Kelly Tran

Background: Breast cancer (BC) is one of the leading causes of death in women worldwide.¹ Incidence rates of breast cancer are increasing yearly, while mortality rates are decreasing.² Cancer originates from accumulated genetic mutations and/or epigenetic modifications leading to aberrant cell proliferation and growth. While early cancer detection and effective treatment are on an overall positive trajectory, there are still wide variations in outcome, depending on the type, subtype, grade, and stage of BC. Treatment options include chemotherapy (including highly specific targeted and directed approaches), radiation, and surgery.^{2, 3} Currently, triple-negative breast cancer has the fewest effective treatment options available, since it doesn’t express hormone receptors or HER2 proteins that can be targeted. More effective treatment options should be explored, such as increasing the efficacy of current treatment. Omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), found in fatty fish, have been shown to have preventative anticancer properties in some models. However, their use as potential treatment for breast cancer is an area of active research.

Objectives: In this narrative review, I investigated the use of omega-3 fatty acids, alone and in combination with traditional chemotherapy, as treatment for Luminal A and TN subtypes of BC.

Search Methods: PubMed was searched using the terms: “breast cancer”, “omega 3”, “chemotherapy”, “DHA”, and “EPA” from 2017 to 2025.

Results: Studies, both in vitro and in vivo, show that omega-3 fatty acids, DHA in particular, induced apoptosis in BC cells through increasing expression and levels of pro-apoptotic genes and proteins while decreasing anti-apoptotic genes and proteins.^{4, 5, 6, 7} Pro-apoptotic genes, including caspase-3, 8, 9, 10, BAX, BID, and Fas, were upregulated in cells and tumors while anti-apoptotic genes including Bcl-2, P-gp, TG-2, and survivin were downregulated.^{4, 5, 6, 7} Omega-3 was shown to induce apoptosis alone in MCF-7 cells, which are representative of the Luminal A subtype.^{4, 5} In another study, omega-3 induced apoptosis by resensitizing doxorubicin-resistant MCF-7 cells through increasing drug accumulation.⁴ Omega-3 was shown to increase the efficacy of traditional chemotherapy by inducing apoptosis in MDA-MB-231 cells, representative of the triple-negative subtype, as well as in tumor xenografts derived from these cells.⁶ Excised tumors from mice treated with omega-3 had weighed significantly less than from the control group. The beneficial effects of omega-3 in combination with chemotherapy, inducing apoptosis, were also shown in patient-derived xenografts.⁷ A clinical trial was conducted with 48 women who received chemotherapy with or without omega-3 supplementation. In this Phase II trial, omega-3 (1 g/day) increased the efficacy of chemotherapy compared to the control group who didn’t receive supplementation. It was found that markers of proliferation, Ki-67 and VEGF, decreased, while Progression-Free Survival and Overall Survival increased, showing the beneficial effects of omega-3.⁸

Conclusion: Studies have shown that use of omega-3 fatty acids shows promise in inducing apoptosis and increasing drug accumulation when administered “alongside” chemotherapeutic drugs, increasing their efficacy in vitro in breast cancer cells, and in vivo in tumors, including in patients in a clinical trial. As chemotherapy has known and serious side effects, increasing its efficacy could result in use of lower doses with fewer side effects. However, additional studies are needed to investigate other BC types, subtypes, grades, or stages, and to determine optimal dosage in patients.

Works Cited:

1. Giaquinto AN, Sung H, Newman LA, et al. Breast cancer statistics 2024. CA Cancer J Clin. 2024;74(6):477-495. doi:10.3322/caac.21863
2. Loibl S, Poortmans P, Morrow M, Denkert C, Curigliano G. Breast cancer [published correction appears in Lancet. 2021 May 8;397(10286):1710. doi: 10.1016/S0140-6736(21)00838-2.]. Lancet. 2021;397(10286):1750-1769. doi:10.1016/S0140-6736(20)32381-3
3. Katsura C, Ogunmwonyi I, Kankam HK, Saha S. Breast cancer: presentation, investigation and management. Br J Hosp Med (Lond). 2022;83(2):1-7. doi:10.12968/hmed.2021.0459
4. Crovella S, Ouhtit A, Rahman SM, Rahman MM. Docosahexaenoic Acid, a Key Compound for Enhancing Sensitization to Drug in Doxorubicin-Resistant MCF-7 Cell Line. Nutrients. 2023;15(7):1658. Published 2023 Mar 29. doi:10.3390/nu15071658
5. Xue M, Ge Y, Yu C, Zheng Z, He X, Zhao J. Apoptosis is induced by docosahexaenoic acid in breast cancer cells via death receptor and mitochondria-mediated pathways. Mol Med Rep. 2017;16(1):978-982. doi:10.3892/mmr.2017.6678
6. Newell M, Brun M, Field CJ. Treatment with DHA Modifies the Response of MDA-MB-231 Breast Cancer Cells and Tumors from nu/nu Mice to Doxorubicin through Apoptosis and Cell Cycle Arrest. J Nutr. 2019;149(1):46-56. doi:10.1093/jn/nxy224
7. Newell M, Goruk S, Mazurak V, Postovit L, Field CJ. Role of docosahexaenoic acid in enhancement of docetaxel action in patient-derived breast cancer xenografts. Breast Cancer Res Treat. 2019;177(2):357-367. doi:10.1007/s10549-019-05331-8
8. Darwito D, Dharmana E, Riwanto I, et al. Effects of Omega-3 Supplementation on Ki-67 and VEGF Expression Levels and Clinical Outcomes of Locally Advanced Breast Cancer Patients Treated with Neoadjuvant CAF Chemotherapy: A Randomized Controlled Trial Report. Asian Pac J Cancer Prev. 2019;20(3):911-916. Published 2019 Mar 26. doi:10.31557/APJCP.2019.20.3.911