The Effects of Omega-3 Polyunsaturated Fatty Acids on Breast Cancer as a Preventive Measure or as an Adjunct to Conventional Treatments

Nutrients · 11 authors, 2 centres

AI SUMMARY

FIDELITY 93%

POPULATIONAnimal models (mice and rats) with induced breast cancer — including xenograft, allograft, transgenic, and chemically induced models; predominantly female (83%), aged 3–8 weeks.

INTERVENTIONDietary supplementation with ω-3 PUFAs (EPA, DHA, ALA) alone or combined with antitumor drugs (docetaxel, doxorubicin, paclitaxel, rapamycin, dasatinib, etc.), administered orally (in diet or gavage) for 3 weeks to 5 months.

COMPARISONControl groups receiving standard diet, ω-6 PUFA-enriched diet, vehicle, or antitumor drug alone.

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AGENT 01 · STRUCTURED SUMMARY

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TL;DR

This systematic review of 27 preclinical studies (2017–2022) found that omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation, particularly when combined with conventional chemotherapy, reduces tumor growth and weight, delays tumor incidence, and improves survival in animal models of breast cancer. The most consistent benefits were seen in triple-negative breast cancer models, with combined ω-3 PUFA plus drug therapy achieving up to 87% reduction in early tumor growth and a mean survival increase of 23 days. These findings support ω-3 PUFAs as a promising adjunct to standard breast cancer treatment, though optimal dosing remains unclear.

Full summary

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**Background:** Breast cancer (BC) is the second most common neoplasm worldwide, with 2.3 million new cases in 2020 and an expected rise to over 3 million cases by 2040. Current treatments (surgery, chemotherapy, radiotherapy, hormone therapy, immunotherapy) have significant side effects that impact quality of life and treatment adherence. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have shown preclinical promise as supportive therapeutic agents by reducing inflammation, modulating cell proliferation, inducing apoptosis, and inhibiting angiogenesis. This systematic review evaluated the last 5 years of preclinical evidence on ω-3 PUFAs for BC prevention and treatment.

**Methods:** A systematic search was conducted in PubMed and Scopus for articles published between June 2017 and September 2022, following PRISMA guidelines. The search strategy used Boolean operators with keywords for omega-3 fatty acids and breast cancer, excluding clinical trials, meta-analyses, reviews, and non-English publications. Inclusion criteria required original full-text articles using animal models of BC (transgenic, tumor cell induction, or chemical induction) to evaluate dietary ω-3 PUFA enrichment for prevention or treatment, with or without antitumor drugs. Eleven authors independently screened titles/abstracts, and five authors selected final articles. Data were extracted on experimental design, diet characteristics, tumor induction methods, and outcomes. Risk of bias was assessed by paired review with third-author adjudication.

**Results:** From 679 initial records (216 PubMed, 463 Scopus), 27 studies met inclusion criteria. The most common BC induction model was tumor cell transplantation (69%), followed by transgenic models (17%) and chemical induction (14%). Murine models were used in 93% of studies (primarily Balb/c mice, 57%) and rats in 7%. Triple-negative BC (TNBC) cells were used in 80% of cell-transplant studies, predominantly MDA-MB-231 cells (35%). Dietary ω-3 PUFA sources included fish oil (29.6%), menhaden oil (11.1%), chia oil (7.4%), flaxseed oil (7.4%), and DHAsco (14.8%). The three most used ω-3 types were ALA, DHA (each 63%), and EPA (44.4%). Combined ω-3 PUFA plus antitumor drug treatment was evaluated in 55.6% of studies. Key outcomes: combined treatment achieved the highest early tumor growth reduction (mean 77%, maximum 87% within 15 days) and tumor weight reduction (mean 57%, maximum 86%). ω-3 PUFA-enriched diet alone (higher ω-3 than ω-6) showed a mean tumor incidence delay of 20% at 50% animal-affection and 12% at 100% affection. Tumor latency (T50) showed a mean delay of 19 days (range 7–50 days). Metastasis reduction was 70% with combined treatment (range 61–84%) versus 37% with ω-3 PUFA alone (range 14–70%). Survival increased by a mean of 23 days (range 5–45 days) with combined treatment and 20 days with ω-3 PUFA alone. Molecular analyses focused on proliferation, apoptosis, inflammation, angiogenesis (VEGF), and immune checkpoint pathways.

**Clinical Implications:** This systematic review provides preclinical evidence that ω-3 PUFA supplementation, especially combined with conventional chemotherapy, enhances antitumor efficacy by reducing tumor burden, delaying progression, and improving survival in BC models. The benefits were most pronounced in TNBC models, which are clinically the most aggressive subtype with limited targeted therapy options. The findings support the potential of ω-3 PUFAs as a safe, accessible adjunct to standard BC treatment, potentially reducing chemotherapy side effects and improving outcomes. However, significant heterogeneity in experimental designs, ω-3 doses, and outcome measures precludes determination of an optimal therapeutic dose. The authors note that clinical studies have shown ω-3 PUFA supplementation reduces Ki-67 and VEGF expression in BC patients. Future research should focus on standardizing ω-3 dosing regimens and evaluating long-term effects in well-designed clinical trials.

PICO

PPOPULATION

Animal models (mice and rats) with induced breast cancer — including xenograft, allograft, transgenic, and chemically induced models; predominantly female (83%), aged 3–8 weeks.

IINTERVENTION

Dietary supplementation with ω-3 PUFAs (EPA, DHA, ALA) alone or combined with antitumor drugs (docetaxel, doxorubicin, paclitaxel, rapamycin, dasatinib, etc.), administered orally (in diet or gavage) for 3 weeks to 5 months.

OOUTCOME

Tumor growth/volume, tumor weight, animal weight, tumor incidence, tumor latency, metastasis, survival rate, and molecular/histological markers (apoptosis, proliferation, angiogenesis, inflammation).

STUDY TYPE

systematic_review

SPECIALTY

oncology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

93% · A

ORIGINAL PAPER

PMC10052714

The Effects of Omega-3 Polyunsaturated Fatty Acids on Breast Cancer as a Preventive Measure or as an Adjunct to Conventional Treatments

Nutrients

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ABSTRACT

Abstract In order to understand how omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplements affect breast cancer prevention and treatment, a systematic review of articles published in the last 5 years in two databases was performed. Of the 679 articles identified, only 27 were included and examined based on five topics, taking into account: the induction type of the breast cancer used in animal models; the characteristics of the induction model by cell transplantation; the experimental design of the ω-3 supplementation—combined or not with a treatment antitumor drug; the fatty acids (FAs) composition used; the analysis of the studies’ outcomes. There are diverse and well-established animal models of breast cancer in the literature, with very relevant histological and molecular similarities depending on the specific objective of the study, such as whether the method of tumor induction was transgenic, by cell transplantation, or by oncogenic drugs. The analyses of outcomes were mainly focused on monitoring tumor growth, body/tumor weight, and molecular, genetic, or histological analyses, and few studies evaluated latency, survival, or metastases. The best results occurred when supplementation with ω-3 PUFA was associated with antitumor drugs, especially in the analysis of metastases and volume/weight of tumors or when the supplementation was started early and maintained for a long time. However, the beneficial effect of ω-3 PUFA supplementation when not associated with an antitumor agent remains unclear. Keywords: omega-3, breast cancer, preclinical, docosahexaenoic acid, polyunsaturated fatty acids, EPA, DHA

CITATION EXPORT

Matheus H Theinel, Mariana P Nucci, Arielly H Alves et al.. The Effects of Omega-3 Polyunsaturated Fatty Acids on Breast Cancer as a Preventive Measure or as an Adjunct to Conventional Treatments. Nutrients. (2023). https://doi.org/10.3390/nu15061310

AUTHORS

11 · 2 CENTRES

Matheus H Theinel, Mariana P Nucci, Arielly H Alves, Olivia F M Dias, Javier B Mamani, Murilo M Garrigós, Fernando A Oliveira, Gabriel N A Rego, Nicole M E Valle, Gabriela Cianciarullo, Lionel F Gamarra

1Hospital Israelita Albert Einstein, São Paulo 05652-000, Brazil
2LIM44–Hospital das Clínicas da Faculdade Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil