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Objective: Determine whether differences in serum hormone concentrations explain the lack of NAF yield among women participating in a study of NAF hormone concentrations in breast cancer cases and screening controls. Methods: 80 NAF yielders (Y) and 80 non-yielders (NY) were randomly selected from women who had completed participation in an ongoing case-control study, equally divided by menopausal status and case-control status (only the contralateral breast was aspirated in cases). Average age of premenopausal women was 45.95 years and of postmenopausal women was 57.54 years. The percentage of African American and Caucasian subjects was similar among those who yielded NAF and those who did not. Serum was collected on the same day that nipple aspiration was attempted and the serum was assayed for estradiol, progesterone, and FSH by standard immunoassays. Hormonal concentrations were compared among 80 subjects who produced >2 microliters of NAF and 80 who did not. Wilcoxon tests were used to compare rank distributions of the values for yielders and non-yielders within each menopausal and case/control category. Results: Hormonal data were analyzed in quintiles with the following comparisons: premenopausal cases Y vs NY; postmenopausal cases Y vs NY; premenopausal controls N vs NY; postmenopausal controls N vs NY. Among premenopausal cases estradiol was significantly greater at the P = 0.0067 level among those who did not produce NAF. This remained significant after correction for multiple comparisons. The difference remained significant after combining cases and controls at the P = 0.021 level. The other comparisons were not significant. Analyses of progesterone and FSH yielded no significant differences. Discussion: The inhibition of breast fluid accumulation by estradiol is consistent with the effect of ovarian steroids on milk secretion observed after parturition. The observation that this effect was greater in cases is interesting and will be investigated further to ascertain whether other factors associated with breast cancer may play a role in the observed inhibition. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B33.

Background: Breast cancer risk is related to endogenous lifetime steroid hormone exposure. The local production of steroid hormones in the breast is a stable contributor to the hormonal environment. Several risk marker proteins have been identified in nipple aspirate fluid (NAF) in unaffected contralateral breast or in high-risk subjects as indicators of changes in breast on oxidative stress (superoxide dismutase), inflammation (C-reactive protein and YKL40), protease activity (cathepsin D) and growth factors (bFGF). However, it is not clear whether the alteration of protein markers is related to the local steroid hormone synthesis and metabolism in the breast. In the study, we studied the correlation between protein markers and both systematic (serum) and local (NAF) abundance of hormones. Methods: NAF and blood samples were obtained from normal breast of 54 healthy women and from unaffected breast of 60 breast cancer patients. The 114 subjects consisted of 48 women in premenopausal, 54 in postmenopausal and 12 in perimenopausal. The abundance of five protein markers (SOD1, CRP, YKL40, CatD and bFGF) was measured using ELISA. The NAF concentration of estradiol (E2), estrone (E1), progesterone (P4), andostenedione (A4), testosterone (T), dehydroepiandrostrerone (DHEA) and DHEA sulfate (DHEAS), and the serum concentration of E2, E1, P4, A4, T, DHEA and follicular-stimulating hormone (FSH) were measured using ELISA or RIA. The correlation between protein markers and hormones were examined using Spearman's rank correlation test with Bonferroni adjusted p < 0.05 as statistical significant. Results: The correlation among the protein markers showed that SOD1 was significantly correlated with CRP (r=0.276, p=0.033) and catD (r=0.340, p=0.0036). bFGF was significantly correlated with CRP (r=0.343, p=0.0021), indicating these proteins may be affected each other in the breast. The relationship between protein markers and hormones indicated that protein markers did not have much correlation with serum hormones, except bFGF was negatively correlated with serum T level (r=−0.339, p=0.017). In contrast, protein markers showed stronger correlation with multiple estradiol precursors in NAF. Specifically, SOD1 correlated with DHEA (r=0.333, P=0.019) and DHEAS (r=0.372, p=0.0030). YKL40 correlated with NAF T level (r=0.389, p=0.0012). CatD correlated with NAF DHEAS (r=0.400, p=0.0014). bFGF negatively correlated with NAF T (r=−0.339, p=0.015). CRP did not show significant correlation with any types of measured NAF hormones. Conclusions: NAF protein markers were more strongly related to local hormone levels in the breast, rather than systematic hormones in the blood. Protein markers were specifically correlated with different components of hormone hormones, suggesting that metabolic precursors may contribute to breast cancer risk through distinct mechanisms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5756. doi:1538-7445.AM2012-5756