Association between ductal fluid proteomic expression profiles and the presence of lymph node metastases in women with breast cancer

Surgery. 2004 Nov;136(5):1061-9. doi: 10.1016/j.surg.2004.04.011.


Background: Proteomic analysis of nipple aspiration fluid (NAF) is a noninvasive method for studying the local biologic microenvironment of the breast ducts where carcinoma originates.

Methods: NAF samples from each breast of 23 women with stage I or II unilateral invasive breast carcinoma were collected, and protein expression was analyzed comprehensively by using protein arrays and time-of-flight mass spectrometry. Blinded hierarchical clustering analysis was performed to identify potential associations between protein expression patterns and clinicopathologic factors.

Results: After analysis of all spectra, 463 distinct peaks in the mass range of 7 to 30 kD were identified in NAF samples. Blinded hierarchical clustering analysis of protein expression patterns demonstrated a conservation of these patterns between the breasts of individual patients (P=.0003 x 10(-12)). Hierarchical clustering revealed an association between protein expression patterns, and the presence and absolute number of axillary lymph nodes containing metastases (P=.038).

Conclusions: Protein expression patterns are highly conserved between cancerous and noncancerous breasts in women with unilateral invasive breast cancer; unique expression patterns may be associated with extent of disease. High-throughput proteomic methods may reveal biologically relevant proteins involved in carcinogenesis and progression of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Fluids / physiology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Contraceptive Agents, Female
  • Estrogen Replacement Therapy / statistics & numerical data
  • Female
  • Functional Laterality
  • Gene Expression Profiling*
  • Humans
  • Lymphatic Metastasis / genetics*
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasm Staging
  • Nipples / metabolism*
  • Pedigree
  • Proteome*
  • Receptors, Estrogen / analysis
  • Risk Factors


  • Contraceptive Agents, Female
  • Neoplasm Proteins
  • Proteome
  • Receptors, Estrogen