TY - JOUR
T1 - Peri-Tumoural Lipid Composition and Hypoxia for Early Immune Response to Neoadjuvant Chemotherapy in Breast Cancer
AU - Cheung, Sai Man
AU - Chan, Kwok-Shing
AU - Senn, Nicholas
AU - Husain, Ehab
AU - Sharma, Ravi
AU - McGoldrick, Trevor
AU - Gagliardi, Tanja
AU - Masannat, Yazan
AU - He, Jiabao
N1 - The authors would like to thank Matthew Clemence (Philips Healthcare Clinical Science, UK) for clinical scientist 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.
PY - 2024/8/28
Y1 - 2024/8/28
N2 - 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.
AB - 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.
U2 - 10.3390/ijms25179303
DO - 10.3390/ijms25179303
M3 - Article
C2 - 39273252
SN - 1422-0067
VL - 25
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 17
M1 - 9303
ER -