Effects of DHA Oral Supplementation on Plasma Resolvin D1 and D2 Levels in Naïve Breast Cancer Patients

<b>Background/Objectives</b>: Specialized pro-resolving lipid mediators, such as resolvins derived from omega-3 fatty acids, play a key role in resolving inflammation and restoring homeostasis. Resolvin D1 and D2, derived from docosahexaenoic acid (DHA), have demonstrated inflammation pro-resolving properties and potential anticancer effects. This study aimed to evaluate the effects of oral DHA supplementation on plasma resolvin D1 and D2 levels in breast cancer patients and in controls, and by stratifying the patients by disease presentation (sporadic, familial, BRCA1/2 mutated) and immunohistochemical characteristics. <b>Methods</b>: This is a single-center, interventional, controlled study conducted in women with breast cancer and women with benign breast disease, serving as controls. Participants consumed DHA (2 g/day) as algal oil syrup for 10 consecutive days. Plasma resolvin D1 and D2 levels were measured at baseline (T0) and after supplementation (T1) using ELISA kits. <b>Results</b>: At baseline, breast cancer patients exhibited higher plasma resolvin D1 levels compared to controls (median 21.3 vs. 7.3 pg/mL, <i>p</i> = 0.039), with no significant difference in resolvin D2. Following DHA supplementation, resolvin D1 and D2 significantly increased in BRCA1/2-mutated patients (+185.8% and +101.2%, <i>p</i> = 0.037, <i>p</i> = 0.028, respectively). Conversely, the familial breast cancer group showed a significant decrease in resolvin D1 (<i>p</i> = 0.015). Patients with low Ki67 expression showed greater increase over time of resolvin D2 levels compared to those with high Ki67 expression (<i>p</i> = 0.046). <b>Conclusions</b>: DHA supplementation modulated resolvin levels in breast cancer patients, with significant increase in BRCA1/2-mutated patients, suggesting enhanced inflammation pro-resolving responses. The reduction in resolvin D1 in the familial group highlights a potential dysregulated response. These findings indicate the potential of resolvins as biomarkers of resolution of inflammation and novel therapeutic targets in breast cancer.