Not only did oleic acid suppress over-expression of a gene associated with highly aggressive tumors, it also boosted the effectiveness of an antibody that targets the gene and has helped to prolong the lives of many breast cancer patients.

Suppresses Oncogene, Boosts Antibody

The researchers have demonstrated in a series of laboratory experiments on breast cancer cell lines that oleic acid dramatically cuts the levels of an oncogene called Her-2/neu, also known as erb B-2. High levels of Her-2/neu occur in over a fifth of breast cancer patients and are associated with highly aggressive tumors that have a poor prognosis.

Not only did oleic acid suppress over-expression of the gene, other tests on the cell lines showed that it also boosted the effectiveness of trastuzumab (Herceptin), the monoclonal antibody treatment that targets the Her-2/neu gene and has helped to prolong the lives of many breast cancer patients.

Promotes Death of Breast Cancer Cells

"Our findings underpin epidemiological studies that show that the Mediterranean diet has significant protective effects against cancer, heart disease and ageing," says lead researcher, Dr. Javier Menendez, assistant professor at the Northwestern University Feinberg School of Medicine in Chicago and a research scientist with the Evanston Northwestern Healthcare Research Institute.

The strongest evidence that monounsaturated fatty acids such as oleic acid may influence breast cancer risk comes from studies of southern European populations, but animal research to date has thrown up inconsistent results, possibly because olive oil has been administered as a mixture of several fatty acids and other natural protections and not on its own.

"To our knowledge, this is the first report that a dietary monounsaturated fatty acid previously suggested to be protective against breast cancer significantly down-regulates the expression of Her-2/neu, cutting it by up to 46 percent. Her-2/neu is one of the most important oncogenes in breast cancer," said Dr. Menendez. "Moreover, in our tests, oleic acid's inhibition of Her-2/neu synergistically interacted with Herceptin-based immunotherapy by promoting the death of breast cancer cells exhibiting high levels of the oncogene.

"Additionally, alongside the sensitising effect of oleic acid on the efficacy of Herceptin we found it increased the expression of a protein (p27Kip1), a tumor suppresser protein, which is implicated in the development of resistance to Herceptin treatment."

Molecular Mechanisms

Dr. Menendez said that his team's findings should not only help in understanding the molecular mechanisms by which individual dietary fatty acids regulate the malignant behavior of breast cancer cells, but also suggested that dietary interventions based on oleic acid may delay or prevent Herceptin resistance in Her-2/neu-postive breast cancer patients.

Dr. Menendez and co-researchers Dr. Ruth Lupu, director of the Evanston Northwestern Health Research Institute's Breast Cancer Translational Program and Dr Ramon Colomer, head of the Medical Oncology Division at Institut Catala d' Oncologia in Girona, Spain, are now looking to identify the ultimate molecular mechanism through which oleic acid supplementation inhibits the expression of Her-2/neu, as its blocking action appears to work in a different way from that of Herceptin.

Future Studies

They are also seeking funds for a study to see whether a high virgin olive oil diet will modulate the expression of the Her-2/neu oncogene in human breast tumors in animals and make the tumors less aggressive. In addition, they want to investigate whether oleic acid-rich diets have any effect on the anti-tumor activity of Herceptin.

Dr. Menendez emphasised that while it was important to be cautious about the implications of the study, as laboratory results did not always translate into clinical practice, their findings did present the concept that a higher level of oleic acid in breast tissue could provide an effective means of influencing the outcome of breast cancer in patients carrying high levels of the rogue gene.

"They may also help in designing future epidemiological studies and, eventually, dietary counselling to delay or prevent drug resistance developing in patients taking Herceptin," he said.