Estrogen Levels in Nipple Aspirate Fluid and Serum during a Randomized Soy Trial

Abstract

Background Based on the hypothesized protective effect, we examined the effect of soy foods on estrogens in nipple aspirate fluid (NAF) and serum, possible indicators of breast cancer risk. Methods In a cross-over design, we randomized 96 women who produced ≥10 μL NAF to a high- or low-soy diet for 6-months. During the high-soy diet, participants consumed 2 soy servings of soy milk, tofu, or soy nuts (approximately 50 mg of isoflavones/day); during the low-soy diet, they maintained their usual diet. Six NAF samples were obtained using a FirstCyte© Aspirator. Estradiol (E2) and estrone sulfate (E1S) were assessed in NAF and estrone (E1) in serum only using highly sensitive radioimmunoassays. Mixed-effects regression models accounting for repeated measures and left-censoring limits were applied. Results Mean E2 and E1S were lower during the high-soy than the low-soy diet (113 vs. 313 pg/mL and 46 vs. 68 ng/mL, respectively) without reaching significance (p=0.07); the interaction between group and diet and was not significant. There was no effect of the soy treatment on serum E2 (p=0.76), E1 (p=0.86), or E1S (p=0.56). Within individuals, NAF and serum levels of E2 (rs=0.37; p<0.001) but not E1S (rs=0.004; p=0.97) were correlated. E2 and E1S in NAF and serum were strongly associated (rs=0.78 and rs=0.48; p<0.001). Conclusions Soy foods in amounts consumed by Asians did not significantly modify estrogen levels in NAF and serum. Impact The trend towards lower estrogens in NAF during the high-soy diet counters concerns about adverse effects of soy foods on breast cancer risk.

Methodological considerations in estrogen assays of breast fluid and breast tissue

“…Others who are willing to accept even smaller volumes have obtained sufficient NAF from 96% of subjects [14]. Maskarinec et al [8] considered 10 lL as the minimum for analysis and found that 36% of subjects met this criterion. Loud et al [15] considered 500 lL the minimum volume and found that 24% met this criterion in their population of BRCA1/2 carriers.…”

“…Uptake of sulfated estrogens may also be affected [4,5]. Earlier studies of nipple aspirate fluid indicated that the concentration of estradiol is higher in the breast than in serum, and the coefficients of determination (the percent of the variance in breast fluid or tissue that can be accounted for by variation in serum) were generally less than 0.5 [6][7][8]. Nevertheless, the concentrations remain sufficiently constant over time within individuals to be useful as indicators of exposure of individuals [9].…”

Nipple Aspirate Fluid Hormone Concentrations and Breast Cancer Risk

“…However, the association of serum estradiol with breast cancer risk [3] in postmenopausal women [4–6] and possibly in premenopausal women [7, 8], is relatively weak, perhaps because serum and tissue concentrations of estradiol are poorly correlated [9, 10]. For estradiol, several studies report correlations of 0.37 or less [11–13], although a higher correlation has been reported recently in BRCA1/2 carriers [14]. Overall the results indicate that local formation of estradiol rather than simple diffusion from blood is the primary source of estradiol in the breasts of both pre- and postmenopausal women.…”

Soy Food Intake and Biomarkers of Breast Cancer Risk: Possible Difference in Asian Women?

“…For each BEAN2 participant, four diluted NAF specimens equivalent to 4×10 μL NAF (baseline, month 3 or 6, month 7, and month 10 or 13) were sent to the Reproductive Endocrine Research Laboratory, at which E 2 and E 1 S were assessed using RIAs as described previously (13). …”