Safety and efficacy of docosahexaenoic acid supplementation during neoadjuvant breast cancer therapy: Findings from the phase II, double-blind, randomized controlled DHA-WIN trial

Document Type

Article

Publication Date

10-1-2025

Publication Title

International journal of cancer

Abstract

There is limited clinical evidence of docosahexaenoic acid (DHA) efficacy during breast cancer neoadjuvant chemotherapy (NAC). This randomized, double-blind, placebo-controlled trial aimed to investigate the safety and efficacy of DHA supplementation in breast cancer patients undergoing NAC. Participants (n = 49) were assigned to receive either DHA 4.4 g/day orally (algae triacylglycerol) or a placebo (corn/soy oil) over six cycles (18 weeks) of NAC. The primary outcome was the evaluation of changes in the percentage of Ki-67 expression, assessed by immunohistochemistry analysis from pre- to post-treatment. Secondary outcomes included pathological complete response, incidence of adverse effects, and 3-year survival analysis. Compliance was evaluated by fatty acid analysis of plasma phospholipids and erythrocyte total lipids quantified by gas-liquid chromatography. The expression of Ki-67 significantly decreased in both groups, with no significant effects of the DHA intervention (p = 0.38). When stratified by breast cancer subtype, there was a trend of greater reduction in Ki-67 expression in the human epidermal growth receptor 2 (HER2+++) subtype in the DHA group compared to placebo (p = 0.1). The % of DHA in erythrocytes and plasma phospholipids was increased by two-fold at 9 and 15 weeks of therapy in the DHA group, while it remained unchanged in the placebo group (p-interaction < 0.001). There was no reported incidence of adverse effects related to the intervention, and no significant effects were found in the other secondary outcomes. NAC significantly decreased the expression of Ki-67, with no additional beneficial effects observed by DHA supplementation. Further research is necessary to confirm these findings.

Medical Subject Headings

Humans; Female; Docosahexaenoic Acids/administration & dosage/adverse effects/therapeutic use; Breast Neoplasms/drug therapy/pathology; Double-Blind Method; Neoadjuvant Therapy/methods; Middle Aged; Dietary Supplements; Adult; Ki-67 Antigen/metabolism; Aged; Treatment Outcome; Ki‐67; Omega‐3; human epidermal growth factor receptor 2; long‐chain polyunsaturated fatty acids; pathological complete response; triple negative breast cancer

PubMed ID

40490846

ePublication

ePub ahead of print

Volume

157

Issue

7

First Page

1405

Last Page

1419

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