Mediterranean Diet and Breast Cancer

From Medscape Education Clinical Briefs
Can a Mediterranean Diet Avert Breast Cancer?

News Author: Nick Mulcahy
CME Author: Laurie Barclay, MD




Clinical Context

Since 2008, the global incidence of breast cancer has risen by more than 20%, and it is the leading cause of cancer in women. Although findings from some observational studies suggest that the Mediterranean diet (MeDiet) may lower breast cancer risk, there have been no previous findings from randomized trials.

The goal of this secondary analysis of the randomized PREDIMED (Prevención con Dieta Mediterránea) trial by Martínez-González and colleagues was to compare the impact of 2 interventions of the MeDiet vs advice to follow a low-fat diet (control) on breast cancer incidence. Original findings from the PREDIMED trial showed that following the MeDiet -- which features vegetables, fruits, fish, and olive oil -- was associated with a lower risk for cardiovascular disease.


Study Synopsis and Perspective

The MeDiet appears to protect against more than just cardiovascular disease -- it might also prevent breast cancer, according to results from the randomized controlled PREDIMED trial.

The diet is characterized by an abundance of plant foods, fish, and olive oil and has been repeatedly shown to be cardioprotective in major clinical trials.

The PREDIMED study, conducted from 2003 to 2009, is one of those trials. It was stopped early because of the cardiovascular benefit seen with a MeDiet, compared with a low-fat diet.

The researchers now report on breast cancer incidence -- a secondary outcome. And the news is promising.

"The results of the PREDIMED trial suggest a beneficial effect of a MeDiet supplemented with extra-virgin olive oil in the primary prevention of breast cancer," write the study authors, led by Miguel A. Martínez-González, MD, from the Instituto de Salud Carlos III in Madrid, Spain.

Importantly, this randomized trial is the first to see the effect of a long-term dietary intervention on breast cancer incidence.

Of the 4282 postmenopausal women involved in the 3-group trial, there were 35 confirmed incident cases of breast cancer. Median follow-up was 4.8 years.

The observed rates for breast cancer (per 1000 person-years) were 1.1 for those assigned to the MeDiet supplemented with extra-virgin olive oil, 1.8 for those assigned to the MeDiet supplemented with nuts, and 2.9 for those assigned a low-fat diet.

The risk for malignant breast cancer was 62% lower in women randomly assigned to the MeDiet supplemented with extra-virgin olive oil than in those randomly assigned to the low-fat diet (hazard ratio, 0.38; P = .02).

The MeDiet supplemented with nuts was also associated with a lower risk, but it was not statistically significant.

"The number of observed cases of breast cancer is small, but the results are statistically significant," summarized Dr Martínez-González in an interview with Medscape Medical News.

This nutritional intervention study is the first to evaluate the effect of the MeDiet on breast cancer, say the researchers.

The study findings were published online September 14 in JAMA Internal Medicine.

Mitchell H. Katz, MD, one of the journal's editors, reports that the study design caught their eye. "We were immediately impressed that it was a randomized clinical trial of diet," he writes in an accompanying editorial.

The study has a "high-quality structure," according to Dr Katz, who is director of the Los Angeles County Department of Health Services, Los Angeles, California.

Dr Katz and the PREDIMED team acknowledge that the study has multiple limitations. For example, the women were not all screened for breast cancer with mammography, and they were all white and postmenopausal. Furthermore, to be enrolled in the trial, the women had to be at high risk for cardiovascular disease.

The researchers caution that longer-term, larger trials with more cases of breast cancer are needed. However, this will be a tall order, given the associated time and expense, Dr Martínez-González explained.

In the meantime, he is advising his female patients that a MeDiet might be protective against invasive breast cancer.


More Study Details

Dieticians ran individual and group lessons on the MeDiet for study participants.

The women in the 2 MeDiet groups were given supplementary foods for free: either extra-virgin olive oil (1 L/week for the participant and her family) or mixed nuts (walnuts 15 g, hazelnuts 7.5 g, and almonds 7.5 g), depending on their assigned diet.

Initially, funding for the supplements came from the Instituto de Salud Carlos III, which is the equivalent of the National Institutes of Health. "At first, we went to the supermarket for supplies," said Dr Martínez-González.

But across time, the organizers received bulk shipments of products donated by olive oil producers in Spain and nut producers in California and Spain.

The supplements were supplied to participants to ensure a high consumption of the key components of a traditional MeDiet and to promote a better overall adherence to the intervention.

Participants completed questionnaires annually to provide information on adherence to diet, food intake, and lifestyle in general.

Other prospective cohort studies have evaluated the association between adherence to a MeDiet and breast cancer risk, but none have been randomized controlled trials, the researchers report.

Furthermore, a meta-analysis of case-control studies concluded that the consumption of olive oil, including extra-virgin and other common types, was inversely associated with breast cancer incidence (Lipids Health Dis. 2011;10:127).

However, at least 1 major study, the European Prospective Investigation Into Cancer and Nutrition study, did not find any such association (Int J Cancer. 2012;131:2465-2469).

The PREDIMED researchers explain that all types of olive oil provide a high supply of monounsaturated fatty acids, mainly oleic acid, as well as squalene. Extra virgin, which is a thinner, more viscous oil, also contains various biologically active compounds, such as the polyphenols oleocanthal, oleuropein, hydroxytyrosol, and lignans.

"In vitro studies have suggested that oleic acid has an antiproliferative effect by affecting the expression of human oncogenes," they write.

The potential beneficial effect of the MeDiet is likely explained by several mechanisms, including a reduction in DNA oxidative damage, the team says.

The PREDIMED trial was supported by Instituto de Salud Carlos III, the US National Institutes of Health, and other agencies. The supplemental foods were donated by Patrimonio Comunal Olivarero and Hojiblanca (olive oil), the California Walnut Commission (walnuts), Borges SA (almonds), and La Morella Nuts (hazelnuts). Some of the study authors have disclosed relevant financial relationships with the food industry, including the International Nut and Dried Fruit Foundation and the California Walnut Commission, and with pharmaceutical companies. Dr Katz has disclosed no relevant financial relationships.

JAMA Intern Med. Published online September 14, 2015.


Study Highlights

At primary healthcare centers in Spain from 2003 to 2009, a total of 4282 women 60 to 80 years old and at high risk for cardiovascular disease were invited by their primary care clinicians to participate in the single-blind PREDIMED trial.
Participants were randomly assigned 1:1:1 to receive a MeDiet supplemented with extra-virgin olive oil, a MeDiet supplemented with mixed nuts, or counseling on how to reduce dietary fat (control group).
Participants in the extra-virgin olive oil group received 1 L/week of oil to use for themselves and their families at no charge. Those in the mixed nuts group received 30 g/day of nuts, consisting of 15 g of walnuts, 7.5 g of hazelnuts, and 7.5 g of almonds.
For the 4152 women without a previous history of breast cancer, a prespecified secondary outcome was breast cancer incidence.
There were 35 confirmed incident cases of breast cancer during follow-up (median duration, 4.8 years).
Per 1000 person-years, there were 1.1 cases of breast cancer for the MeDiet with extra-virgin olive oil group, 1.8 for the MeDiet with nuts group, and 2.9 for the control group.
Compared with the control group, the MeDiet with extra-virgin olive oil group had a 68% reduction in breast cancer incidence (multivariable adjusted hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.13-0.79; P =.02).
For the MeDiet with nuts group, the HR was 0.59 (95% CI, 0.26-1.35), but this result was not statistically significant.
For each additional 5% of calories from extra-virgin olive oil, the HR for breast cancer was 0.72 (95% CI, 0.57-0.90), based on analyses with yearly cumulative updated dietary exposures.
On the basis of their findings, the investigators concluded that this randomized trial was the first to show an effect of a long-term dietary intervention on breast cancer incidence.
The findings suggest that a MeDiet supplemented with extra-virgin olive oil is beneficial in the primary prevention of breast cancer.
However, the investigators caution that their results need to be confirmed in longer-term and larger studies, because this study was a secondary analysis of a previous trial and there were few incident breast cancer cases.
Study limitations include failure to screen all women for breast cancer with mammography before study entry, and limited generalizability because participants were white, postmenopausal, and at high risk for cardiovascular disease.
In light of the long duration and high costs of longer-term, larger randomized trials, while awaiting confirmation, clinicians may wish to advise their female patients that a MeDiet may help protect against breast cancer.
Mechanisms underlying the potential benefit of the MeDiet may include a reduction in DNA oxidative damage.
Oleic acid contained in olive oil may affect the expression of human oncogenes to inhibit cancer cell growth and reproduction.

Clinical Implications

Findings from this secondary analysis of a previous trial suggest that a MeDiet supplemented with extra-virgin olive oil is beneficial in the primary prevention of breast cancer.
The results of this secondary analysis need to be confirmed in longer-term and larger studies. However, while awaiting these results, clinicians may wish to advise their female patients that a MeDiet may help protect against breast cancer.
Implications for the Healthcare Team: Members of the healthcare team should be aware that this evidence from randomized trial findings is the first to show an effect of a long-term dietary intervention on breast cancer incidence.