Newcastle Magnetic Resonance Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Int J Mol Sci. 2024 Aug 28;25(17):9303. doi: 10.3390/ijms25179303.
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.
从从头合成和缺氧中释放出的单不饱和脂肪酸、多不饱和脂肪酸和饱和脂肪酸(MUFAs、PUFAs、SFAs)的失调是乳腺癌的核心代谢特征。新辅助化疗(NACT)的早期反应标志物对于乳腺癌患者的分层治疗至关重要,而脂质代谢和正常氧合的恢复可能先于可观察到的结构变化。在这项研究中,我们假设在接受 NACT 的乳腺癌患者中,肿瘤周围的脂质组成和缺氧可能是预测和早期反应的标志物。女性乳腺癌患者在基线和第 1 周期在 3T 临床 MRI 扫描仪上进行扫描,采集 MUFAs、PUFAs 和 SFAs 的脂质组成图以及有效横向弛豫率 R2的缺氧图。用基线参考计算第 1 周期脂质组成和缺氧的百分比变化。根据活检和切除的 CD163 免疫染色分析肿瘤相关巨噬细胞,计算整个 NACT 过程中切除肿瘤的百分比变化。我们发现基线和第 1 周期时,良好反应者和不良反应者之间的脂质组成和 R2 没有显著差异;然而,MUFAs 和 PUFAs 的百分比变化与 CD163 之间的相关性表明,脂质的改变与免疫反应可能支持靶向治疗的发展。