Nipple aspirate fluid: a promising non-invasive method to identify cellular markers of breast cancer risk

Sauter, Edward R.; Ross, Eric A.; Daly, Mary; Klein‐Szanto, Andres J.; Engstrom, Paul F.; Sorling, A.; Malick, John; Ehya, Hormoz

doi:10.1038/bjc.1997.415

Cited by 177 publications

(167 citation statements)

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“…Such activity was not observed in NAF from women with benign breast disease [Malatesta et al, 2000]. The NAF cells, from the ipsilateral breast of breast cancer patients, have been more likely to contain a higher DNA index (DNA content) and hypertetraploid features than the cells obtained by nipple aspiration from women with benign breast disease [Sauter et al, 1997]. However, both of these studies were on samples far too limited to be conclusive.…”

Section: Cellular Componentsmentioning

confidence: 92%

“…Investigations of NAF have been limited primarily because of the small quantity of fluid obtained. Moreover, there are limited long-term data [Sauter et al, 1997]. Researchers anticipate that ductal fluid obtained from ductal lavage will be more informative than NAF because of the larger quantity, the increased cellularity, and greater probability of obtaining fluid from a given individual.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Cellular Componentsmentioning

confidence: 92%

Section: Introductionmentioning

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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“…Being the application of molecular epidemiology to nutrition and breast cancer in its infancy, recent studies have highlighted the importance of investigations of diet, genetic variability and breast cancer risk using a fluid non-invasively collected from breast ducts (nipple aspirate fluid, NAF), a fluid that mirrors the microenvironment of the breast tissue during physio-pathological conditions [29,43,44,56].…”

Section: Gene-diet Interactions and Breast Cancer Riskmentioning

confidence: 99%

“…Larger sample volumes allow to obtain a greater number of epithelial cells, useful for efficient optical and electronic microscopy studies [29][30][31]. The value of NAF has been extensively described [12,30,31,43,56], referring to breast secretions as quick, repeatable, non-invasive means for obtaining fluid and breast ductal cells. The breast is unique among secretory glands, because many chemicals in the secretions are retained and concentrated, possibly for long periods of time, and eventually metabolized by the breast epithelium or absorbed [29,44].…”

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confidence: 99%

Nutrients and nipple aspirate fluid composition: the breast microenvironment regulates protein expression and cancer aetiology

2008

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The aetiology of breast cancer is complex and multifactorial, and may include diet and xenobiotic compounds. A change in diet affects nutrient levels in blood, but to what extent diet can affect micronutrient concentrations in the breast is not yet well established. Breast nipple aspirate fluids (NAF) can be non-invasively obtained from the breast in most women; it represents a biological tool to assess metabolic changes in the breast ductal microenvironment. A wide variation in biomolecular and hormonal composition of NAFs collected from healthy and breast cancer patient may be due to genetic and nutritional factors; however, micro-and macro-nutrients may influence the secretory status of these women, thus NAF composition and risk of breast carcinoma. The aim of this overview is to highlight the detrimental/beneficial role that diet-related compounds in nipple aspirate fluid can have in breast cancer risk.Keywords Nutrigenomics Á Diet Á Benign breast diseases Á Breast cancer Á Nipple aspirate fluids Á Nutrients Gene-diet interactions and breast cancer riskBreast cancer aetiology is complex, and many factors (both environmental and genetic) contribute to it. Of the environmental factors, the link between diet and BC risk has long been recognized [35]. Because benign breast disease (BBD), particularly atypical hyperplasia (AH), is a marker of increased BC risk, studies of diet and BBD have provided evidence about the effect of diet at an early stage in the process of breast carcinogenesis, reporting also some contrasting results [26,52]. It is well known that high consumption of fruit and vegetable has been thought to provide protection against many types of cancer, including BC [15]. Their consumption could decrease BC risk through several mechanisms, mainly linked to the abundance of antioxidants contained therein, which also contain biocompounds such as isoflavones, lignans and indoles [1,2,64]; all of these substances have been convincingly shown to have anticarcinogenic properties and strong effects on estrogen metabolism (as reviewed in [38]), even though to date there are contrasting findings [35].It is becoming clear that relationships between diet and breast cancer aetiology are extremely complex, and that the impact of micro-and macro-nutrients on BC risk are dependent in part on genetic factors [20,21,58]. Being the application of molecular epidemiology to nutrition and breast cancer in its infancy, recent studies have highlighted the importance of investigations of diet, genetic variability and breast cancer risk using a fluid non-invasively collected from breast ducts (nipple aspirate fluid, NAF), a fluid that mirrors the microenvironment of the breast tissue during physio-pathological conditions [29,43,44,56]. Nipple aspirate fluid, a window on the breast tissue microenvironmentThe ductal system of the breasts of non-pregnant women produces proteinaceous secretions-containing chemicals of endogenous and exogenous origin as well as epithelial cells-which can be sampled and utilized for breas...

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“…We were able to collect nipple aspirate fluid (NAF) from essentially all adult women. 16 We have performed nipple aspiration on over 750 women without complications. Both the cells and extracellular fluid obtained hold promise for use in cancer screening.…”

mentioning

confidence: 99%

Ethnic variation in kallikrein expression in nipple aspirate fluid

Sauter

Welch

Magklara

et al. 2002

Intl Journal of Cancer

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Socioeconomic factors cannot entirely explain why black women have an earlier age of breast cancer onset and higher mortality rates, stage for stage, than whites. We and others have shown that prostate-specific antigen [PSA, also known as human kallikrein (hK) 3] is a marker of breast as well as prostate cancer, that hK2 and hK3 are highly homologous at the DNA and protein level and that the level of progesterone, which appears to upregulate hK3, is influenced by ethnicity. We hypothesized that nipple aspiration fluid (NAF) hK2 and hK3 levels are (i) lower in black than white women; (ii) independently associated with breast cancer; (iii) influenced by menopausal status; and (iv) in combination are more informative about whether a woman has breast cancer than either marker alone. NAF was assayed for hK2 and hK3, and the results were stratified by ethnicity, presence or absence of cancer and menopausal status. Statistical analysis was then performed. When stratified by ethnicity, hK2 (p ‫؍‬ 0.003) and hK3 (p ‫؍‬ 0.027) levels in blacks were lower than in whites. hK2 was lower in premenopausal black than in white subjects, regardless of cancer status. Overall, hK2, hK3 and the ratio hK2/hK3 were lower in subjects with breast cancer than in normal subjects. hK3 was lower in postmenopausal women with breast cancer, regardless of ethnicity. hK2 and hK3 levels were higher in pre-than in postmenopausal whites. Using logistic regression and considering hK2, hK3, hK2/hK3 and ethnicity, hK3 was significantly associated with breast cancer in both pre-(p < 0.001) and postmenopausal women (p ‫؍‬ 0.023). In conclusion, whereas hK2, hK3, hK2/hK3 and ethnicity are each significantly associated with breast cancer bivariately, after entering the strongest predictor, hK3, into a logistic regression model, no other variable accounted for additional variation, although this observation is preliminary due to the limited number of black subjects in the study. © 2002 Wiley-Liss, Inc. Key words: kallikreins; breast cancer; prostate-specific antigen; ethnicityOver 1,500 Americans die each day from cancer, making it the second leading cause of death (after cardiovascular disease) in the United States. 1 Overall cancer incidence rates are higher in men than women, and black men have the highest incidence of cancer. Among women, whites have the highest incidence. 2 The ethnic variation observed in cancer incidence and survival cannot be ascribed solely to social, cultural, economic and environmental variability. 3 Among individual cancer types, ethnic differences in cancer gene expression are present that may help explain differences in cancer incidence and survival.Since its discovery more than 20 years ago, prostate-specific antigen (PSA) has been established as the most valuable tool for the early detection, staging and monitoring of prostate cancer. 4 The KLK2 gene (encoding for hK2) and the KLK3 gene (encoding for hK3 or PSA) are members of the human kallikrein family, 5 which now comprises 15 structurally similar genes that in humans c...

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Nipple aspirate fluid: a promising non-invasive method to identify cellular markers of breast cancer risk

Cited by 177 publications

References 6 publications

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

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

Nutrients and nipple aspirate fluid composition: the breast microenvironment regulates protein expression and cancer aetiology

Ethnic variation in kallikrein expression in nipple aspirate fluid

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