Cytologic Evaluation of Breast Fluid in the Detection of Breast Disease
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Sartorius, Otto W.; Smith, Helene S.; Morris, Peter J.; Benedict, Doris; Friesen, Lawrence

doi:10.1093/jnci/59.4.1073

Cited by 132 publications

(97 citation statements)

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“…The tubing is attached to a standard syringe that is used to create a gentle vacuum. This device was originally used and described by Sartorius et al (4) and was purchased for the collection of NAF from CYTYC Health Corp. (Boxborough, MA).…”

Section: Nipple Aspiration Fluidmentioning

confidence: 99%

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Identification of Biomarkers for Breast Cancer in Nipple Aspiration and Ductal Lavage Fluid

Li¹,

Zhao²,

Yu³

et al. 2005

Clinical Cancer Research

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Purpose: To establish a comprehensive proteomic approach for biomarker discovery and validation in breast fluid. Experimental Design: A total of 95 specimens from three institutions were used including 10 nipple aspiration fluid (5 stage I/II cancerous breasts and 5 age-matched healthy controls), 42 ductal lavage fluid from 14 patients with unilateral stage I/II cancer (25 from 9 cancerous breasts and 17 from 7 contralateral breasts), and 42 ductal lavage fluid from 14 high-risk women (multiple ducts repeated lavage). Differentially expressed protein/peptides were discovered by proteomic analysis of training sample, using ProteinChip arrays and surface-enhanced laser desorption ionization (SELDI) time-of-flight mass spectrometry, and validated on independently collected testing samples. After protein identification, ELISA was done to confirm the SELDI findings. Results: We were able to obtain reproducible protein profiles using minimal amount of protein (1 Ag) by applying an optimized chip protocol and SELDI.We were able to select cancer-associated biomarkers despite large individual variability by applying both unsupervised and supervised cluster analysis. Furthermore, we were able to train and test candidate biomarkers on independently collected samples and identified one component of a multimarker panel as human neutrophil peptides 1to 3. Conclusions: Breast fluid is a rich source of breast cancer biomarkers. In combination with highthroughput novel proteomic profiling technology and multicenter study design, markers that are highly specific to breast cancer can be discovered and validated. Our observations also suggest that persistent elevation of human neutrophil peptide in high-risk women may imply early onset of cancer not yet detectable by current detection method. Proof of this hypothesis requires follow-up on a larger study population.Breast cancer is the most commonly diagnosed cancer among women. Presymptomatic screening to detect early-stage breast cancer while it is still resectable could potentially reduce breast cancer-related mortality. Unfortunately, only 63% (1992-1999, United States) of the breast cancers are localized at the time of diagnosis (1). Small lesions are frequently missed and may not be visible even by mammography, particularly in young women and women with dense breast tissue (2). Molecular markers that can potentially identify these small lesions that are invisible to imaging techniques will provide a real opportunity to treat a neoplasm before it invades the tissue.Breast cancer is highly heterogeneous. Most molecularly based approaches that have been investigated for the early detection of breast cancer are targeted at specific factors, such as oncogenes, tumor suppressor genes, growth factors, tumor antigens, or other gene products. The inherent problem is that none of these factors alone can account for a large majority of the breast cancers and some are not specific to cancer or breast tissues; thus, the sensitivity and specificity of such approaches is low. Thus f...

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Section: Nipple Aspiration Fluidmentioning

confidence: 99%

“…These droplets were collected with capillary tubes. This technique is successful in most women (4) and the yield typically varies from several microliters to 100 AL (5, 6). As nipple aspiration fluid (NAF) comes only from the immediate vicinity of the nipple and the yield of which is unpredictable, a ductal lavage system has been devised.…”

mentioning

confidence: 99%

Identification of Biomarkers for Breast Cancer in Nipple Aspiration and Ductal Lavage Fluid

Li¹,

Zhao²,

Yu³

et al. 2005

Clinical Cancer Research

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“…Most women at increased risk for breast cancer by virtue of family history or other factors have never had a diagnostic biopsy. (Sartorius et al 1977). Ability to produce NAF is influenced by cohort selection and the number of attempts (Sauter et al 1996, Klein et al 2001, Wrensch et al 2001.…”

Section: Established Risk Biomarkersmentioning

confidence: 99%

Breast-tissue sampling for risk assessment and prevention

Fabian

Kimler

Mayo

et al. 2005

Endocrine Related Cancer

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Breast tissue and duct fluid provide a rich source of biomarkers to both aid in the assessment of shortterm risk of developing breast cancer and predict and assess responses to prevention interventions. There are three methods currently being utilized to sample breast tissue in asymptomatic women for risk assessment: nipple-aspirate fluid (NAF), random periareolar fine-needle aspiration (RPFNA) and ductal lavage. Prospective single-institution trials have shown that the presence of atypical cells in NAF fluid or RPFNA specimens is associated with an increased risk of breast cancer. Furthermore, RPFNA-detected atypia has been observed to further stratify risk based on the commonly used Gail risk-assessment model. A prospective trial evaluating risk prediction on the basis of atypical cells in ductal-lavage fluid is ongoing. The ability of other established non-genetic biomarkers (mammographic breast density; serum levels of bioavailable estradiol, testosterone, insulin-like growth factor-1 and its insulin like growth factor binding protein-3) to stratify risk based on the Gail model is as yet incompletely defined. Modulation of breast intra-epithelial neoplasia (i.e. hyperplasia with or without atypia) with or without associated breast-tissue molecular markers, such as proliferation, is currently being used to evaluate response in Phase II chemoprevention trials. RPFNA has been the method most frequently used for Phase II studies of 6-12 months duration. However, ductal lavage, RPFNA and random and directed core needle biopsies are all being utilized in ongoing multi-institutional Phase II studies. The strengths and weaknesses of each method are reviewed.

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“…Decades later, the development of a modified breast pump by Sartorius rejuvenated interest in the technology [Sartorius et al, 1997]. Fluid could then be obtained in up to 60% of the subjects sampled [Sartorius et al, 1997]. The aspirator is placed over the nipple and gentle suction draws the fluid to the surface of the nipple.…”

Section: Breast Ductal Fluidmentioning

confidence: 99%

Lavage and nipple aspiration of breast ductal fluids: A source of biomarkers for environmental mutagenesis

Klein¹,

Lawrence

2002

Environ and Mol Mutagen

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The acquisition of breast ductal fluid by nipple aspiration and ductal lavage are simple noninvasive procedures to sample breast tissue. Nipple aspiration fluid (NAF) obtained with gentle suction and a simple syringe‐adapted apparatus may evaluate the secretory components that bathe the ductal epithelial cells. Evaluations have included the quantification of soluble markers (carcinoembryonic antigen and prostatic‐specific antigen), DNA amplification, protein gel electrophoresis, and mutagenesis assays. It has been suggested that environmental mutagens in the breast ductal system may contribute to carcinogenesis. The feasibility of mutagenesis assays on NAF has been limited by the small size of the samples obtained. Three small clinical studies detected mutagens in 6–14% of the samples using the Salmonella Ames assay. Ductal lavage collects more of a cellular aspirate from the ductal system utilizing a microcatheter. Early studies on ductal lavage fluid have included cytology and methylation‐specific PCR. Ductal lavage in a high‐risk group has identified cellular atypia in 21% of those sampled. Samples obtained through the nipple, by aspiration or lavage, are the proteinaceous secretions from the ductal system and ductal epithelial cells. The fluid represents the cellular events and the dynamic secretory process of the breast and may include potential initiators of the carcinogenesis process in the cellular microenvironment. Fluid obtained by ductal lavage may allow for more detailed studies of the role of mutagens in breast cancer. Environ. Mol. Mutagen. 39:127–133, 2002. © 2002 Wiley‐Liss, Inc.

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Cytologic Evaluation of Breast Fluid in the Detection of Breast Disease 2

Cited by 132 publications

References 0 publications

Identification of Biomarkers for Breast Cancer in Nipple Aspiration and Ductal Lavage Fluid

Identification of Biomarkers for Breast Cancer in Nipple Aspiration and Ductal Lavage Fluid

Breast-tissue sampling for risk assessment and prevention

Lavage and nipple aspiration of breast ductal fluids: A source of biomarkers for environmental mutagenesis

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