Munhoz Jaqueline, Newell Marnie, Goruk Susan, Ghosh Sunita, Patel Dhruvesh, Joy Anil Abraham, Bigras Gilbert, Mazurak Vera, Courneya Kerry S, Hemmings Denise G, Field Catherine J
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
Department of Oncology, University of Alberta, Edmonton, T6G 1Z2, Canada.
Breast Cancer Res. 2025 May 22;27(1):91. doi: 10.1186/s13058-025-02048-z.
Breast cancer neoadjuvant therapy may negatively impact the immune system. As a secondary outcome of the docosahexaenoic acid (DHA) for women with breast cancer in the neoadjuvant setting (DHA-WIN trial), we sought to assess the effects of an intervention with DHA on parameters of immune function of women undergoing neoadjuvant therapy.
Women with early-stage breast cancer in the neoadjuvant setting were recruited for the DHA-WIN trial and randomly assigned to receive either 4.4 g/day of DHA or a placebo for 18 weeks in conjunction with their neoadjuvant chemotherapy for breast cancer. Venous blood was collected to isolate peripheral blood mononuclear cells. Immune parameters were assessed by measuring white blood cell concentration, flow cytometry, and cytokines concentration after mitogen-stimulated immune response.
In the placebo group the proportion of T cells (CD3 +), and functionally active monocytes (CD14 + HLA-DR +) was reduced at the last cycle of chemotherapy (15 weeks) but remained constant in the DHA group (P interaction < 0.05). The neutrophil-to-lymphocyte ratio (NLR) was maintained in the DHA group but increased in the placebo at the end of chemotherapy (P-interaction = 0.02). An increase in this ratio was associated with lower chance of achieving pathological complete response (OR = 0.32, 95% CI [0.14,0.16], P = 0.01). After 15 weeks of therapy, the DHA-supplemented group had higher concentrations of stimulated cytokines IL-4, IL-10, and the T helper type 1 cytokine IFN-γ after phytohemagglutinin (PHA) challenge, and higher concentrations of TNF-α and IFN-γ cytokines after lipopolysaccharide exposure (P < 0.05).
Supplementing DHA during breast cancer neoadjuvant chemotherapy improved systemic immune function by attenuating changes in blood cell concentrations, preventing depletion of immune cells, and enhancing ex vivo cytokine secretion after stimulation.
乳腺癌新辅助治疗可能会对免疫系统产生负面影响。作为新辅助治疗中二十二碳六烯酸（DHA）用于乳腺癌女性的次要结果（DHA-WIN试验），我们试图评估DHA干预对接受新辅助治疗女性免疫功能参数的影响。
新辅助治疗的早期乳腺癌女性被纳入DHA-WIN试验，并随机分配接受4.4克/天的DHA或安慰剂，为期18周，同时接受乳腺癌新辅助化疗。采集静脉血以分离外周血单核细胞。通过测量白细胞浓度、流式细胞术以及丝裂原刺激免疫反应后的细胞因子浓度来评估免疫参数。
在安慰剂组中，化疗最后一个周期（15周）时T细胞（CD3 +）和功能活跃单核细胞（CD14 + HLA-DR +）的比例降低，但DHA组保持不变（P交互作用<0.05）。DHA组中性粒细胞与淋巴细胞比值（NLR）保持稳定，而安慰剂组在化疗结束时升高（P交互作用=0.02）。该比值升高与达到病理完全缓解的几率降低相关（OR = 0.32，95%CI [0.14,0.16]，P = 0.01）。治疗15周后，补充DHA组在植物血凝素（PHA）刺激后，刺激细胞因子IL-4、IL-10以及1型辅助性T细胞细胞因子IFN-γ的浓度更高，在脂多糖暴露后TNF-α和IFN-γ细胞因子的浓度更高（P < 0.05）。
在乳腺癌新辅助化疗期间补充DHA可通过减弱血细胞浓度变化、防止免疫细胞耗竭以及增强刺激后体外细胞因子分泌来改善全身免疫功能。
