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BioMed Research International
Volume 2015, Article ID 638645, 10 pages
Review Article

Combination of Antiestrogens and Omega-3 Fatty Acids for Breast Cancer Prevention

1Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
2Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
3Colorado State University, Cancer Prevention Laboratory, Collins, CO 80523, USA
4The Irma H. Russo MD Breast Cancer Research Laboratory, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA 19111, USA
5Barretos School of Health Sciences, Dr. Paulo Prata-FACISB, 14784-400 Barretos, SP, Brazil
6Molecular Oncology Research Center, Barretos Cancer Hospital, 14784-400 Barretos, SP, Brazil

Received 25 September 2014; Accepted 23 December 2014

Academic Editor: Kyu Lim

Copyright © 2015 Andrea Manni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The molecular and biological heterogeneity of human breast cancer emphasizes the importance of a multitargeted approach for effective chemoprevention. Targeting the estrogen receptor pathway alone with the antiestrogens, Tamoxifen and Raloxifene reduces the incidence of estrogen receptor positive tumors but is ineffective against the development of hormone independent cancers. Our preclinical data indicate that the administration of omega-3 fatty acids potentiates the antitumor effects of Tamoxifen by inhibiting multiple proliferative and antiapoptotic pathways, several of which interact with estrogen receptor signaling. The complementarity in the mechanism of antitumor action of Tamoxifen and omega-3 fatty acids is well supported by our signaling, genomic, and proteomic studies. Furthermore, administration of omega-3 fatty acids allows the use of lower and, hence, likely less toxic doses of Tamoxifen. If these findings are supported in the clinical setting, the combination of omega-3 fatty acids and anteistrogens may emerge as a promising, effective, and safe chemopreventive strategy to be tested in a large multi-institutional trial using breast cancer incidence as the primary endpoint.