Reproducibility of cytologic atypia in repeat nipple duct lavage

Johnson-Maddux, April; Ashfaq, Raheela; Cler, B S Leslie; Naftalis, Elizabeth; Leitch, A. Marilyn; Hoover, Susan; Euhus, David M.

doi:10.1002/cncr.20884

Cited by 30 publications

(25 citation statements)

References 34 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cytologic reproducibility was low for benign, mildly atypical, and markedly atypical cells. In a study examining the reproducibility of the diagnosis of atypia using Thin Prep (Cytyc) rather than cytospin, the results were similar to the present study (2). Poor reproducibility of atypia may contribute to higher false-positive or false-negative tests; as seen in our study, a cytologic diagnosis of atypical cells can lead to additional tests and anxiety despite communication to both the physician and study participant about the lack of scientific data associating atypical cells and breast cancer development.…”

Section: Discussionsupporting

confidence: 87%

“…The reported prevalence of markedly and mildly atypical cells as well as the percentage of ICMD in premenopausal women in this study was similar to those studies that have evaluated similar populations (1,2). Overall variability in cytology and cellular yield between ductal lavage studies could be due to differences in patient population characteristics, specimen processing, or individual variations in technique.…”

Section: Discussionsupporting

confidence: 82%

“…In one study, 23 women with mild or markedly atypical cells at their baseline visit underwent repeat lavage a median of 8.3 (range, 2.3-14.3) months later (2). The diagnosis of atypia was only reproducible in 8 of 42 (19%) fluid-producing ducts.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Reliability of Nipple Aspirate and Ductal Lavage in Women at Increased Risk for Breast Cancer—a Potential Tool for Breast Cancer Risk Assessment and Biomarker Evaluation

Visvanathan

Santor

Ali

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Purpose: Ductal lavage, a technique used to sample epithelial cells from breast ducts, has potential use in risk assessment and biomarker evaluation among women at increased risk for breast cancer. However, little is known about the reliability of the procedure. Methods: We evaluated the reliability of nipple aspirate (NAF) and ductal lavage at two time points 6 months apart in women at increased risk for breast cancer. Eligible women had a 5-year Gail risk z1.66% or lifetime risk of >20%, and/or a family history or personal history of breast cancer. All ducts that produced NAF were cannulated. The k statistic was used to evaluate reliability of NAF production, cellular yield, and cytologic diagnosis. Results: Sixty-nine women (mean age, 47 years) were enrolled over 35 months. Forty-seven returned for a second visit. At baseline, 65% of premenopausal and 41% of postmenopausal women produced NAF (P = 0.05), of which 72% underwent successful lavage of at least one duct. Samples of inadequate cellular material for diagnosis were significantly more likely in postmenopausal women than in premenopausal women (P = 0.04). Of the women who returned for a second visit, 18 of 24 who produced NAF had at least one duct successfully cannulated. Twenty-four ducts in 14 women were lavaged twice. Among these ducts, cellular yield for the two time points was inconsistent (k = 0.33 F 0.13), and only fair cytologic agreement was observed (k = 0.32 F 0.15). Ductal lavage was associated with moderate discomfort. Conclusion: Currently, the use of ductal lavage is limited by technical challenges in duct cannulation, inconsistent NAF production, a high rate of inadequate cellular material for diagnosis, fair cytologic reproducibility, and low participant return rates.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 82%

See 1 more Smart Citation

The Reliability of Nipple Aspirate and Ductal Lavage in Women at Increased Risk for Breast Cancer—a Potential Tool for Breast Cancer Risk Assessment and Biomarker Evaluation

Visvanathan

Santor

Ali

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

show abstract

“…However, the process has been hampered by difficulties in sampling of nipple duct fluid as well as the lack of predictive capability by cytologic analysis. 68 In one series, the methylation status of 11 tumor suppressor genes from ductal epithelial cells predicted sporadic and hereditary cancer with an accuracy approaching 90%. 69 Importantly, it appears that methylation changes are apparent in the ductal epithelial cells obtained from nipple duct fluid regardless of the location of the primary breast tumor.…”

Section: Methylation Changes As a Biomarkermentioning

confidence: 99%

DNA Methylation: Its Role in Cancer Development and Therapy

Kurkjian¹,

Kummar²,

Murgo³

2008

Current Problems in Cancer

View full text Add to dashboard Cite

Inflammation and Methylation ChangesChanges in the genome which result in cancer promotion remain a complex interplay of aberrant methylation in the setting of a multitude of epigenetic changes. The events leading to these disruptions in methylation have been postulated; though remain to be fully elucidated. A causal relationship between inflammation and cancer has long been accepted in multiple tumor types, most prominently colon cancer; an association supported by the evidence that non-steroidal anti-inflammatory medications can potentially stop the development of colon cancer. Investigations in patients with ulcerative colitis who have a predisposition to the development of colon cancer have established a potential link between inflammation and cancer by the demonstration of hypermethylated gene promoters in early dysplastic lesions. 1 The mechanisms responsible for the contribution of inflammation to cancer remain to be fully understood. Mutagenesis resulting from the production of halogenated nucleotide precursors in activated neutrophils and eosinophils with subsequent incorporation into DNA has been demonstrated in vitro. 2,3 The link between inflammation-induced halogenated nucleotides and aberrant methylation stems from the demonstration that methyl-binding proteins cannot distinguish between methylated cytosine residues and chlorinated or brominated cytosine nucleotides. Furthermore, DNMT1 also could not distinguish between 5-methylcytosine and some 5-halocytosine products which could potentially result in mistaken methylation at sites of inflammation. 4 These halogenated cytosine residues were not recognized by DNA repair enzymes suggesting the possibility of accumulation of heritable changes within the genome.Infection with Helicobacter pylori has been implicated in the development of gastric cancer with a relative risk increase of 2.2-to 6 fold when infection is detected. 5-8 The mechanism of cancer development in this setting has been attributed to inflammation leading to cell proliferation resulting in a propensity for gene mutation. Aberrant methylation due to H. pylori infection has been suggested as an additional mechanism bridging the gap between inflammation and cancer. In a series of 154 healthy volunteers and 72 patients with gastric cancer, methylation of 8 regions of 7 CpG islands was assessed. 14 Among the healthy volunteers, the extent of DNA methylation was 5.4-to 303-times higher in the H. pylori positive cases compared to the H. pylori negative cases (p<0.0001) suggesting an increase in methylation levels due to the presence of H. pylori. However, the comparison of methylation levels between healthy volunteers and patients with gastric cancer stratified by H. pylori status

show abstract

“…A recent study by Johnson-Maddux et al indicated that sampling and/or interpretive variance with ductal lavage specimens is not trivial. Only 48% of women producing atypical ductal lavage samples on the first attempt were found to have atypical samples on a subsequent attempt (15). Thus, the combination of sampling and interpretive variance with lavage is unlikely to be less than for RPFNA (18,19).…”

mentioning

confidence: 99%

Is There a Future for Ductal Lavage?

Fabian

2007

Clinical Cancer Research

View full text Add to dashboard Cite

Non-lesion-directed minimally invasive breast tissue sampling is currently used in the research setting both for risk stratification and for acquisition of material for response biomarkers in phase II chemoprevention trials. Prospective data linking morphology to eventual development of cancer are currently available only for nipple aspirate fluid harvest (NAF) and random periareolar fine needle aspiration (RPFNA). The finding of atypia with either of these two techniques increases relative risk to a level at least as great as that which would be expected with atypical hyperplasia in a diagnostic biopsy (1, 2). Both techniques improve risk predictions based on the widely used Gail model. NAF has been shown to improve discriminatory accuracy for average risk (3), and RPFNA improves discriminatory accuracy for high-risk (4) cohorts. The main drawback for NAF is that f15% to 50% of women do not produce it and, even if produced, NAF generally contains few epithelial cells (1, 5). Although RPFNA produces an evaluable cytomorphology specimen in more than 90% of high-risk women (2), if severe atypia is encountered, the location of the abnormality is uncertain. It was hoped that ductal lavage would overcome the drawbacks of both the NAF and RPFNA procedures. Ductal lavage might provide more cells and evaluable cytomorphology more frequently than NAF. The ability to identify and recannulate specific ducts would theoretically give ductal lavage an advantage over RPFNA by reducing sampling variance in prevention trials as well as providing a means of identifying the site of very abnormal cells if and when they are encountered.At first, the future seemed bright for ductal lavage. Dooley et al. (5) in a multicenter study reported that 60% of high-risk women presenting for breast tissue -based risk assessment were able to produce NAF, successfully underwent duct cannulation, and had evaluable epithelial cells in their ductal lavage specimen. Further, the median number of cells from evaluable specimens was increased from 120 with NAF to 4,000 to 13,500 with ductal lavage (5). Other investigators reported similar results (6, 7). Investigators highly skilled in this technique have reported that even non -NAF-producing ducts could be cannulated, and epithelial cells harvested (8 -10); however, a lavage is more likely to yield adequate cells if women undergoing this procedure produce NAF and are premenopausal (11,12). Based on these preliminary studies, an industry-sponsored trial was initiated in which women undergo ductal lavage at intervals and are then followed for the development of breast cancer.A study by Khan et al. (9) markedly diminished hope that ductal lavage might be used as a reliable early detection tool because the sensitivity of lavage in breasts known to have cancer was only 13% to 42%, depending on whether mild or severe atypia was used as the indicator lesion. This seeming paradox may be explained by the fact that not all cancers are associated with fluid production, nor do they all originate in ducts that empt...

show abstract

Reproducibility of cytologic atypia in repeat nipple duct lavage

Cited by 30 publications

References 34 publications

The Reliability of Nipple Aspirate and Ductal Lavage in Women at Increased Risk for Breast Cancer—a Potential Tool for Breast Cancer Risk Assessment and Biomarker Evaluation

The Reliability of Nipple Aspirate and Ductal Lavage in Women at Increased Risk for Breast Cancer—a Potential Tool for Breast Cancer Risk Assessment and Biomarker Evaluation

DNA Methylation: Its Role in Cancer Development and Therapy

Is There a Future for Ductal Lavage?

Contact Info

Product

Resources

About