P Bougnoux
INSERM U921 & Cancéropôle Grand-Ouest, Centre Henry S. Kaplan, Tours, France

The rationale for increasing the activity of anticancer treatments through a dietary intervention results from a body of circumstantial facts: i) sensitivity of breast cancer cells to anticancer chemotherapy can be increased when cell membranes are enriched with docosahexaenoic acid (DHA); ii) sensitivity of experimental, autochtoneous rat mammary tumors to anticancer drugs is substantially enhanced by a dietary intervention with fish oil or DHA, and this observation also applies to ionizing radiation; iii) in humans, during neoadjuvant chemotherapy for large breast malignant tumors, the efficacy of anticancer drugs on the tumors is greater in patients with elevated DHA level in adipose tissue than in patients with low DHA; iv) we recently carried out a dietary DHA intervention trial in metastatic breast cancer patients, and found survival to be increased when DHA was incorporated, thus documenting the feasibility, safety and interest of this approach during chemotherapy.

Dietary polyunsaturated fatty acids such as DHA integrate into cells, leading to an enrichment of their membrane phospholipids. Targets for their actions have been individualized both in vitro and in vivo. These include a direct action at the cell membrane, or an indirect effect through their peroxidizability. DHA may alter cell antioxidant defenses through the regulation of the transcription of their genes. Peroxidation of these highly unsaturated fatty acids by the oxidative stress resulting from chemotherapy leads to deep alterations of cellular pharmacodynamics of anthracyclines. It also destabilizes membranes of cell organelles such as mitochondria, which may amplify cell death. DHA integrates into endothelial cells, translating in an increase in tumor microvessels permeability with subsequent entrance of oxygen and anticancer drugs. The integration of these fatty acids into other cells within the tumor microenvironment may account for the multiplicity of their effects on the host, whose nutritional status appears as a determinant of tumor sensitivity to anticancer agents. Clinical trials are needed to precisely evaluate the role of these dietary fatty acids in breast cancer treatments.

Keywords: Fatty acids, breast cancer, lcPUFA, DHA, chemotherapy
Schlüsselwörter: Omega-3 Fettsäuren, Brustkrebs, lcPUFA, DHA, Chemotherapie