Diet and Cancer: How Will We Make Progress?

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Clifford A. Hudis, MD

Despite some limitations—albeit fewer than many other diet intervention trials—the data from the trial provide a good argument for a Mediterranean diet enriched by extra-virgin olive oil.

—Clifford A. Hudis, MD

Not only is breast cancer among the most common cancers in women, but it is also one of the most common causes of premature death. Rates of death from the disease vary widely around the world, reflecting variations in risk, screening, and access to highest quality treatment.

Although female gender and age are the most constant risk factors, they are not modifiable. Among the modifiable risk factors, obesity is now emerging as key. Apart from just breast cancer, obesity is poised to replace tobacco use—because of slow and steady progressive control of the latter—as the leading modifiable risk factor for cancer in the United States and possibly other higher-income countries.

It is difficult to talk about obesity without considering energy balance, including exercise and other activity, as well as dietary composition, the latter relating to both total caloric content and also specific components. At the same time, many “healthier” diets may be so because of many factors, not all of which are understood or studied.

More Than Just a Low-Fat Diet

For example, consider a low-fat diet. If proven healthier for some diseases, we are often forced to at least note that it is generally a lower-calorie diet as well. An earlier randomized study of a very low–fat diet in the adjuvant treatment setting for breast cancer demonstrated this: The low-fat diet was also associated with weight loss.1 Hence, its clinical benefits might be partially attributed to lower calorie consumption and weight loss (as was seen in the study), in addition to the specific benefits of lower fat consumption.

Diet and Breast Cancer

In a recent issue of JAMA Internal Medicine, Toledo and colleagues attempted to study the risk of developing invasive breast cancer among women enrolled in a cardiac diet study2; the study is summarized in this issue of The ASCO Post. The women in the study were not “average” women, in the sense that they had a high cardiovascular risk, and this, in many settings, is associated with both obesity and components of the metabolic syndrome, as well as diabetes and a sedentary lifestyle. Acknowledging that this group was perhaps at higher risk, we should also note that these risk factors are common in the United States and elsewhere, and these patients may be more typical than we wish.

The subjects who enrolled were randomized to follow a Mediterranean diet supplemented with extra-virgin olive oil, one supplemented with mixed nuts, or a control group that was simply advised to reduce their dietary fat consumption. More than 4,000 patients participated, and with nearly 5 years of follow-up, 35 cases of breast cancer were identified. The method of detection (screening as opposed to clinical presentation) is not clear, nor is the staging presented. Nonetheless, these factors should not be different across the three arms.

It is interesting to note that almost all cases (33 of 35) were hormone receptor–positive disease, and about one-third (12 of 35) were HER2-positive disease. For each of these biomarkers, the incidence is normally a bit lower, but this may be a reflection of the age of the patients or other factors. Hormone receptor–positive breast cancer is the most common subtype in high-income countries, and there is a plausible link to the chronic white adipose inflammation that is commonly associated with elevated body mass index.3

In the study, the incidence of breast cancer appears to have been greatest among participants on the control diet, lower with the nut-supplemented Mediterranean diet, and lowest with the extra-virgin olive oil. However, the numbers are small, and only the latter achieved statistical significance vs the control.

Limitations yet a Good Argument

This study has some limitations. The endpoint (breast cancer incidence) was secondary, the overall incidence was low, and standard clinical approaches to ascertainment (mammograms and clinical exams at regular intervals) were not described. It appears that the daily caloric intake for all three diets was initially about the same, but by the end of 3 years, the control group actually seemed to have slightly lower daily kilocalorie intake. Unfortunately, weight and body mass index were not described at the 3-year time point. If they remained stable, this study would gain even more utility, as this would suggest more clearly that a specific diet has an impact.

Despite some limitations—albeit fewer than many other diet intervention trials—the data from the trial provide a good argument for a Mediterranean diet enriched by extra-virgin olive oil. The potential risk reductions for breast cancer represent a bonus, given that it generally tastes great anyway! ■

Disclosure: Dr. Hudis reported no potential conflicts of interest.


1. Chlebowski RT, Blackburn GL, Thomson CA, et al: Dietary fat reduction and breast cancer outcome: Interim efficacy results from the Women’s Intervention Nutrition Study. J Natl Cancer Inst 98:1767-1776, 2006.

2. Toledo E, Salas-Salvado 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 175:1752-1760, 2015.

3. Morris PG, Hudis CA, Giri D, et al: Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prev Res (Phila) 4:1021-1029, 2011.

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Mediterranean Diet Supplemented With Extra-Virgin Olive Oil Reduces Risk for Invasive Breast Cancer

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