Linoleic acid, an omega-6 fatty acid abundant in most vegetable oils, has previously been reported to promote triple negative (ER-/PR-/HER2-) breast cancer. Now a new study has uncovered the mechanism of action by which this occurs and confirmed the tumor-promoting effect of linoleic acid in an animal model of triple negative breast cancer.
Linoleic acid can promote breast cancer
A low dietary omega-6 to omega-3 fatty acid ratio has been linked to reduced breast cancer risk. Several studies have reported that breast cancer patients have higher levels of omega-6 fatty acids in their breast tissue than cancer-free women. Daughter mice of female mice fed a high linoleic acid diet are more prone to develop mammary tumors than control mice. Note that linoleic acid should not be confused with the beneficial omega-3 fat alpha-linolenic acid.
Exposure to linoleic acid has been demonstrated to induce pro-angiogenic activity in triple negative cells. Linoleic acid is metabolized into arachidonic acid in the body. Arachidonic acid has been reported to promote the migration (one of the early steps in metastasis) and invasion (penetration into neighboring non-cancerous tissues) of triple negative breast cancer cells.
Dietary sources of linoleic acid
Below are common cooking oils with substantial levels of linoleic acid as a percentage of total fat:
| Cooking oil | Linoleic acid |
|---|---|
| Safflower oil | 71% to 75% |
| Sunflower oil | 53% to 66% |
| Corn oil | 55% to 59% |
| Soybean oil | 51% to 56% |
Better choices are olive oil (7% to 15% linoleic acid) and canola oil (19% to 26%). Note that the breast cancer-linoleic acid connection is not straightforward since omega-6 fats are essential to health. The ratio of omega-6 to omega-3 fats (such as docosahexaenoic acid (DHA) found in fatty fish or alpha-linolenic acid in flaxseed oil) appears to be more important than the absolute amounts of these fats in the diet.
Latest research explains harmful effect of linoleic acid
The study referenced above was designed to investigate the mechanism of action by which linoleic acid increases triple negative breast cancer cell growth and proliferation at the molecular level. Nutrients affect this machinery in part through the enzyme mechanistic target of rapamycin (mTOR). mTOR interacts with other proteins to form mTORC1 and mTORC2, which regulate aspects of metabolism. Since linoleic acid is an essential nutrient, the authors hypothesized that the mTOR pathway senses and is activated by its availability.
In fact, linoleic acid's effects on mTORC1 were found to depend on the amount of the chaperone fatty acid-binding protein 5 (FABP5) present. FABP5 binds to various fats, enabling them to transfer from the bloodstream into cells. A nutrient signaling mechanism involving mTORC1 and FABP5 was found to be activated by linoleic acid, ultimately resulting in heightened mTOR signaling and cell proliferation. Although FABP5 is frequently expressed, the amounts are amplified in some tumors. The authors found that FABP5 was increased more in tumors and serum from triple-negative than from hormone receptor positive (ER+/PR+) breast cancer.
The authors conducted extensive experiments using breast cancer cell lines and animals implanted with patient-derived xenograft tumors. It was found that linoleic acid could activate mTORC1, but only in models of triple negative breast cancer. Importantly, levels of FABP5 were shown to be significantly higher in triple negative compared to ER+/PR+ tumors. This was demonstrated by feeding the animals a diet enriched with safflower oil (an oil with high linoleic acid content), which was observed to promote triple negative tumor growth.
In summary, FABP5 and omega-6 polyunsaturated fatty acids (PUFAs) appear to trigger potentially harmful nutrient-driven signaling events. Both factors are elevated in the serum of newly diagnosed triple negative patients. The authors conclude that further nutritional studies that stratify patients based on FABP5 expression and triple negative status are warranted.
Please see our article on Foods to eat & avoid for triple negative breast cancer for more information.