Abstract
A proteomic approach to nipple aspiration fluid (NAF) has been used in a number of studies comparing women with breast cancer and healthy women. However, to make useful comparisons between women with breast cancer and healthy women it is necessary to establish whether there is physiological variation in the proteomic profiles of NAF. The purpose of this study was, for the first time, to examine how the proteomic profile of NAF using surface-enhanced laser desorption ionisation time-of-flight mass spectrometry varies across the menstrual cycle in healthy pre-menopausal women. Twelve women were recruited and nipple aspiration was carried out weekly from both breasts of each subject for two menstrual cycles. Matching serum samples for luteinising hormone, follicle stimulating hormone and oestradiol were obtained at each aspiration attempt. Statistically significant peaks were found for three healthy volunteers (p < 0.05). However, the peaks that varied across the menstrual cycle were different from one healthy volunteer to another and the differences were small compared with the large variation in proteomic profiles between healthy volunteers. This study provides proof of concept that the NAF proteomic profile does not vary substantially during the menstrual cycle and that therefore it is valid to compare NAF profiles from pre-menopausal women that have been taken at different stages in the menstrual cycle.
Similar content being viewed by others
References
Varnum SM, Covington CC, Woodbury RL, Petritis K, Kangas LJ, Abdullah MS, Pounds JG, Smith RD, Zangar RC (2003) Proteomic characterization of nipple aspirate fluid: identification of potential biomarkers of breast cancer. Breast Cancer Res Treat 80:87–97
Kuerer HM, Goldknopf IL, Fritsche H, Krishnamurthy S, Sheta EA, Hunt KK (2002) Identification of distinct protein expression patterns in bilateral matched pair breast ductal fluid specimens from women with unilateral invasive breast carcinoma. High-throughput biomarker discovery. Cancer 95:2276–2282
Alexander H, Stegner AL, Wagner-Mann C, Du Bois GC, Alexander S, Sauter ER (2004) Proteomic analysis to identify breast cancer biomarkers in nipple aspirate fluid. Clin Cancer Res 10:7500–7510
Dua RS, Isacke CM, Gui GP (2006) The intraductal approach to breast cancer biomarker discovery. J Clin Oncol 24:1209–1216
Sauter ER, Zhu W, Fan XJ, Wassell RP, Chervoneva I, Du Bois GC (2002) Proteomic analysis of nipple aspirate fluid to detect biologic markers of breast cancer. Br J Cancer 86:1440–1443
Sauter ER, Shan S, Hewett JE, Speckman P, Du Bois GC (2005) Proteomic analysis of nipple aspirate fluid using SELDI-TOF-MS. Int J Cancer 114:791–796
Pawlik TM, Fritsche H, Coombes KR, Xiao L, Krishnamurthy S, Hunt KK, Pusztai L, Chen JN, Clarke CH, Arun B et al (2005) Significant differences in nipple aspirate fluid protein expression between healthy women and those with breast cancer demonstrated by time-of-flight mass spectrometry. Breast Cancer Res Treat 89:149–157
Paweletz CP, Trock B, Pennanen M, Tsangaris T, Magnant C, Liotta LA, Petricoin EF 3rd (2001) Proteomic patterns of nipple aspirate fluids obtained by SELDI-TOF: potential for new biomarkers to aid in the diagnosis of breast cancer. Dis Markers 17:301–307
Petrakis NL (1986) Physiologic, biochemical, and cytologic aspects of nipple aspirate fluid. Breast Cancer Res Treat 8:7–19
Mitchell G, Trott PA, Morris L, Coleman N, Sauter E, Eeles RA (2001) Cellular characteristics of nipple aspiration fluid during the menstrual cycle in healthy pre-menopausal women. Cytopathology 12:184–196
Mitchell G, Sibley PE, Wilson AP, Sauter E, A’Hern R, Eeles RA (2002) Prostate-specific antigen in nipple aspiration fluid: menstrual cycle variability and correlation with serum prostate-specific antigen. Tumour Biol 23:287–297
Chatterton RT Jr, Geiger AS, Khan SA, Helenowski IB, Jovanovic BD, Gann PH (2004) Variation in estradiol, estradiol precursors, and estrogen-related products in nipple aspirate fluid from normal pre-menopausal women. Cancer Epidemiol Biomarkers Prev 13:928–935
Acknowledgements
This work was supported by Breakthrough Breast Cancer and the General Clinical Research Fund at the Royal Marsden NHS Foundation Trust. We wish to thank Ms Marie-Catherine Le Bihan (Division of Basic Medical Sciences, SGUL) and Dr Gary Coulton (Division of Basic Medical Sciences and Division of Cardiac and Vascular Sciences, SGUL) for their help and advice. We also wish to thank the Biochemistry laboratory at the Royal Marsden NHS Foundation Trust for the serum testing.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Noble, J., Dua, R.S., Locke, I. et al. Proteomic analysis of nipple aspirate fluid throughout the menstrual cycle in healthy pre-menopausal women. Breast Cancer Res Treat 104, 191–196 (2007). https://doi.org/10.1007/s10549-006-9402-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-006-9402-x