Background/Objectives: 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.Methods: 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.Results: At baseline, breast cancer patients exhibited higher plasma resolvin D1 levels compared to controls (median 21.3 vs. 7.3 pg/mL,p= 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%,p= 0.037,p= 0.028, respectively). Conversely, the familial breast cancer group showed a significant decrease in resolvin D1 (p= 0.015). Patients with low Ki67 expression showed greater increase over time of resolvin D2 levels compared to those with high Ki67 expression (p= 0.046).Conclusions: 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.
背景/目的：由ω-3脂肪酸衍生的消退素等促炎症消退脂质介质，在炎症消退和恢复稳态过程中发挥关键作用。源自二十二碳六烯酸（DHA）的消退素D1和D2已被证实具有促炎症消退特性及潜在抗癌效应。本研究旨在评估口服DHA补充剂对乳腺癌患者及对照组血浆消退素D1和D2水平的影响，并根据疾病表现（散发性、家族性、BRCA1/2突变型）及免疫组化特征对患者进行分层分析。 方法：本研究为单中心干预性对照研究，纳入乳腺癌患者及良性乳腺疾病女性作为对照组。受试者连续10天服用藻油糖浆形式的DHA（2克/天）。采用ELISA试剂盒检测基线期（T0）和补充后（T1）的血浆消退素D1和D2水平。 结果：基线期乳腺癌患者的血浆消退素D1水平显著高于对照组（中位数21.3 vs. 7.3 pg/mL，p=0.039），消退素D2水平无显著差异。补充DHA后，BRCA1/2突变患者的消退素D1和D2均显著升高（分别增加185.8%和101.2%，p=0.037，p=0.028）。相反，家族性乳腺癌组的消退素D1显著下降（p=0.015）。与Ki67高表达患者相比，Ki67低表达患者的消退素D2水平随时间推移增幅更大（p=0.046）。 结论：DHA补充可调节乳腺癌患者消退素水平，其中BRCA1/2突变患者显著升高，提示其促炎症消退反应增强。家族性乳腺癌组消退素D1的降低则提示可能存在反应失调。这些发现表明消退素有望成为炎症消退的生物标志物及乳腺癌治疗的新靶点。
肿瘤(癌症)患者之家