway

    • Inger Thune
    • , Vidar G. Flote
    • , Hanne Frydenberg
    •  & Erik Wist
  3. Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, 9037, Norway

    • Inger Thune
  4. Department of Oncology, St. Olavs University Hospital, P.O. Box 3250 Sluppen, Trondheim, 7006, Norway

    • Steinar Lundgren
  5. Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU–Norwegian University of Science and Technology, P.O. Box 8905 MTFS, Trondheim, 7491, Norway

    • Steinar Lundgren
    •  & Hans E. Fjøsne
  6. Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU–Norwegian University of Science and Technology, Trondheim, 7491, Norway

    • Gro F. Bertheussen
  7. Department of Physical Medicine and Rehabilitation, St. Olav University Hospital of Trondheim, P.O. Box 3250 Sluppen, Trondheim, 7006, Norway

    • Gro F. Bertheussen
  8. Department of Breast and Endocrine Surgery, Oslo University Hospital, P.O. Box 4953 Nydalen, Oslo, 0424, Norway

    • Ellen Schlichting
  9. Bruker BioSpin GmbH, Application Method Development Group, Silberstreifen, 76287, Rheinstetten, Germany

    • Hartmut Schäfer
  10. Department of Surgery, St. Olavs University Hospital, P.O. Box 3250 Sluppen, Trondheim, 7006, Norway

    • Hans E. Fjøsne
  11. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, P.O Box 1171 Blindern, Oslo, 0318, Norway

    • Riyas Vettukattil
  12. Division of Paediatric and Adolescent Medicine, Oslo University Hospital, P.O. Box 4956 Nydalen, 0424, Oslo, Norway

    • Riyas Vettukattil
  13. Department of Pathology, Oslo University Hospital, P.O. Box 4953 Nydalen, Oslo, 0424, Norway

    • Jon Lømo

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Contributions

Study concept and design: T.S.M., I.T., V.G.F., S.L., G.F.B., H.F., E.W., E.S., H.E.F., J.L., T.F.B. and G.F.G. Data collection and acquisition: I.T., V.G.F., S.L., G.F.B., H.F., H.S., H.E.F., R.V., T.F.B. and G.F.G. Data analysis and interpretation: T.S.M., I.T., T.F.B. and G.F.G. Manuscript writing: T.S.M., T.F.B. and G.F.G. Manuscript editing: all authors. All authors read and approved the final version of the paper.

Ethics approval and consent to participate:

The study was approved by The Regional Committee for Medical and Health Research Ethics South East (REK 2011/500), and all patients gave informed written consent to participate. The study was performed in accordance with the Declaration of Helsinki.

Funding:

This work was supported by grants from the South–East Norwegian Health Authority (Grant 2012064), Norwegian Research Council (Grant 213997), Active Against Cancer-Gjensidige Siftelsen (Grant 2012) and the Norwegian Cancer Society (Grant 163243).

Data availability:

The metabolomics data can be made available from the authors upon request.

Competing interests

The authors declare no competing interests.

Note:

This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Corresponding author

Correspondence to Guro F. Giskeødegård.

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https://doi.org/10.1038/s41416-018-0211-x