CDKi have significantly improved PFS and OS in MBC HR+/HER2- patients. However, their benefit is not observed in all treated patients and currently no predictive marker has been identified. Dysregulated lipid metabolism, including alterations in fatty acid (FA) transport, uptake, and oxidation has been associated with BC outcome. The lipidome is a very sensitive measure of the lipidic phenotype and reflect its alteration. The purpose of this study is to identify lipidomic signatures with prognostic and predictive ability in patients with ER+ MBC candidate do ET + CDK 4/6i.
Thirty consecutive MBC ER+/HER2- patients were prospectively enrolled in this study. Plasma samples were collected at baseline. The lipidomic analysis was conducted following an untargeted approach, based on 1139 lipids. Analyses were performed by combining liquid chromatography and mass spectrometry. The lipidomic profile of 23 patients who achieved a PR or SD at 6 months was compared with the 7 patients who experienced disease progression or death. Moreover, a comparison was performed between patients with visceral disease (n=8) and those with bone/soft tissue disease (n=22). The differentially expressed lipids were computed by calculating the Fold Change with a p-value <0.05.
We identified 53 lipids differentially expressed: 9 were overexpressed in responding patients and 44 in those with PD/death. In the second analysis 41 differentially expressed lipids were identified according to metastatic site. By multivariate analysis 8 hypothetical biomarkers were identified in the first comparison and 6 in the second group: in responding patients higher baseline concentrations of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin and ceramides were detected, whereas those with higher levels of triacylglycerols (TG) and carnitine were more likely to have resistant disease. TG, diacylglycerols (DG) and cholesterol higher levels were found in patients with visceral compared to patients with bone/soft tissue disease.
These preliminary results suggest that lipidomic profiling might be further exploited as a possible tool to discover predictive biomarkers of response to CDKi.
The authors.
AIRC - Associazione Italiana Ricerca sul Cancro.
A. Gennari: Other, Personal, Other: Roche. All other authors have declared no conflicts of interest.