Adherence to a Mediterranean dietary pattern was not associated with reduced risk of breast cancer overall, nor of specific breast tumor characteristics, overall, or in premenopausal and postmenopausal participants. Previous studies investigating the possible association between a Mediterranean diet and breast cancer risk have reported conflicting results. While some studies found no association of this diet with the risk of breast cancer overall 
, in premenopausal 
, or in postmenopausal women 
, a protective association in postmenopausal women 
, Hispanic postmenopausal women 
, and Asian American postmenopausal women 
has been described. Indeed, studies that found a protective association of a Mediterranean diet with breast cancer risk have reported this association in postmenopausal women only 
. While WLH study participants may have reached menopause during follow-up, they are somewhat younger (30 to 49 years in 1991–1992) than populations in many other studies, and it is possible that results may differ in older women.
The Greek EPIC cohort found a reduction in total mortality with closer adherence to a Mediterranean diet, and reported that moderate alcohol consumption was one of the components with greater contribution to this association 
. Moderate alcohol consumption, which is a risk factor for breast cancer 
, increased our score, contrary to lower or higher consumption. However, when we excluded alcohol consumption from the score, no statistically significant association was found. One published study treated alcohol as a negative factor, (giving a value of 1 to consumptions above the median, and a value of 0 otherwise), and found a protective association 
Risk factors for breast cancer might differ by hormone receptor status 
. Previous studies have examined whether a Mediterranean diet has a different influence on the risk of ER- and PR-negative and positive breast cancer, and have reported conflicting results 
. The Nurses Health Study cohort found no association with ER-positive breast cancer risk, and an inverse association with ER-negative breast cancer 
. However, data from the French EPIC cohort showed no association of a Mediterranean diet with ER-negative breast cancer, and a protective association with ER-positive/PR-negative tumors 
. We found no association between adherence to a Mediterranean dietary pattern and the risk of ER- or PR-negative cancer. When we examined ER and PR receptor statuses jointly, we found an increased risk of ER-negative/PR-negative tumors both overall and in premenopausal women. However, these results might be due to chance, and were not statistically significant when we excluded alcohol from the Mediterranean diet score. We also examined the possible association between adherence to a Mediterranean dietary pattern and risk of ER-negative/PR-negative tumors among non-alcohol drinkers, and found no association overall, in premenopausal, or in postmenopausal participants.
Previous studies have used different methods to ascertain adherence to a Mediterranean diet. Most of them used pattern identification methods to define a specific dietary pattern 
. A limitation of this method is that the identified pattern is population-dependent, and may not apply to other populations. Other studies have used a method similar to ours, constructing a score assuming an a priori
knowledge of the composition of the Mediterranean diet 
. Both methods ascertain dietary patterns, which measure the complexity of diet more accurately than simply considering individual food items 
. A limitation of the Mediterranean diet score is that the composition of a specific component might vary from one population to another. For example, in Mediterranean countries olive oil is the main source of unsaturated fat, unlike in non-Mediterranean countries. However, the ratio of unsaturated to saturated fat used in the present report accommodates the low consumption of olive oil-derived monounsaturated lipids in non-Mediterranean countries. Differences in the methods used to ascertain Mediterranean diet may explain the discrepancies in the results of published studies.
The strengths of the WLH study are its prospective design, and extensive information on potential confounders. Furthermore, the use of national registries to identify disease outcome allowed for an almost complete follow-up. Diet was measured using a validated food frequency questionnaire 
, and it has been shown that these questionnaires provide valid estimates of diet measured by the Mediterranean diet score 
. However, when diet is assessed through food frequency questionnaires, measurement error is often substantial, which could bias risk estimates toward the null 
. The effect of measurement error is expected to increase with increasing number of measured dietary exposures 
. This is particularly relevant in the current investigation, as several dietary factors make up the exposure of interest (Mediterranean diet score components), and are also used as adjusting covariates.
Furthermore, our results may be explained to a certain extent by residual confounding. Indeed, we found that women who adhered more closely to a Mediterranean dietary pattern were more likely to have a family history of breast cancer, to use oral contraceptives and hormone therapy, and to have a higher alcohol consumption, all of which are risk factors for breast cancer. Another concern is the single measurement of diet at baseline and the interval between diet ascertainment and breast cancer outcome. This, however, is likely to create non-differential misclassification, and would attenuate any true association.
The diet of WLH study participants is different from that of participants in studies conducted in Mediterranean countries. For example, the consumption of vegetables and fruits in this cohort was lower than in the Greek EPIC cohort, which also examined the association between Mediterranean diet and breast cancer risk 
. While the Greek study did not report strong evidence for a beneficial effect of a Mediterranean diet on breast cancer risk (RRs were 0.88, 95% CI: 0.75–1.03; 1.01, 95% CI: 0.80–1.28; and 0.78, 95% CI: 0.62–0.98) overall, in premenopausal and postmenopausal women, respectively), it is possible that there is a consumption threshold above which beneficial components act, and that this threshold was not reached in the WLH cohort. We used a score that measured consumption patterns of different Mediterranean diet components (high or low in our study population), which should accommodate the consumption of components that might be different from other studies. However, while the consumption of more beneficial components such as vegetables and fruits was lower in the WLH cohort, the low to moderate alcohol consumption was similar to the moderate alcohol consumption in Mediterranean countries. It is therefore possible that the contribution of alcohol in higher Mediterranean diet scores was stronger in this cohort compared to studies conducted in Mediterranean countries. Our results showed a statistically significant increase in breast cancer risk in premenopausal women that was particularly strong in women with a Mediterranean diet score of 8 or 9. In our data, women with highest Mediterranean scores had the highest alcohol consumption. The increased risk might be due to residual confounding by alcohol consumption, or chance. When excluding alcohol from the Mediterranean diet score and controlled for alcohol consumption in the statistical model, the increased breast cancer risk associated with Mediterranean diet scores of 8 or 9 in premenopausal women remained.
To our knowledge, this is the first Scandinavian study that investigates the possible association between adherence to a Mediterranean dietary pattern and breast cancer risk, and no reduction in breast cancer risk was found. This was true regardless of participant characteristics, and for all breast tumor characteristics examined.