(1)H-NMR Plasma Lipoproteins Profile Analysis Reveals Lipid Metabolism Alterations in HER2-Positive Breast Cancer Patients

SIMPLE SUMMARY: Lipids’ metabolism deregulation is an established mark of breast cancer, however, no conclusive results have been reported on its effective role in disease development and progression. In this study, we applied straightforward (1)H-NMR analysis to deeply explore alterations in circulating lipoproteins in HER2-positive breast cancer patients. The results support the key role played by lipids in the development of this breast cancer histotype and point out a specific lipid trait, characterized by a high plasma level of VLDL subfractions, potentially useful for diagnostic purposes. Moreover, the monitoring of plasma lipoproteins profile changes along the therapeutic interventions was found valuable to predict the clinical outcome. ABSTRACT: The lipid tumour demand may shape the host metabolism adapting the circulating lipids composition to its growth and progression needs. This study aims to exploit the straightforward (1)H-NMR lipoproteins analysis to investigate the alterations of the circulating lipoproteins’ fractions in HER2-positive breast cancer and their modulations induced by treatments. The baseline (1)H-NMR plasma lipoproteins profiles were measured in 43 HER2-positive breast cancer patients and compared with those of 28 healthy women. In a subset of 32 patients, longitudinal measurements were also performed along neoadjuvant chemotherapy, after surgery, adjuvant treatment, and during the two-year follow-up. Differences between groups were assessed by multivariate PLS-DA and by univariate analyses. The diagnostic power of lipoproteins subfractions was assessed by ROC curve, while lipoproteins time changes along interventions were investigated by ANOVA analysis. The PLS-DA model distinguished HER2-positive breast cancer patients from the control group with a sensitivity of 96.4% and specificity of 90.7%, mainly due to the differential levels of VLDLs subfractions that were significantly higher in the patients’ group. Neoadjuvant chemotherapy-induced a significant drop in the HDLs after the first three months of treatment and a specific decrease in the HDL-3 and HDL-4 subfractions were found significantly associated with the pathological complete response achievement. These results indicate that HER2-positive breast cancer is characterized by a significant host lipid mobilization that could be useful for diagnostic purposes. Moreover, the lipoproteins profiles alterations induced by the therapeutic interventions could predict the clinical outcome supporting the application of (1)H-NMR lipoproteins profiles analysis for longitudinal monitoring of HER2-positive breast cancer in large clinical studies.