Study Results Suggest That Flavones and Flavan-3-ols Protect against Breast Cancer

Summary

Consumption of fruits, vegetables, and carotenoids has been shown to reduce the risk of breast cancer, as they are rich in flavonoids. The objective of the Cancer Prevention Study II [CPS-II] Nutrition Cohort was to evaluate the association of several flavonoids on the risk of invasive breast cancer in women stratified by estrogen-negative status, as discussed in this article.

  • breast cancer
  • nutrition physiology
  • nutrition clinical trials

Consumption of fruits, vegetables, and carotenoids has been shown to reduce the risk of breast cancer, in particular estrogen-negative (ER–) breast cancer [Jung S et al. J Natl Cancer Inst 2013; Aune D et al. Breast Cancer Res Treat 2012; Eliassen AH et al. J Natl Cancer Inst 2012; Zhang X et al. Am J Clin Nutr 2012]. Fruits and vegetables are rich in flavonoids, which are potential anticancer agents. Flavonoids have antioxidant, anti-inflammatory anti-proliferative, and pro-apoptotic effects. A recent meta-analysis reported that flavonols and flavones, but not other flavonoid subclasses, were associated with a decreased risk of breast cancer, especially in postmenopausal women [Chang H et al. PloS ONE 2013].

Most previous studies have focused on the association between 1 or 2 subclasses of flavonoids, and no studies have investigated proanthocyanidins. Furthermore, only 3 studies have stratified subjects by the ER status of the breast cancer. The objective of the Cancer Prevention Study II [CPS-II] Nutrition Cohort, presented by Ying Wang, PhD, Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA, was to evaluate the association of several flavonoids on the risk of invasive breast cancer in women stratified by ER status.

The study population included 73,640 women who returned a modified Willett food frequency questionnaire. A total of 56,630 postmenopausal women were included in the analysis after 1752 were lost to follow-up. Women previously diagnosed with cancer and those women who reported energy intake that was outside the acceptable range were excluded from the analysis. The women were followed until they developed breast cancer, they died, the last survey was returned, or June 30, 2009.

At a mean follow-up of 8.5 years, 2116 cases of invasive breast cancer, including 1498 ER+ and 218 ER– cancers, were diagnosed. Flavonoid exposure was assessed with the food frequency questionnaire; information from the USDA flavonoid, proanthocynanidin, and isoflavone databases; and scientific publications. The flavonoids assessed included flavones, flavonols, flavanones, anthocyanidins, flavan3ols, isoflavones, and proanthocyanidins. The women were categorized into quintiles of flavonoid intake. The median intake and range (mg/day) of total flavonoids for each quintile (Q) were Q1 = 9.5 (≤ 118.7); Q2 = 143.7 (> 118.7 to 171.0); Q3 = 201.4 (> 171.0 to 239.2); Q4 = 288.6 (> 239.2 to 363.8); and Q5 = 522.9 (> 363.8 to 2062.8). The mean age ranged from 68.4 to 68.9 years in each quintile, and ∼ 98% of the women in each quintile were white.

The intake of flavones, but not other flavonoids, was inversely associated with total invasive breast cancer risk when evaluated by quintiles (p value for trend = .04) and continuous exposure (RR, 0.96; 95% CI, 0.92 to 1.00). When evaluated by quintiles, intake of no flavonoids was associated with ER+ or ER– breast cancer risk. When evaluated by continuous exposure, flavones intake was inversely associated with ER+ breast cancer risk (RR, 0.96; 95% CI, 0.91 to 1.00), and flavan-3–ol intake was inversely associated with ER– breast cancer risk (RR, 0.81; 95% CI, 0.67 to 0.97; Figure 1).

Figure 1.

Flavonoid Association With Breast Cancer Risk by ER Status

ER=estrogen receptor; SD=standard deviation.The increments are 220 mg/d for total flavonoids, 10 mg/d for anthocyanidins, 40 mg/d for flavan-3–ols, 20 mg/d for flavanones, 1 mg/d for flavones, 10 mg/d for flavonols, 3 mg/d for isoflavones, and 170 mg/d for proanthocyanidins.Reproduced with permission from Y Wang, PhD.

Dr. Wang concluded that these findings are consistent with the results of other research. The results suggest that plant-based diets have a protective role against breast cancer. Future pooled analyses of large cohort studies are warranted to confirm these findings.

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