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Significant differences in nipple aspirate fluid protein expression between healthy women and those with breast cancer demonstrated by time-of-flight mass spectrometry

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Abstract

New approaches are needed for the early detection of breast cancer. Proteomic profiling technologies, such as surface-enhanced laser desorption ionization mass spectrometry (SELDI-MS), may be able to identify tumor markers in biological fluids. The objective of this study was to determine whether there are differences in protein expression patterns in nipple aspirate fluid (NAF) from the cancerous and noncancerous breasts of patients with unilateral breast cancer and the breasts of healthy volunteers. Paired NAF samples were obtained from 23 women with stage I or II unilateral invasive breast carcinoma and five healthy female volunteers. Aliquots of the samples were applied to SELDI Protein-chip arrays (WCX2 and IMAC3-Cu++), and protein expression was analyzed using time-of-flight MS. A total of 463 distinct peaks were detected and analyzed. In breast cancer patients, no differences in protein expression were identified between the breast with the intact primary carcinoma and the contralateral noncancerous breast. Seventeen peaks were overexpressed in cancer-bearing breasts compared to breasts of healthy volunteers (p < 0.0005). When spectra from the nontumor-bearing breasts of breast cancer patients were compared with spectra from breasts of healthy volunteers, two peaks that were overexpressed in breast cancer patients and one peak that was underexpressed in breast cancer patients were detected (p < 0.0027). SELDI-MS was able to identify differences in the phenotypic proteomic profile of NAF samples obtained from patients with early-stage breast cancer and healthy women. Proteomic screening techniques such as SELDI-MS analysis of NAF may be useful for breast cancer screening and diagnosis.

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Authors and Affiliations

  1. Department of Surgical Oncology, Unit 444, The University of Texas, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Timothy M. Pawlik, Kelly K. Hunt & Henry M. Kuerer

  2. Department of Laboratory Medicine, The University of Texas, Houston

    Herbert Fritsche

  3. Department of Biostatistics, The University of Texas, Houston

    Kevin R. Coombes & Lianchun Xiao

  4. Department of Pathology, The University of Texas, Houston

    Savitri Krishnamurthy

  5. Department of Breast Medical Oncology, The University of Texas, Houston

    Lajos Pusztai & Banu Arun

  6. Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX

    Jeng-Neng Chen & Mien-Chie Hung

  7. Ciphergen Biosystems, Inc., Fremont, CA, USA

    Charlotte H. Clarke

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  1. Timothy M. Pawlik
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  2. Herbert Fritsche
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  3. Kevin R. Coombes
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  4. Lianchun Xiao
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  8. Jeng-Neng Chen
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  9. Charlotte H. Clarke
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  10. Banu Arun
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  12. Henry M. Kuerer
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Correspondence to Henry M. Kuerer.

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Pawlik, T.M., Fritsche, H., Coombes, K.R. et al. 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 (2005). https://doi.org/10.1007/s10549-004-1710-4

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