Early markers of breast cancer in nipple aspirate fluid

Date
2007-07-12
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Abstract

Nipple aspirate fluid (NAF) refers to the small amount of secretion that is found in breast ducts/lobules of most non-lactating women. This fluid can be collected repeatedly and non-invasively via the nipple using a modified breast pump, and therefore, it is considered to be a potential source for identifying markers of breast cancer. The purpose of this study was to understand factors associated with the ability to secrete fluid and factors associated with the major protein profiles in NAF; and to identify protein profiles of NAF in a group of healthy non-lactating women who were 30-40 years old, not pregnant, not breastfeeding, and not taking contraceptive medications.\r\n\r\nAmong 238 women studied, 66% were secretors of NAF. Using multivariate logistic regression models, higher dietary intake of lactose [Odds Ratio (OR)=2.7; 95% Confidence Interval (CI): 1.5-4.8], earlier menarche (OR=0.8, CI: 0.7-1.0), being parous (OR=2.3, CI: 1.0-5.6), and older at first childbirth (OR=1.5, CI: 1.0-2.1) were found to be independent and positive predictors for being a secretor of NAF. These findings suggest that dietary intake of lactose, a modifiable factor, may be used to change the NAF secretor status of women. \r\n\r\nNAF were analyzed for major proteins. Two major types of protein profiles, type I and type II, were identified. Type I NAF contains proteins found in cystic disease fluid of the breast, whereas type II NAF is enriched in milk-associated proteins. Using multiple logistic regression, type I NAF was predicted independently (P<0.05) by higher body fat mass (Odds Ratio=3.0; CI: 1.5-6.1), more years since last childbirth (OR=2.6; 95% CI: 1.3-5.2) and a higher percentage of calories from saturated fat (OR=4.1; 95% CI: 1.1-14.6). These results suggest that protein profiles of NAF might be influenced by amounts and/or types of dietary and body fat. \r\n\r\nTwo different analytical strategies, 2D gel analysis coupled with MALDI-TOF/TOF, and 1D gel coupled with LC-MS/MS, were used to characterize protein profiles of type I and II NAF. Using these two strategies, a total of 99 proteins were identified: 13 unique to type I NAF, 57 unique to type II NAF, and 29 common to both types. These strategies will be used to characterize proteins in NAF of breast cancer cases. \r\n

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Keywords
proteomics, breast secretion, biomarker
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