Nutritional predictors for cellular nipple aspirate fluid: Nutrition and Breast Health Study

Abstract

The presence of epithelial cells in breast nipple aspirate fluid (NAF), irrespective of abnormality, has been associated with increased risk of breast cancer in previous studies. We sought to investigate whether the presence of epithelial cells in NAF is associated with nutritional parameters among 71 healthy premenopausal women who participated in the Nutrition and Breast Health Study and provided any samples of NAF during the study. Total of 142 samples which were obtained over a 1-year period of intervention with low-fat and/or high vegetable-fruit diets were available for cytological evaluation. The odds ratios (ORs) and 95% confidence intervals (CIs) for the detection of epithelial cells in NAF were estimated by fitting generalized estimating equations models by quartile level of nutritional parameters. The probability of yielding epithelial cell-positive NAF progressively increased with increasing total fat intake (p=0.001). The OR for the highest quartile level of fat intake, compared with lowest, was 7.22 (95% CI 1.14-45.82). On the other hand, there were a marginally significant inverse association with total fiber intake as well as an weak inverse association with the number of servings of fruit and vegetables. Furthermore, the probability of detecting epithelial cells in NAF decreased with increasing plasma levels of lutein and alpha-carotene (p-values for linear trend; 0.001 and 0.049, respectively). The ORs for the highest versus lowest quartile levels are 0.17 (95% CI 0.04-0.65) and 0.19 (95% CI 0.04-0.91), respectively. These results are generally in support of roles of nutritional factors in breast cancer and thus further studies are warranted.

Nutrients and nipple aspirate fluid composition: the breast microenvironment regulates protein expression and cancer aetiology

“…Several prospective or cohort studies have reported an inverse Vitamins [11,25] provitamin A [9] vitamin E [9] retinol [10,11,25] association between breast cancer risk and serum/plasma carotenoids, including a-and b-carotenes and lutein [59,60]. Despite being a relatively minor component among total carotenoids, it is intriguing that lutein showed a significant inverse association [25].…”

“…However, it is also possible that other micronutrients, such as isothiocyanate, lutein and folate (abundantly present in dark-green vegetables), may account for the protective effects in breast tissue [3]. In a study of Kato et al [25], the association with antioxidant vitamin levels was only observed in plasma but not in NAF, undermining the potential effects of these vitamins on breast epithelial cells. However, it is worth noting that levels of a variety of endogenous and exogenous biochemical components in NAF, such as cholesterol, estrogens, and isoflavone, are not correlated with their blood levels [18,45].…”

“…However, it is worth noting that levels of a variety of endogenous and exogenous biochemical components in NAF, such as cholesterol, estrogens, and isoflavone, are not correlated with their blood levels [18,45]. In fact, when correlations between plasma and NAF levels were examined for cholesterol and antioxidant vitamins at baseline, significant correlations were only observed for a-and b-carotenes, and to a lesser extent for lycopene and cryptoxanthin [25]. Carotenoids can also be oxidized in the lipid-rich environment of the breast, as well as lipid oxidation products can be at very high levels in the breast microenvironment [30,31].…”

“…It was also found that concentrations of 5,6-cyclolycopene-1,5-diol, the oxidation product of lycopene, were much higher in NAF than in plasma, and that measurable lycopene levels in some NAF samples were all in the oxidized form [7]. Recently, it was reported that dietary fibre intake may reduce the probability of yielding NAF enriched of epithelial cells, limiting the breast ductal cell proliferation and its turnover [25]. Likewise, an inverse association between dietary fibre intake and BC risk was observed in some cohorts and case-control studies (reviewed in [34]); dietary fibre has been postulated to inhibit intestinal reabsorption of excreted biliary estrogens, limiting the increased stimulation of NAF prolactin and steroids due to increased dietary fat intake [28].…”

“…Oxidative mechanisms may negatively affect the breast cells lining the ducts, making replenishment of antioxidant micronutrients through the diet is a very important factor for maintaining breast tissue physiology and homeostasis. In the Nutrition and Breast Health Study, it was also reported that plasma levels of c-tocopherol (but not b-tocopherol) decreased significantly in low-fat diet habit [25]. Based on the evidence that tocopherol and retinol levels found in NAF were not targeted by any intervention and did not show significant changes [10,11,25], it is possible that the breast tissue stores of tocopherols are less affected by diet than those of plasma.…”