Studies have suggested that plant flavonoids have many biological benefits, such as the antioxidant, anti-inflammatory, anti-tumor 
and anti-atherosclerosis effects 
. Cancer preventive phytochemicals, especially flavonoids, have been shown to suppress or block cancer progression by a variety of mechanisms 
. More attention is given to preventing colon, rectum, lung, prostate or breast cancer through daily diet because of the chemoprotective effects of dietary flavonoids and other phytochemicals. However, most of the cancer preventive effects of phytochemicals, including flavonoids, were shown in animal and cell culture studies; human clinical trials examining the chemopreventive potential of phytochemicals are lacking. In fact, some epidemiologic studies assessing the association between the flavonoid intake and the breast cancer risk have yielded inconsistent results. Moreover, different dietary flavonoid subclasses, which vary in chemical structures and bioactivities, may have different chemopreventive effects on breast cancer. The present meta-analysis of population studies supports a significant association of flavonols and flavones intake with a reduced risk of breast cancer. However, neither the total flavonoids nor the other flavonoid subclasses intake has been found to be associated with the breast cancer risk. More studies are warranted to confirm the results. The findings likely provide useful insight and evidence that can be used by registered dietitians and other healthcare professionals when discussing diet and cancer prevention with patients.
In establishing flavonoids as one of the contributors to the protective effects, the very first step is to estimate flavonoid intake from various dietary sources 
. Yet dietary flavonoids are composed of a great variety of polyphenolic compounds which widely exist in plant foods, so it is difficult to assess the intake of total flavonoids and flavonoid subclasses. Part of the inconsistencies of epidemiological studies may be attributable to the difficulty in measuring intake levels of flavonoids. The estimated daily intake of total flavonoids in the same country may differ in different studies, suggesting that some heterogeneity may exist in dietary assessment of flavonoids intake. Estimation of flavonoid intake from dietary sources has been feasible since 2003 when the U.S. Department of Agriculture (USDA) released the database for the flavonoid content of selected foods. Since then, many articles have been published in which flavonoid intake in various subpopulation groups was estimated from relatively large, current databases of flavonoid concentration data. Furthermore, biomarkers such as urinary excretion or plasma metabolite levels could complement dietary assessment of the bioavailability of these dietary compounds. However, information is still limited on the intake of flavonoids and each flavonoid subclass in the United States and worldwide. More carefully designed studies should be performed to improve the method and database for assessing dietary flavonoids intake.
Menopausal status and estrogen-receptor (ER) status, as effect modifiers, may greatly effect the association between the flavonoid intake and breast cancer risk. Some studies showed that the association between the intake of soy isoflavone and the reduced risk of breast cancer incidence or recurrence was stronger in post-menopausal women than in premenopausal women 
. Although the other flavonoid subclasses have weaker phytoestrogen activity than isoflavones, the menopausal status and ER status also influence their association with breast cancer. The present analysis indicates a significant association of flavonol, flavone and flavan-3-ol intake with the reduced risk of breast cancer in post-menopausal but not in pre-menopausal women. The possible mechanism might partially lie in that flavonoids affect the ovarian synthesis of sex hormones or the alteration of other menstrual cycle characteristics 
. Although flaonoids, especially isoflavones, are most widely recognized for their weak estrogenic activity, they have a variety of other biologic activities that may influence cancer risk, such as antioxidant, antiproliferative, 
and antiangiogenic activities 
as well as inhibiting the effects of cytokines, growth factors, and several enzymes 
. The anticancer effects of flavonoids may be exerted by the combination of a variety of biologic activities, and would be influenced by some established risk factors for cancer such as alcohol consumption 
, smoking status, energy intake, menopausal status, use of hormonal treatment for menopause et al 
. Therefore, the chemoprevention of flavonoids may be varied among different subpopulation. More carefully designed studies should be performed to investigate the association of phytochemicals with cancer.
The present study suggests the intakes of flavonols and flavones, but not the other flavonoid subclasses or total flavonoids, can potentially contribute to breast cancer prevention, especially among post-menopausal women. More studies are needed to confirm the findings.