Serum fatty acid profiles across clinicopathologic heterogeneity in breast cancer: an exploratory study

Breast cancer (BC) is the most frequently diagnosed malignancy and the leading cause of cancer-related death in women. Beyond traditional clinical classifications, metabolic reprogramming has emerged as an additional layer of tumor heterogeneity. Fatty acids (FAs), essential for membrane synthesis, energy storage, and signaling, undergo dynamic remodeling in cancer and may reflect disease progression.

To examine associations between serum FAs profiles and clinical-pathological features of BC, including tumor stage, surrogate subtype, lymph node status, and proliferative activity.

A retrospective, cross-sectional study was conducted at a single institution to analyze metabolic signatures in patients with BC stratified by clinical and surrogate characteristics.

Serum FAs composition was analyzed by gas chromatography-mass spectrometry in 110 patients with BC before treatment initiation. Patients were categorized according to tumor stage, BC surrogate subtype, and Ki-67 proliferation index. Group comparisons and correlations were performed using standard parametric/non-parametric tests as appropriate, with Benjamini-Hochberg false discovery rate (FDR) correction across the FAs panel.

In categorical comparisons (e.g., tumor stage, Ki-67, lymph node status), some FAs, particularly arachidonic acid (ARA), and selected saturated, branched-chain, and polyunsaturated species, were nominally elevated in more aggressive phenotypes, but none remained significant after FDR correction (Q = 0.05). Correlation analysis using Ki-67 as a continuous variable revealed modest but consistent positive associations with multiple FAs. Notably, ARA, dihomo-γ-linolenic acid, docosapentaenoic acid, and several branched- and odd-chain species remained significantly correlated with Ki-67 after FDR adjustment.

This exploratory study suggests that specific serum FAs are modestly associated with tumor proliferative activity, supporting the concept that aggressive BC phenotypes may involve systemic lipid remodeling. Further prospective studies are needed to validate these findings and assess their potential clinical relevance.