Researchers have uncovered reasons why the Mediterranean diet, with its high intake of oleic acid-rich olive oil, seems to protect against breast cancer. They have also found evidence that oleic acid may have a future role in treatment. The findings were reported in the journal Annals of Oncology.

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.

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, said: "Our findings underpin epidemiological studies that show that the Mediterranean diet has significant protective effects against cancer, heart disease and ageing."

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%. Her-2/neu is one of the most important oncogenes in breast cancer," said 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 sensitizing 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."

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.

Menendez emphasized 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 counseling to delay or prevent drug resistance developing in patients taking Herceptin," he said.

SOURCE:
Annals of Oncology, January 10, 2005