Research report: Omega-3 fatty acids in aromatase inhibitor-associated dyslipidemia: mechanisms, clinical evidence, and future perspectives

Aromatase inhibitors such as anastrozole, letrozole, and exemestane are widely prescribed as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer. The authors, based at the Affiliated Hospital of Guangdong Medical University in Zhanjiang, China, argue that omega-3 fatty acids deserve closer scrutiny as a possible countermeasure, while cautioning that the clinical evidence is not yet sufficient.

The biological logic behind the concern centers on estrogen. Prolonged estrogen deprivation induced by aromatase inhibitor therapy appears to affect hepatic lipoprotein metabolism, and the review links the resulting lipid abnormalities to endothelial dysfunction, oxidative stress, and chronic inflammation. Because these mechanisms involve estrogen-dependent regulation of how the liver handles lipoproteins, the pattern of dyslipidemia may differ from that seen in other contexts, and the review emphasizes that individual aromatase inhibitors may not all exert identical lipid effects when compared with tamoxifen.

Omega-3 polyunsaturated fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are the review’s central candidates for intervention. These fatty acids have established effects on lipid metabolism and cardiovascular health, and the authors lay out their metabolic machinery in technical detail: activation of peroxisome proliferator-activated receptor-alpha, suppression of sterol regulatory element-binding protein-1c, modulation of hepatic very-low-density lipoprotein production, enhancement of fatty acid oxidation, and regulation of lipoprotein clearance.

Yet the review is notably careful about what omega-3s can and cannot do. The authors stress that the effects of EPA and DHA on LDL cholesterol, total cholesterol, and HDL cholesterol are less consistent than their well-documented triglyceride-lowering effects. These cholesterol effects may also differ according to formulation and dose, meaning that not every omega-3 product can be assumed to behave identically in patients taking aromatase inhibitors.

To assess applicability, the review summarizes clinical evidence from two distinct populations: general dyslipidemia patients and breast cancer patients. The authors then evaluate how far findings from these groups can be extended to women receiving aromatase inhibitor therapy. This translational step is where the review’s central caution emerges, because evidence generated in other populations does not automatically transfer to the specific metabolic setting of estrogen deprivation induced by endocrine therapy.

The bottom line, as stated by the authors, is that current evidence supports a strong biological rationale for omega-3 fatty acid supplementation but remains insufficient to establish its efficacy specifically for aromatase inhibitor-associated dyslipidemia. In other words, the mechanistic case is compelling, but no randomized trial evidence yet demonstrates that omega-3 supplementation improves cholesterol profiles or cardiovascular outcomes in this patient group.

To close that gap, the review outlines a research agenda for future randomized controlled trials. Such studies should directly evaluate lipid and cardiovascular outcomes rather than relying on surrogate reasoning, compare EPA- and DHA-containing formulations head to head, account for differences among individual aromatase inhibitors, and identify patient subgroups most likely to benefit from omega-3-based interventions.

The authors frame omega-3 fatty acids as a promising but unproven candidate, one whose triglyceride effects are well established while its cholesterol effects remain uncertain.

For now, the review’s contribution is a map rather than a prescription: a detailed account of the mechanisms linking aromatase inhibitor therapy to dyslipidemia, a synthesis of what is and is not known about EPA and DHA in cholesterol metabolism, and a clear statement of the trials still needed before omega-3 supplementation can be recommended for this indication.

Subject of Research: A review of mechanisms and clinical evidence for omega-3 fatty acids in dyslipidemia associated with aromatase inhibitor therapy in postmenopausal breast cancer patients.

Article Title: Omega-3 fatty acids in aromatase inhibitor-associated dyslipidemia: mechanisms, clinical evidence, and future perspectives

Article References: Chen, R., Xiong, M., & Huang, S. (2026). Omega-3 fatty acids in aromatase inhibitor-associated dyslipidemia: mechanisms, clinical evidence, and future perspectives. Frontiers in Oncology, 16, Article 1923962. https://doi.org/10.3389/fonc.2026.1923962

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1923962

Keywords: aromatase inhibitors, omega-3 fatty acids, EPA, DHA, breast cancer, dyslipidemia, cholesterol, cardiovascular risk, endocrine therapy, postmenopausal women, Omega-3, fatty