The present study was designed to investigate the influence of oleic acid on breast cancer cell invasiveness. Both animal studies and population studies have reported associations between dietary fatty acids and increased risk of developing breast cancer. Obesity, which is characterized by high cholesterol, high triglycerides, and an elevated level of circulating free fatty acids, is also associated with increased risk of cancer. In breast cancer cells, the free fatty acid oleic acid has been shown to induce migration and proliferation, as well as prolonging survival, and invasion, and increasing in cellular Ca(2+) concentration, MEK1/2, ERK1/2, FAK and Src activation. However, the role of oleic acid on matrix metalloproteinase-9 (MMP-9) secretion and invasion has not been studied in detail. MMPs are enzymes essential for the degradation of most components of the extracellular matrix (the non-cellular portion of tissues which provides structural support to the cells), and thereby have a role in multiple biological processes, including inflammation, infection, and tumor invasion and metastasis. In the study, the authors used gelatin zymography assays to demonstrate that stimulation of MDA-MB-231 breast cancer cells with 200 muM oleic acid induces an increase in MMP-9 secretion through a PKC, Src, and EGFR-dependent pathway. In addition, it was found that microtubule network mediates MMP-9 secretion induced by oleic acid. On the other hand, oleic acid does not bring about an increase in MMP-9 secretion in non-cancerous breast cells. Furthermore, although oleic acid induces invasion through an EGFR, Gi/Go proteins, MMPs, PKC and Src-dependent pathway, it is not able to promote invasion in non-invasive MCF-7 breast cancer cells. The authors conclude that oleic acid promotes an increase in MMP-9 secretion and invasion through a PKC, Src, and EGFR-dependent pathway in breast cancer cells.

The present study was designed to determine the optimal dietary omega-6 to omega-3 (n-6/n-3) fatty acid ratio for breast cancer prevention in an animal model. Although consumption of omega-3 fatty acids has been reported to be beneficial in preventing breast cancer, the optimal n-6/n-3 ratio has not been established. Both n-6 and n-3 fatty acids are essential for normal development and biological functioning. However, both also have metabolizing enzymes in common and have the potential to antagonize each other’s metabolism thereby. In the study, experiments were performed to determine the ratio or ratios of dietary n-6/n-3 that are optimal for chemoprevention while at the same time avoiding adverse effects on normal development. Mammographic density was used as a surrogate marker for breast cancer risk. Groups of nine 32-day old female Sprague Dawley rats were randomly assigned to one of seven dietary regimens with n-6/n-3 ratios as follows: 25:1, 10:1, 5:1, 1:1, 1:5, 1:10, and 1:25. The overall proportion of calories from fat was fixed at 30% across all seven diets. Rat mammary gland density was measured using digital analyses of abdominal-inguinal mammary gland whole mounts stained with alum carmine. Density was estimated using either area or integrated optical density and reported as percentage of the mammary gland fat pad occupied by mammary epithelium. Density was found to be unaffected in the high n-6 group of the study; in other words, a high omega-6 diet did not induce any increase in density. However, mammary gland density was found to be significantly reduced in the high omega-3 group (16%, p<0.03). The authors comment that they are in the process of determining (1) whether reduced mammary gland density is accounted for by effects on the cell cycle or by induction of a pro-apoptotic environment; (2) the extent to which these effects are influenced by altered signaling via activated protein kinase B (Akt); and (3) the mechanism of action by which the n-6/n-3 ratio alters eicosanoid-mediated bioactivity.

The present study was designed to investigate the effect of increasing the ratio of omega-3 to omega-6 fats in the maternal diet of rats on the risk of breast cancer of their female offspring. Maternal consumption of a diet high in omega-6 polyunsaturated fats has been shown to increase risk of mammary gland cancer in female offspring of rats whereas a diet high in omega-3 polyunsaturated fats from fish oil has been shown to reduce the risk. In the study, omega-3 polyunsaturated fats were increased compared to omega-6 polyunsaturated fats by using canola oil instead of corn oil in the maternal diet. Female SV 129 mice were placed into one of two groups. The first group was placed on a control diet containing 10% by weight corn oil. Corn oil contains 50% omega-6 polyunsaturated fats. The second group received 10% by weight canola oil. Canola oil consists of 20% omega-6 polyunsaturated fats and 10% omega-3 polyunsaturated fats. After two weeks, the rats on the diets were mated with homozygous C3(1) TAg transgenic mice. The female mice continued to consume their assigned diets throughout pregnancy and nursing of the pups. After weaning, all of the female pups were given the high omega-6 corn oil diet. On a standard corn oil diet, female offspring would be expected to develop mammary gland tumors by six months of age. Compared to offspring of mothers fed the corn oil diet, pups of mothers fed the canola oil diet had significantly fewer mammary gland tumors throughout the experiment. At 130 days of age, the offspring of the canola oil diet group had significantly fewer tumors per mouse (multiplicity). Tumor incidence (fraction of mice with any tumors) and total tumor weight per mouse (in mice that developed any tumors) in the offspring of the canola oil diet group was less than half that of the corn oil diet group. At 170 days of age, the total tumor weight per mouse was significantly less in the canola oil diet pups and if a tumor did develop, the rate of tumor growth rate was half that of corn oil diet group. In other words, maternal consumption of canola oil was associated with delayed appearance of mammary gland tumors and slowed the growth of any tumors that developed in the offspring. The authors conclude that substituting canola oil for corn oil is an easy dietary change for people to make that might decrease risk of breast cancer in their daughters.

The present study was designed to investigate the effects of canola oil on breast cancer cell growth and apoptosis. It has been suggested that the protective effect on breast cancer risk of omega-3 fatty acids depends in part on the relative level of omega-6 fatty acids, with a recommended omega-6 to omega-3 ratio of two to one or lower. With a saturated fat content of about 7% of total fat (approximately half the level in corn oil, olive oil and soybean oil), canola oil has a low level of saturated fat. Canola oil also has a relatively high level of the monounsaturated fatty acid oleic acid (62%) and omega-3 fatty acids (alpha-linolenic acid, 10%) compared to most vegetable oils. It is thought that the combination of low saturated fat, high oleic acid, and relatively high omega-3 fatty acid content in canola oil is responsible for its healthful properties. In the study, two estrogen receptor-positive (ER+) breast cancer cell lines, T47D and MCF-7, and a non-cancerous mammary cell line, MCF-10A, were cultured. Cell proliferation and caspase-3 and p53 activities were measured under supplementation with canola oil and without it. Canola oil supplementation was found to significantly inhibit the growth of both T47D and MCF-7 breast cancer cells, but not the normal MCF-10A cell line. Canola oil also significantly increased the expression of p53 and the activity of caspase-3 enzyme. The tumor suppressor gene p53 is involved in cancer cell death and caspase-3 enzyme is one of the crucial enzymes regulating apoptosis. The authors comment that these results could be useful in the development of improved nutritional strategies for breast cancer prevention.

This San Francisco Bay area study examined the association between fat intake and use of fat in cooking and the risk of breast cancer in a population-based, multiethnic, case-control study. A food frequency questionnaire was used among 2,045 controls and 1,703 breast cancer cases diagnosed between 1995 and 1999. Preferred use of fat for cooking was also determined. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). High fat intake was found to be associated with increased risk of breast cancer (highest vs. lowest quartile, adjusted OR = 1.35, 95% CI = 1.10-1.65). A positive association was found for oleic acid (OR = 1.55, 95% CI = 1.14-2.10, P(trend) < 0.01) but not for linoleic acid or saturated fat. Increased risk was found for women cooking with hydrogenated fats (OR = 1.58, 95% CI = 1.20-2.10) or vegetable/corn oil (rich in linoleic acid; OR = 1.30, 95% CI = 1.06-1.58) compared to women using olive/canola oil (rich in oleic acid). The authors conclude that a low-fat diet may play a role in breast cancer prevention. They further speculate that monounsaturated trans fats may have driven the discrepant associations between types of fat and breast cancer.

The present prospective population study was designed to evaluate how dietary intakes of total fat, monounsaturated fat, polyunsaturated fat and saturated fat were associated with breast cancer risk. The study also sought to answer whether any associations differed by estrogen or progesterone receptor status. 49,261 Swedish women aged 30 to 49 years were enrolled in the study and there were 974 breast cancer cases by December 2005. Total fat, monounsaturated fat, polyunsaturated fat and saturated fat were found not to be associated with overall risk of breast cancer. However, women in the highest quintiles of intake of monounsaturated fat and polyunsaturated fat were found to have a reduced breast cancer risk after age 50 (hazard ratios 95% confidence interval = 0.45: 0.25–0.99 and 0.54: 0.35–0.85, respectively) compared to women in the lowest quintiles. These associations did not vary by estrogen or progesterone receptor status. The authors conclude that despite the lack of associations before age 50, the type of fat consumed during premenopausal years may have later differential effects on risk.

The present study was designed to investigate the possible anticlastogenic effects of pretreatment with olive, extra virgin olive, canola or corn oil on cisplatin-induced chromosomal aberrations in a rat model. Cisplatin is a widely used antineoplastic drug which is sometimes used for treatment of triple negative breast cancer (estrogen receptor negative, progesterone receptor negative, and not HER2 overexpressing), but its clastogenic potential is of concern (clastogenic agents induce breakages in chromosomes). Genetic damage has been observed during chemotherapy or many years later in patients receiving long-term treatment with cisplatin. In the study, Wistar rats were pretreated with olive, extra virgin olive, canola or corn oil a single dose (5 ml/kg body weight) by gavage before receiving cisplatin. The animals were sacrificed 24 hours after the cisplatin injections. Pretreatment with a single dose of olive, extra virgin olive or canola oil (but not corn oil) resulted in statistically significant declines in total of chromosomal aberrations and abnormal metaphases compared to the animals treated with cisplatin alone. The authors conclude that these oils have some antioxidant effect, but that the anticlastogenesis mechanisms of these oils need to be explored further before their use during cisplatin chemotherapy.

The present French case-control study was designed to test the hypothesis that omega-3 (n-3) fatty acids protect against breast cancer by examining the fatty acid composition in breast fat (adipose) tissue. The study included 241 breast cancer patients with nonmetastatic breast carcinoma and 88 patients with benign breast disease in Tours, central France. Laboratory studies have found that n-3 fatty acids, including alpha-linolenic acid and long-chain n-3 polyunsaturated fatty acids, inhibit mammary tumor growth and metastasis. Previous epidemiological studies have given inconclusive results about the association of dietary n-3 polyunsaturated fatty acids with breast cancer risk, perhaps because of methodological issues common to nutritional epidemiology. In the study, fatty acid composition in breast adipose tissue was used as a biomarker of past consumption of fatty acids by the women. Biopsies of adipose tissue were obtained during breast surgery and individual fatty acids were measured and calculated as a percentage of total fatty acids. Unconditional logistic regression modeling was employed to calculate odds ratio estimates while adjusting for age, menopausal status, height, and body mass index. Inverse associations were found between risk of breast cancer and n-3 fatty acid levels in breast adipose tissue. Women in the highest third of alpha-linolenic acid were found to have an odds ratio (OR) of 0.39 (95% confidence intervals (CI) = 0.19-0.78) compared to women in the lowest tertile (trend p = 0.01). Similarly, for women in the highest tertile of docosahexaenoic acid OR = 0.31 (95% CI = 0.13-0.75) compared to women in the lowest tertile (p = 0.016). For women in the highest tertile of the omega-3/omega-6 fatty acid ratio OR = 0.33 (95% confidence interval = 0.17-0.66) compared to women in the lowest tertile (p = 0.0002). The authors conclude that the data suggest a protective effect of omega-3 fatty acids on breast cancer risk and support the hypothesis that the balance between omega-3 and omega-6 fatty acids plays a role in breast cancer.