November 4, 2015

Mediterranean Diet, Extra-virgin Olive Oil, and Breast Cancer Risk

Is there a connection between EVOO and lower incidence of breast cancer?
The PREDIMED data have yielded more fascinating insights about the health benefits of the Mediterranean diet—this time as it affects the incidence of breast cancer in women who had not previously had the disease. Consider these findings if you need another reason to recommend this healthy diet to patients.


Toledo E, Salas-Salvadó J, Donat-Vargas C, et al. Mediterranean diet and invasive breast cancer risk among women at high cardiovascular risk in the PREDIMED trial: a randomized clinical trial. JAMA Intern Med. 2015 Sep 14:1-9. [Epub ahead of print]


The PREDIMED study was a randomized, single-blind, controlled field trial conducted at primary healthcare centers in Spain. 


From 2003 to 2009, 4,282 women aged 60 to 80 years were enrolled. At enrollment, they were free of cardiovascular disease but might have had either type 2 diabetes mellitus or at least 3 of the following major cardiovascular risk factors: smoking, hypertension, elevated low-density lipoprotein cholesterol level, low high-density lipoprotein cholesterol level, overweight or obesity, or family history of premature coronary heart disease.
The women were an average age of 67.7 years old and had an average body mass index of 30.4. Most of them had undergone menopause before the age of 55, and less than 3% used hormone therapy. 

Study Medication and Dosage

Participants were randomly allocated to 1 of 3 diets: a Mediterranean diet supplemented with extra-virgin olive oil (EVOO), a Mediterranean diet supplemented with mixed nuts, or a control diet. The control group (n=1,391) was advised to consume a reduced-fat diet. Participants in the 2 intervention groups were given supplementary foods for free: EVOO (n=1,476; 1 L/wk for the participant and their families) or mixed nuts (n=1,285; 30 g/d: 15 g walnuts, 7.5 g hazelnuts, and 7.5 g almonds) according to their randomization group. 

Outcome Measures

The primary outcome tracked in the trial was incidence of cardiovascular events. Breast cancer incidence was a secondary outcome measure of the trial for women without a prior history of breast cancer (n=4,152). Cases were defined as the first invasive breast cancer that was confirmed by cytological or histological examination. Medical records were reviewed to extract these data, and cases were identified through December 1, 2010.

Key Findings

After a median follow-up of 4.8 years, 35 confirmed incident cases of breast cancer were identified. Observed rates (per 1000 person-years) were 1.1 for the Mediterranean-diet-with-EVOO group, 1.8 for the Mediterranean-diet-with-nuts group, and 2.9 for the control group. The multivariable-adjusted hazard ratios (HRs) vs the control group were 0.32 (95% confidence interval [CI]:0.13-0.79) for the group consuming a Mediterranean diet with EVOO and 0.59 (95% CI:0.26-1.35) for the group consuming a Mediterranean diet with nuts. In analyses with yearly cumulative updated dietary exposures, there was a 28% risk reduction for each additional 5% of calories from EVOO (HR:0.72; 95% CI:0.57-0.90).

Practice Implications

We have long had good reason to encourage women to consume a Mediterranean style diet as it may lower breast cancer risk. We now have good reason to put greater emphasis on encouraging consumption of EVOO. 
According to this new analysis of data from the PREDIMED (Prevención con Dieta Mediterránea) cohort, women eating a Mediterranean diet supplemented with EVOO showed a 68% (HR:0.32) relatively lower risk of malignant breast cancer than those allocated to the control diet. Women eating a Mediterranean diet supplemented with nuts showed a nonsignificant risk reduction compared with women in the control group. Keep in mind that those participants in this trial were for the most part following a Mediterranean diet despite their allocation to a low-fat diet. The study participants changed their diets only slightly, even with quarterly counseling sessions and encouragement from dieticians. Over the nearly 5 years of the trial, the only significant changes made by the 2 Mediterranean diet groups were in fish and legume consumption; fish consumption increased by 0.3 servings per week and legumes by 0.4 servings per week in comparison to the control group. No other changes reached statistical significance, except for EVOO or nut consumption.
The findings of this most recent report from the PREDIMED trial give further support to the idea that the Mediterranean diet is protective against breast cancer…
The PREDIMED study has been reviewed previously in this journal, including in our special issue on cardiology. There is an important distinction to note about the “low-fat control diet.” Although the control group was counseled to follow a low-fat diet, they were hardly compliant. The percentage of total energy calculated in the diet from fat dropped from 39% to 37%, a nonsignificant decrease of 1.96%, over the course of the trial.1 No conclusions can be drawn about the impact of switching to a low-fat diet from the initial study’s data analysis, as no one appears to have really done so. One year into the study, nearly 92% of the low fat diet control group reported that olive oil was the primary culinary fat in their diets. At 5 years, this consumption level had increased to more than 96%. More than 58% of the control group on the low-fat diet reported consuming more than 4 T of olive oil per day. It almost seems as if this low-fat group had figured out that they were the controls and were doing their best to mimic the experimental diet.
It is difficult to determine whether the benefits are attributed only to the EVOO consumption or to the Mediterranean diet. In past reviews of data from this cohort, the diet actually consumed by the low-fat control group did not differ greatly from those assigned to the Mediterranean diet, so it would not be unreasonable to assume that the EVOO in conjunction with a Mediterranean diet was responsible for the benefits observed.
There have been several large case control studies published in the last few years that also suggest benefit from the Mediterranean diet in reducing breast cancer incidence.
A 2014 Greek study reported that in comparing 250 newly diagnosed breast cancer patients (in participants aged 56 y±12 y) with 250 age-matched controls, 1 unit greater adherence to the Mediterranean diet was associated with 9% lower likelihood of having breast cancer (odds ratio [OR]=0.91; 95% CI:0.86-0.97). Their data suggested the most important components with beneficial effect were nonrefined cereals, vegetables, fruits, and alcohol, followed by an unfavorable effect of red meat. Adherence was evaluated using the 11-component MedDietScore (theoretical range 0-55).2
A Spanish study published in September 2014 compared 1,017 breast cancer cases and 1,017 matched controls to examine the association between dietary patterns and breast cancer in general; menopausal status and tumor subtypes were also factored in.3 Women adhering to a Western diet had a 46% higher overall risk of breast cancer (top vs the bottom quartile, OR:1.46; 95% CI:1.06-2.01). This risk was even higher, 75%, in premenopausal women adhering to a Western diet (OR:1.75; 95% CI:1.14-2.67). On the contrary, following a Mediterranean diet was associated with a 44% lower risk of developing breast cancer (top quartile vs the bottom quartile, OR:0.56; 95% CI:0.40-0.79). The protective effect of a Mediterranean-pattern diet was even stronger for triple-negative tumors (OR:0.32; 95% CI:0.15-0.66; P=0.04). 
A year earlier, data from a large cohort appeared in an article in the International Journal of Cancer. Mediterranean diet adherence and breast cancer risk was calculated from 335,062 women recruited between 1992 and 2000 in 10 European countries and followed for an average of 11 years. Diet adherence was estimated through an adapted relative Mediterranean diet (arMED) score that excluded alcohol. A total of 9,009 postmenopausal and 1,216 breast cancer patients were identified among the cohort. The arMED was inversely associated with the risk of breast cancer overall and in postmenopausal women (HR:0.94; 95% CI:0.88-1.00; P for the trend=0.048 and HR:0.93; 95% CI:0.87-0.99; P for the trend=0.037, respectively). The association was more pronounced in estrogen receptor/progesterone receptor tumors (HR:0.80; 95% CI:0.65-0.99; P for the trend=0.043). The arMED score was not associated with breast cancer in premenopausal women.4
It is interesting to note that a study analyzing data on Swedish women published in 2013 failed to find a similar association. The Swedish Women’s Lifestyle and Health cohort study included 49,258 women aged 30 to 49 years at recruitment between 1991 and 1992. During that period, 1,278 incident breast cancers were diagnosed. Adherence to a Mediterranean dietary pattern was not statistically significantly associated with reduced risk of breast cancer overall or with specific breast tumor characteristics.5 The women in this cohort were younger and likely to have been premenopausal, so these findings are similar to the findings of the previous study mentioned. It may be that the Mediterranean diet has greater impact on older menopausal woman. (I have a theory that the Mediterranean diet is made more effective with sun exposure; if this is true, then benefits may vary by latitude.)
The findings of this most recent report from the PREDIMED trial give further support to the idea that the Mediterranean diet is protective against breast cancer and that EVOO in particular may offer even greater benefit.

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  1. Estruch R, Ros E, Salas-Salvadó J, et al; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368(14):1279-1290.
  2. Mourouti N, Kontogianni MD, Papavagelis C, et al. Adherence to the Mediterranean diet is associated with lower likelihood of breast cancer: a case-control study. Nutr Cancer. 2014;66(5):810-817. 
  3. Castelló A, Pollán M, Buijsse B, et al. Spanish Mediterranean diet and other dietary patterns and breast cancer risk: case-control EpiGEICAM study. Br J Cancer. 2014;111(7):1454-1462. 
  4. Buckland G, Travier N, Cottet V, et al. Adherence to the Mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study. Int J Cancer. 2013;132(12):2918-2927. 
  5. Couto E, Sandin S, Löf M, Ursin G, Adami HO, Weiderpass E. Mediterranean dietary pattern and risk of breast cancer. PLoS One. 2013;8(2):e55374.