Skip to main content

Advertisement

SpringerLink
Log in

A strong association between body fat mass and protein profiles in nipple aspirate fluid of healthy premenopausal non-lactating women

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Fluid can be aspirated from the nipples of most non-lactating women. This nipple aspirate fluid (NAF) is a potential source for the discovery of new breast cancer biomarkers. NAF has two distinct protein profiles. Type I NAF is similar to the fluid associated with cystic disease of the breast, whereas type II NAF is enriched in milk-associated proteins. The prevalence of these two profiles differs in healthy women and in breast cancer patients. This study investigated the relationship of these two NAF profiles to reproductive history, body composition, diet, and levels of lipids, steroids and thyroid hormones in healthy premenopausal women (age 30–40 years) who had regular menstrual cycles and normal mammograms and were not taking contraceptive medications. On average, women with the type I NAF profile were older, had more years since last childbirth, were less likely to have breastfed their babies and had higher dietary saturated fat intake, body mass index, body fat mass, and levels of plasma low density lipoproteins than women with the type II profile (P <0.05). Using multiple logistic regression, type I NAF was predicted independently (P <0.05) by higher body fat mass [Odds Ratio (OR) = 3.0; 95% Confidence Interval (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 or types of dietary and body fat, but further study of the relationship of the two profiles to breast cancer risk is needed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

NAF:

nipple aspirate fluid

ZAG:

zinc α2-glycoprotein

apoD:

apolipoprotein D

GCDFP-15:

gross cystic disease fluid protein 15 (prolactin-inducible protein)

BMI:

body mass index

DEXA:

dual energy X-ray absorptiometry

T3:

triiodothyronine

T4:

tetraiodothyronine

TSH:

thyroid stimulating hormone

HDL:

high density lipoprotein

LDL:

low density lipoprotein

VLDL:

very low density lipoprotein;

MALDI-TOF MS:

matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

References

  1. Petrakis NL (1986) Physiologic, biochemical, and cytologic aspects of nipple aspirate fluid. Breast Cancer Res Treat 1:7–19

    Article  Google Scholar 

  2. Klein P, Glaser E, Grogan L, Keane M, Lipkowitz S, Soballe P, Brooks L, Jenkins J, Steinberg SM, DeMarini DM, Kirsch I (2001) Biomarker assays in nipple aspirate fluid. Breast J 6:378–387

    Article  Google Scholar 

  3. Djuric Z, Visscher DW, Heilbrun LK, Chen G, Atkins M, Covington CY (2005) Influence of lactation history on breast nipple aspirate fluid yields and fluid composition. Breast J 2:92–99

    Article  Google Scholar 

  4. Lee MM, Petrakis NL, Wrensch MR, King EB, Miike R, Sickles E (1994) Association of abnormal nipple aspirate cytology and mammographic pattern and density. Cancer Epidemiol Biomarkers Prev 1:33–36

    Google Scholar 

  5. Sauter ER, Chervoneva I, Diamandis A, Khosravi JM, Litwin S, Diamandis EP (2002) Prostate-specific antigen and insulin-like growth factor binding protein-3 in nipple aspirate fluid are associated with breast cancer. Cancer Detect Prev 2:149–157

    Article  Google Scholar 

  6. Sanchez LM, Vizoso F, Diez-Itza I, Lopez-Otin C (1992) Identification of the major protein components in breast secretions from women with benign and malignant breast diseases. Cancer Res 1:95–100

    Google Scholar 

  7. Hu S, Xie Y, Ramachandran P, Ogorzalek Loo RR, Li Y, Loo JA, Wong DT (2005) Large-scale identification of proteins in human salivary proteome by liquid chromatography/mass spectrometry and two-dimensional gel electrophoresis-mass spectrometry. Proteomics 6:1714–1728

    Article  CAS  Google Scholar 

  8. Tada T, Ohkubo I, Niwa M, Sasaki M, Tateyama H, Eimoto T (1991) Immunohistochemical localization of Zn-alpha 2-glycoprotein in normal human tissues. J Histochem Cytochem 9:1221–1226

    Google Scholar 

  9. Ghafouri B, Kihlstrom E, Stahlbom B, Tagesson C, Lindahl M (2003) PLUNC (palate, lung and nasal epithelial clone) proteins in human nasal lavage fluid. Biochem Soc Trans Pt 4:810–814

    Article  Google Scholar 

  10. Bundred NJ, Scott WN, Davies SJ, Miller WR, Mansel RE (1991) Zinc alpha-2 glycoprotein levels in serum and breast fluids: a potential marker of apocrine activity. Eur J Cancer 5:549–552

    Google Scholar 

  11. Haagensen DE, Stewart P, Dilley WG, Wells SA (1992) Secretion of breast gross cystic disease fluid proteins by T47D breast cancer cells in culture–modulation by steroid hormones. Breast Cancer Res Treat 1–2:77–86

    Article  Google Scholar 

  12. Simard J, de Launoit Y, Haagensen DE, Labrie F (1992) Additive stimulatory action of glucocorticoids and androgens on basal and estrogen-repressed apolipoprotein-D messenger ribonucleic acid levels and secretion in human breast cancer cells. Endocrinology 3:1115–1121

    Article  Google Scholar 

  13. Boutteville C, Revillion F, Vandewalle B, Lefebvre J (1989) [Hormonal regulation of GCDFP-15 secretion in breast tumors. Study of cultured cells]. Bull Cancer 8:805–811

    Google Scholar 

  14. Simard J, Hatton AC, Labrie C, Dauvois S, Zhao HF, Haagensen DE, Labrie F (1989) Inhibitory effect of estrogens on GCDFP-15 mRNA levels and secretion in ZR-75–1 human breast cancer cells. Mol Endocrinol 4:694–702

    Article  Google Scholar 

  15. Simard J, Dauvois S, Haagensen DE, Levesque C, Merand Y, Labrie F (1990) Regulation of progesterone-binding breast cyst protein GCDFP-24 secretion by estrogens and androgens in human breast cancer cells: a new marker of steroid action in breast cancer. Endocrinology 6:3223–3231

    Google Scholar 

  16. Murphy LC, Tsuyuki D, Myal Y, Shiu RP (1987) Isolation and sequencing of a cDNA clone for a prolactin-inducible protein (PIP). Regulation of PIP gene expression in the human breast cancer cell line, T-47D. J Biol Chem 31:15236–15241

    Google Scholar 

  17. Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA (2000) Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression. FASEB J 12:1725–1730

    Article  Google Scholar 

  18. Topper YJ, Freeman CS (1980) Multiple hormone interactions in the developmental biology of the mammary gland. Physiol Rev 4:1049–1106

    Google Scholar 

  19. Ray DB, Horst IA, Jansen RW, Kowal J (1981) Normal mammary cells in long term culture. I. development of hormone-dependent functional monolayer cultures and assay of alpha-lactalbumin production. Endocrinology 2:573–583

    Google Scholar 

  20. Teng CT, Pentecost BT, Chen YH, Newbold RR, Eddy EM, McLachlan JA (1989) Lactotransferrin gene expression in the mouse uterus and mammary gland. Endocrinology 2:992–999

    Article  Google Scholar 

  21. Vizoso F, Plaza E, Vazquez J, Serra C, Lamelas ML, Gonzalez LO, Merino AM, Mendez J (2001) Lysozyme expression by breast carcinomas, correlation with clinicopathologic parameters, and prognostic significance. Ann Surg Oncol 8:667–674

    Article  PubMed  CAS  Google Scholar 

  22. Webster J, Oxley D (2005) Peptide mass fingerprinting: protein identification using MALDI-TOF mass spectrometry. Methods Mol Biol 227–240

  23. Rose DP (1992) Hormones and growth factors in nipple aspirates from normal women and benign breast disease patients. Cancer Detect Prev 1:43–51

    Google Scholar 

  24. Vizoso F, Sanchez LM, Diez-Itza I, Luz LM, Lopez-Otin C (1992) Factors affecting protein composition of breast secretions from nonlactating women. Breast Cancer Res Treat 3:251–258

    Article  Google Scholar 

  25. Vizoso F, Diez-Itza I, Sanchez LM, Tuya AF, Ruibal A, Lopez-Otin C (1994) Relationship between serum prolactin levels and protein composition of breast secretions in nonlactating women. J Clin Endocrinol Metab 2:525–529

    Article  Google Scholar 

  26. Bray GA (2002) The underlying basis for obesity: relationship to cancer. J Nutr 11(Suppl):3451S–3455S

    Google Scholar 

  27. Bray GA (2004) Medical consequences of obesity. J Clin Endocrinol Metab 6:2583–2589

    Article  CAS  Google Scholar 

  28. Irwin ML, McTiernan A, Bernstein L, Gilliland FD, Baumgartner R, Baumgartner K, Ballard-Barbash R (2005) Relationship of obesity and physical activity with C-peptide, leptin, and insulin-like growth factors in breast cancer survivors. Cancer Epidemiol Biomarkers Prev 12:2881–2888

    Article  Google Scholar 

  29. Quinkler M, Sinha B, Tomlinson JW, Bujalska IJ, Stewart PM, Arlt W (2004) Androgen generation in adipose tissue in women with simple obesity–a site-specific role for 17beta-hydroxysteroid dehydrogenase type 5. J Endocrinol 2:331–342

    Article  CAS  Google Scholar 

  30. Liu Z, Chang GQ, Leibowitz SF (2001) Apolipoprotein D interacts with the long-form leptin receptor: a hypothalamic function in the control of energy homeostasis. FASEB J 7:1329–1331

    Google Scholar 

  31. Bing C, Bao Y, Jenkins J, Sanders P, Manieri M, Cinti S, Tisdale MJ, Trayhurn P (2004) Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia. Proc Natl Acad Sci U S A 8:2500–2505

    Article  CAS  Google Scholar 

  32. Gohda T, Makita Y, Shike T, Tanimoto M, Funabiki K, Horikoshi S, Tomino Y (2003) Identification of epistatic interaction involved in obesity using the KK/Ta mouse as a Type 2 diabetes model: is Zn-alpha2 glycoprotein-1 a candidate gene for obesity? Diabetes 8:2175–2181

    Article  Google Scholar 

  33. Manni A, Santen RJ, Boucher AE, Lipton A, Harvey H, Drago J, Rohner T, Haagensen D, Glode M, Santner SJ (1984) Evaluation of CEA and GCDFP-15 plasma level during hormonally induced cancer stimulation. Anticancer Res 3:141–144

    Google Scholar 

  34. Haagensen DE, Jr., Dilley WG, Mazoujian G, Wells SA, Jr (1990) Review of GCDFP-15. An apocrine marker protein. Ann N Y Acad Sci 161–173

  35. 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 22:7500–7510

    Article  Google Scholar 

  36. Wrensch MR, Petrakis NL, Gruenke LD, Ernster VL, Miike R, King EB, Hauck WW (1990) Factors associated with obtaining nipple aspirate fluid: analysis of 1428 women and literature review. Breast Cancer Res Treat 1:39–51

    Article  Google Scholar 

Download references

Acknowledgements

We thank the staff of the GCRC at UTMB for nursing and dietary research assistance. Special thanks to study volunteers, Dr. Astrid Inniss for the analysis of food records, Dr. Marinel Ammenheuser for critical review of the manuscript, and the Mother’s Milk Bank at Austin for providing human breast milk samples.

Author information

Authors and Affiliations

  1. Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, 700 Harborside Drive, Galveston, TX, 77555-1109, USA

    Yafei Huang, Karl E. Anderson, James J. Grady & Lee-Jane W. Lu

  2. Obstetrics and Gynecology , The University of Texas Medical Branch, Galveston, TX, 77555-1109, USA

    Manubai Nagamani

  3. Biochemistry & Molecular Biology, The University of Texas Medical Branch, Galveston, TX, 77555-1109, USA

    Alexander Kurosky & Anthony M. Haag

Authors
  1. Yafei Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manubai Nagamani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karl E. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexander Kurosky
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anthony M. Haag
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. James J. Grady
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lee-Jane W. Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lee-Jane W. Lu.

Additional information

Grant support: U.S. Army MRMC under DAMD17-01-1-0417, NIH NCRR GCRC M01 RR00073, NIH R01 CA95545, U.S. Army MRMC under W81XWH-04-1-0345, NIH 2 P30 ES06676, 1 R24 CA88317, AICR grant 01B110, and USPHS CA65628.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, Y., Nagamani, M., Anderson, K.E. et al. A strong association between body fat mass and protein profiles in nipple aspirate fluid of healthy premenopausal non-lactating women. Breast Cancer Res Treat 104, 57–66 (2007). https://doi.org/10.1007/s10549-006-9388-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-006-9388-4

Keywords

Search

Navigation