Estrogen levels in nipple aspirate fluid and serum during a randomized soy trial

On the basis of 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.

In a crossover design, we randomized 96 women who produced 10 microL or more 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 (∼50 mg of isoflavones per day); during the low-soy diet, they maintained their usual diet. Six NAF samples were obtained using a FirstCyte aspirator. Estradiol (E(2)) and estrone sulfate (E(1)S) were assessed in NAF and estrone (E(1)) in serum only, using highly sensitive radioimmunoassays. Mixed-effects regression models accounting for repeated measures and left-censoring limits were applied.

Mean E(2) and E(1)S 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 was not significant. There was no effect of the soy treatment on serum levels of E(2) (P = 0.76), E(1) (P = 0.86), or E(1)S (P = 0.56). Within individuals, NAF and serum levels of E(2) (r(s) = 0.37; P < 0.001) but not of E(1)S (r(s) = 0.004; P = 0.97) were correlated. E(2) and E(1)S in NAF and serum were strongly associated (r(s) = 0.78 and r(s) = 0.48; P < 0.001).

Soy foods in amounts consumed by Asians did not significantly modify estrogen levels in NAF and serum.

The trend toward lower estrogen levels in NAF during the high-soy diet counters concerns about adverse effects of soy foods on breast cancer risk.