Story behind and scientific rationale for the study

In ancient Greece, olive oil was known as an "elixir of youth and health"; Hippocrates referred to it as “the great healer” whilst the poet Homer called olive oil “liquid gold”. Centuries later, research offers evidence about the benefits of incorporating olive oil in our daily diets including potential cardioprotective, chemopreventive and neuroprotective effects. In 2015, a secondary analysis of the PREDIMED trial, although based on few incident cases, showed women randomized to a Mediterranean diet supplemented with a free provision of extra virgin olive oil (EVOO) had a remarkably 62% lower risk of invasive breast cancer compared to those randomized to a low-fat control diet. This trial provided first-level scientific evidence on breast cancer protective properties of EVOO within the context of the Mediterranean diet. Nonetheless, based on observational studies, the association between olive oil and breast cancer is unclear. A recent systematic review pooled the results of 14 studies and reported an inverse association between olive oil consumption and breast cancer risk, although the association was reproducible in case-control studies but not in cohort studies. Because no large prospective studies examined the association between total olive oil consumption and invasive breast cancer risk in the U.S. population where the average consumption of olive oil is low compared with Mediterranean populations, we aimed to longitudinally examined the association between olive oil consumption and breast cancer risk among women in the Nurses’ Health Studies.

 How did we approach the question?

We used health data collected between 1990 and 2018 for 71,330 women participating in the Nurses’ Health Study (NHS) and 93,295 women in the Nurses’ Health Study II (NHSII). Information on reproductive history, lifestyle, and other potential risk factors were collected every two years throughout follow-up through self-administered questionnaires. All participants were free of cancer at the beginning of the study and completed dietary questionnaires every four years. During the study period, 9,638 incident invasive breast cancer cases were reported. Breast cancer cases were identified from biennial questionnaires and confirmed by medical record review.

Total olive oil intake was calculated from the sum of 3 questionnaire questions related to olive oil intake:

• olive oil salad dressing
• olive oil added to food or bread
• olive oil used for baking and frying at home.

Olive oil intake was categorized according to frequency of consumption. We also analyzed olive oil intake as a continuous variable, converting intake to grams (one tablespoon is equivalent to 13.5g of olive oil). To better represent long-term exposures and reduce within-person variation, cumulative averages of total olive oil intake were computed from all previous questionnaires up to the start of each two-year follow-up interval.

We used time-varying Cox proportional hazard models to calculate multivariable-adjusted hazard ratios and 95% confidence intervals according to categories of cumulative average of olive oil intake. All analyses were stratified by cohort and calendar year, and age in months was the underlying time scale, enabling the finest possible control for confounding by age and secular trends. In the multivariable-adjusted model, we included a priori selected confounders: race/ethnicity, Mediterranean or Southern European ancestry, socioeconomic status, age at menarche, oral contraceptive use, parity, age at first birth, breastfeeding history, menopausal status and postmenopausal hormone use, age at menopause, family history of breast cancer, history of benign breast disease, height, BMI at age 18, total caloric intake, diet quality, physical activity, alcohol intake and weight change from age 18 years.

 What did we find?

Total olive oil intake was not associated with invasive breast cancer risk either when we used the cumulative average intake or when we used an average of the last two most recent measurements. There was no association between olive oil and the risk of ER-negative or positive tumors, or tumor molecular subtypes (luminal A, luminal B, basal-like or HER2-enriched) when comparing extreme categories of consumption. Stratified analysis showed no significant effect modification by menopausal status, ancestry, current BMI, or diet quality.

 Putting our findings in context

Our results align with meta-analyses of prospective studies, which generally show that consuming olive oil is not related to breast cancer risk. Of note, our analysis focused on a non-European population where olive oil intake is relatively low. Therefore, our results may not be generalizable. We evaluated “olive oil” which certainly could be a blend of refined and virgin olive oils or virgin olive oils that preserve their minor compounds. Unfortunately, we could not distinguish between olive oil varieties containing different amounts of polyphenols and other nonlipid bioactive compounds. This fact may explain our null results, and further studies are needed to answer this question. Nonetheless, we previously found significant inverse associations between olive oil intake and total cardiovascular disease and coronary heart disease  and premature death in these U.S. cohorts, which could be possibly attributed to the lipid profile (high in MUFA, especially oleic acid) rather than the bioactive minor compounds.

 Take-home message

While the findings were null, this is the largest study of its kind highlighting that olive oil consumption at relatively low intake levels is not associated with breast cancer risk. Consumers receive many negative messages about what not to eat, thus this study importantly features a source of healthy fats. Consumption of a Mediterranean diet, which is based on plant-based foods, fish and extra virgin olive oil, is known to reduce the risk of several chronic diseases and is safe. Some components of this dietary pattern may also prevent breast cancer, although further research is necessary to understand the impact of olive oil specifically.