Breast Cancer Risk in Women With Abnormal Cytology in Nipple Aspirates of Breast Fluid

Wrensch, Margaret; Petrakis, Nicholas L.; Miike, Rei; King, Eileen B.; Chew, Karen; Neuhaus, John; Lee, Marion M.; Rhys, Moore

doi:10.1093/jnci/93.23.1791

Cited by 161 publications

(132 citation statements)

References 44 publications

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“…Although NAF is traditionally used for cytological assessments (4)(5)(6), it can also be used to study protein expression patterns by proteomic technologies.…”

Section: Introductionmentioning

confidence: 99%

Detection of breast cancer biomarkers in nipple aspirate fluid by SELDI-TOF and their identification by combined liquid chromatography-tandem mass spectrometry

Gornbein²,

Shen³

et al. 2007

Int J Oncol

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Abstract. Screening mammography is the most effective tool available for breast cancer detection. While screening mammography saves lives, it has intrinsic problems that limit further improvement. We hypothesize that protein biomarkers in nipple aspirate fluid (NAF) may separate the cancer from the non-cancer state, and therefore can be used for breast cancer detection. In this study the proteins in NAF were analyzed by surface-enhanced laser desorption ionization coupled to time-of-flight mass spectrometry (SELDI-TOF) in the m/z 5,000-85,000 range. Two methods were used to normalize spectra. Then differentially expressed signals that separate cancer from non-cancer conditions were selected by two specifically developed statistical algorithms. Proteins of interest were identified by combined liquid chromatographytandem mass spectrometry. A set of 8 markers were identified which collectively gave 63% sensitivity, 89% specificity and 76% accuracy for distinguishing cancer from non-cancer. Further improvements in the specificity and sensitivity of this strategy could come from the development of methods for more precise quantification of the biomarkers of interest and also from focusing on the low abundant components that are not evident when unfractionated NAF is analyzed directly.

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“…Although NAF is traditionally used for cytological assessments (4)(5)(6), it can also be used to study protein expression patterns by proteomic technologies.…”

Section: Introductionmentioning

confidence: 99%

Detection of breast cancer biomarkers in nipple aspirate fluid by SELDI-TOF and their identification by combined liquid chromatography-tandem mass spectrometry

Gornbein²,

Shen³

et al. 2007

Int J Oncol

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“…1,2 In the few studies that have examined the breast cancer risk associated with cytologic atypia, a finding of cytologic atypia was associated with a breast cancer risk similar to that reported in women with a finding of atypical hyperplasia on examination of histologic sections. 2,3 Although the cytologic criteria used to categorize intraductal epithelial changes are well defined, they have not been uniformly applied, and they have not been proven to be reproducible. 4,5 In studies that have compared cytologic findings of atypia with histologic findings from corresponding tissue, the correlation was poor and the rate of false-positive results high.…”

mentioning

confidence: 99%

Correlation of cytologic findings and chromosomal instability detected by fluorescence in situ hybridization in breast fine-needle aspiration specimens from women at high risk for breast cancer

et al. 2006

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Cytologic evaluation of ductal lavage or random periareolar fine-needle aspiration (FNA) specimens has been proposed to improve risk stratification of women at high risk for breast cancer. However, cytologic assessment of morphologic changes is subjective. To assess the utility of fluorescence in situ hybridization (FISH) in the categorization of breast lesions, we prospectively evaluated 32 random periareolar FNA specimens from 27 women at high risk for breast cancer. Cytologic specimens were prepared using the thin preparation technique, and diagnoses were made on the basis of previously published criteria. Specimens were also evaluated by FISH for chromosomes 1, 8, 11, and 17. Monosomy was defined as the loss of one signal or both signals in 420% of cells, and polysomy was defined as the presence of Z3 signals in 46% of cells. Cytologic smears from seven invasive ductal carcinomas and nine benign breast specimens from women at low risk for breast cancer were included for comparison. In the high-risk group, cytologic findings were nonproliferative epithelium (NPE) in 16 cases and hyperplasia in 16 cases. Chromosomal aberrations were detected in 11 (69%) of 16 NPE cases, 14 (89%) of 16 hyperplasia cases, seven (100%) of seven carcinoma cases, and none of the low-risk cases. Highrisk cases had significantly more monosomy of chromosomes 1, 11, and 17 and polysomy of chromosome 8 compared to low-risk cases and significantly less polysomy of chromosomes 1, 8, 11, and 17 compared to patients with cancer. There were no significant differences in monosomy or polysomy of individual chromosomes or a combination of chromosomes between the NPE and hyperplasia groups. This study shows that aberrations of chromosome number are common in high-risk women irrespective of cytologic findings. Studies evaluating the association between specific patterns of chromosomal polysomy and progression to malignancy may be warranted.

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“…There has been renewed interest in using the cytologic changes in the epithelial cells obtained from these specimens for risk stratification of women at increased risk for developing breast carcinoma. 1,2 Although there is abundant literature describing the cytologic criteria for classification, the cytologic categorization of the epithelial cells in these specimens as benign, mildly atypical, markedly atypical, and malignant is largely subjective. We know of no immunocytochemical stains that can be used as ancillary markers to overcome the problem of subjectivity in the cytologic interpretation of cells or for understanding the significance of morphologic changes in cells.…”

mentioning

confidence: 99%

Feasibility and utility of using chromosomal aneusomy to further define the cytologic categories in nipple aspirate fluid specimens

Krishnamurthy

Zhao

Hayes

et al. 2004

Cancer

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Breast Cancer Risk in Women With Abnormal Cytology in Nipple Aspirates of Breast Fluid

Abstract: The results obtained with the newly followed women independently confirmed previous findings that women with abnormal cytology in nipple aspirates of breast fluid have an increased risk of breast cancer.

Cited by 161 publications

References 44 publications

Detection of breast cancer biomarkers in nipple aspirate fluid by SELDI-TOF and their identification by combined liquid chromatography-tandem mass spectrometry

Detection of breast cancer biomarkers in nipple aspirate fluid by SELDI-TOF and their identification by combined liquid chromatography-tandem mass spectrometry

Correlation of cytologic findings and chromosomal instability detected by fluorescence in situ hybridization in breast fine-needle aspiration specimens from women at high risk for breast cancer

Feasibility and utility of using chromosomal aneusomy to further define the cytologic categories in nipple aspirate fluid specimens

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