Peri-Tumoural Lipid Composition and Hypoxia for Early Immune Response to Neoadjuvant Chemotherapy in Breast Cancer

Sai Man Cheung; Kwok-Shing Chan; Nicholas Senn; Ehab Husain; Ravi Sharma; Trevor McGoldrick; Tanja Gagliardi; Yazan Masannat; Jiabao He

doi:10.3390/ijms25179303

Peri-Tumoural Lipid Composition and Hypoxia for Early Immune Response to Neoadjuvant Chemotherapy in Breast Cancer

Sai Man Cheung^* (Corresponding Author)
, Kwok-Shing Chan
, Nicholas Senn
, Ehab Husain
, Ravi Sharma
, Trevor McGoldrick
, Tanja Gagliardi
, Yazan Masannat
, Jiabao He

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

The deregulation of monounsaturated, polyunsaturated, and saturated fatty acids (MUFAs, PUFAs, SFAs) from de novo synthesis and hypoxia are central metabolic features of breast tumour. Early response markers for neoadjuvant chemotherapy (NACT) are critical for stratified treatment for patients with breast cancer, and restoration of lipid metabolism and normoxia might precede observable structural change. In this study, we hypothesised that peri-tumoural lipid composition and hypoxia might be predictive and early response markers in patients with breast cancer undergoing NACT. Female patients with breast cancer were scanned on a 3T clinical MRI scanner at baseline and Cycle1, with acquisition of lipid composition maps of MUFAs, PUFAs, and SFAs, and hypoxia maps of effective transverse relaxation rate R2*. The percentage change in lipid composition and hypoxia at Cycle1 was calculated with reference to baseline. Tumour-associated macrophages were analysed based on immunostaining of CD163 from biopsy and resection, with the percentage change in the resected tumour calculated across the entire NACT. We found no significant difference in lipid composition and R2* between good and poor responders at baseline and Cycle1; however, the correlation between the percentage change in MUFAs and PUFAs against CD163 suggested the modulation in lipids with altered immune response might support the development of targeted therapies.

Original language	English
Article number	9303
Number of pages	15
Journal	International Journal of Molecular Sciences
Volume	25
Issue number	17
DOIs	https://doi.org/10.3390/ijms25179303
Publication status	Published - 28 Aug 2024

Bibliographical note

The authors would like to thank Matthew Clemence (Philips Healthcare Clinical Science, UK) for support; Erica Banks and Alison McKay for patient recruitment support; Teresa Morris and Dawn Younie for logistics support; Beverly McLennan, Nichola Crouch, Laura Reid, Mike Hendry for radiographer support; and Gordon Urquhart for providing access to the patients.

Data Availability Statement

The raw data supporting the conclusions of this article will be made available by the authors on request.

Funding

The study was jointly funded by the National Health Service Grampian Endowment Research Fund (16/11/047); Friends of Aberdeen and North Centre for Haematology, Oncology and Radiotherapy (RS17 004); and Tenovus Scotland (G16.09). N.S.’s PhD study was supported by the Biotechnology and Biological Sciences Research Council (1654748, BB/M010996/1). S.M.C. was funded by Cancer Research UK (C68628/A28312).

Funders	Funder number
National Health Service	16/11/047
Biotechnology and Biological Sciences Research Council	BB/M010996/1
Cancer Research UK	C68628/A28312

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Cite this

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abstract = "The deregulation of monounsaturated, polyunsaturated, and saturated fatty acids (MUFAs, PUFAs, SFAs) from de novo synthesis and hypoxia are central metabolic features of breast tumour. Early response markers for neoadjuvant chemotherapy (NACT) are critical for stratified treatment for patients with breast cancer, and restoration of lipid metabolism and normoxia might precede observable structural change. In this study, we hypothesised that peri-tumoural lipid composition and hypoxia might be predictive and early response markers in patients with breast cancer undergoing NACT. Female patients with breast cancer were scanned on a 3T clinical MRI scanner at baseline and Cycle1, with acquisition of lipid composition maps of MUFAs, PUFAs, and SFAs, and hypoxia maps of effective transverse relaxation rate R2*. The percentage change in lipid composition and hypoxia at Cycle1 was calculated with reference to baseline. Tumour-associated macrophages were analysed based on immunostaining of CD163 from biopsy and resection, with the percentage change in the resected tumour calculated across the entire NACT. We found no significant difference in lipid composition and R2* between good and poor responders at baseline and Cycle1; however, the correlation between the percentage change in MUFAs and PUFAs against CD163 suggested the modulation in lipids with altered immune response might support the development of targeted therapies. ",

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AU - McGoldrick, Trevor

AU - Gagliardi, Tanja

AU - Masannat, Yazan

AU - He, Jiabao

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Peri-Tumoural Lipid Composition and Hypoxia for Early Immune Response to Neoadjuvant Chemotherapy in Breast Cancer

Abstract

Bibliographical note

Data Availability Statement

Funding

UN SDGs

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