Breast Cancer Genetic and Molecular Subtype Impacts Response to Omega-3 Fatty Acid Ethyl Esters

ABSTRACT

Epidemiological studies have correlated frequent omega-3 (n-3) fatty acid consumption with a lower risk for breast cancer; however, recent prospective studies have been less conclusive. Efforts in the preventive setting have focused on the use of n-3 fatty acids, and the pharmaceutical ethyl esters (EE) of these natural compounds, for high-risk patient populations. Limited understanding of specific mechanisms by which these agents function has hampered identification of the cancer subtype(s) that would gain the greatest therapeutic benefit. In this study, we investigated the in vitro effects of n-3 EEs in four distinct breast cancer subtypes and explored how they affect not only breast cancer cell survival but also modulate the nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) and peroxisome proliferator-activated receptor gamma signaling pathways. Similar to the high variance in response observed in human studies, we found that the effectiveness of n-3 EEs depends on the molecular characteristics of the MCF-7, CAMA-1, MDA-MB-231, and SKBR3 breast cancer cell lines and is closely associated with the suppression of NF-κB. These data strongly suggest that the use of n-3 fatty acids and their pharmaceutical ether esters in the prevention and therapeutic setting should be guided by specific tumor characteristics.

Declaration of interests

The authors declare that they have no competing interests.

Acknowledgments

Ching Hui Chen performed the experiments, helped with the design of the study, and drafted the manuscript. Carol Fabian and Stephen Hursting participated in the design of the study and reviewed the manuscript. Linda A. deGraffenried conceived the study, participated in its design and coordination, and reviewed the manuscript. All authors read and approved the final manuscript.

Funding

Ching Hui Chen was supported by the Breast Cancer Research Program of the Congressionally Directed Medical Research Programs Predoctoral Traineeship Award (Award Number W81XWH-11-1-0102).