Ductal Lavage: Risk Stratification Versus Cancer Detection

BMC Cancer, 2008

Past studies have shown that women with abnormal cytology or epithelial cells in nipple aspirate fluid (NAF) have an increased relative risk (RR) of breast cancer when compared to women from whom NAF was attempted but not obtained (non-yielders). This study analyzed NAF results from a group of women seen in a breast clinic between 1970-1991 (N = 2480). Our analysis presented here is an aggregate of two sub-groups: women with questionnaire data (n = 712) and those with NAF visits beginning in 1988 (n = 238), the year in which cancer case information was uniformly collected in California.

Cancer, 2002

B reast carcinoma arises in the epithelial cells lining the milk ducts and lobules that comprise the ductal system of the breast. 1,2 Ductal lavage is a minimally invasive office procedure performed on women who are considered to be at high risk for breast carcinoma to collect breast ductal epithelial cells for cytologic analysis to provide further risk stratification. The procedure involves the insertion of a microcatheter approximately 1.5 cm into a nipple orifice after topical anesthesia; lavaging the cannulated ductal system with normal saline; and analyzing the collected lavage effluent for the presence of normal, atypical, or malignant breast ductal cells.

BMC Women's Health, 2005

Background: Detection of cytologic atypia in nipple aspirate fluid (NAF) has been shown to be a predictor of risk for development of breast carcinoma. Manual collection of NAF for cytologic evaluation varies widely in terms of efficacy, ease of use, and patient acceptance. We investigated a new automated device for the non-invasive collection of NAF in the office setting.

American Journal of Epidemiology, 1992

This is a prospective study of breast cancer risk in relation to nipple aspirate fluid cytology in 2,701 volunteer white women from the San Francisco Bay Area first enrolled between 1973 and 1980. The women were not pregnant or lactating and were free of breast cancer within 6 months of entry into the study. The breast cancer status of this cohort was determined between June 1988 and April 1991. Follow-up was complete for 87% (n = 2,343) of the cohort, representing 29,961 person-years and an average of 12.7 years of follow-up. The overall breast cancer incidence was 4.4% (104 of 2,343) and rose with fluid cytology findings as follows: no fluid obtained, 2.6% (9 of 352); unsatisfactory specimen, 4.8% (15 of 315); normal cytology, 4.3% (56 of 1,291); epithelial hyperplasia, 5.5% (18 of 327); and atypical hyperplasia, 10.3% (6 of 58). Relative risks for breast cancer and their 95% confidence intervals were estimated by Cox regression, adjusting for age and year of entry. Compared with the relative risk for women who yielded no fluid, relative risks were: unsatisfactory specimen, relative risk (RR) = 1.4 (95% confidence interval (Cl) 0.6-3.3); normal cytology, RR = 1.8 (95% Cl 0.9-3.6); epithelial hyperplasia, RR = 2.5 (95% Cl 1.1-5.5); and atypical hyperplasia, RR = 4.9 (95% Cl 1.7-13.9). These findings were strongest for and were mainly confined to women aged 25-54 years. Women with atypical hyperplasia and a firstdegree family history of breast cancer were six times more likely to develop breast cancer than were women with atypical hyperplasia but without a family history of breast cancer (95% Cl 1.0-30.2). These findings provide strong support for our hypothesis that hyperplasia and atypical hyperplasia diagnosed in nipple aspirates of breast fluid are associated with an increased risk of breast cancer.

British Journal of Cancer, 1999

We previously demonstrated that nipple aspirate fluid (NAF) can be obtained from virtually all non-Asian women between the ages of 30 and 72. The focus of this report is to (1) determine the association of candidate markers of breast cancer risk in NAF obtained from fresh mastectomy specimens with residual breast carcinoma, and (2) evaluate the association of the markers

British Journal of Cancer, 1997

To evaluate the feasibility of nipple aspiration and to identify intermediate markers of breast cancer risk, nipple aspirate fluid (NAF) was collected from 177 subjects using a modified breast pump. The first 33 subjects demonstrated that we could obtain NAF quickly, reliably and repeatedly. Specimens from the remaining 144 subjects were collected to evaluate promising cellular biomarkers. NAF was obtained in 167 out of 177 (94%) subjects overall and in 99% of the 144 most recent subjects. Sufficient NAF was obtained to evaluate cytology in 160 out of 167 (96%) cases and specimens were sufficiently cellular to analyse DNA markers in 53% of cases. Among the last 144 subjects, menopausal status did not influence the ability to obtain NAF. NAF cytology correlated with increased breast cancer risk (P = 0.002). Using computerized image analysis of NAF epithelial cells, DNA index (P = 0.0002), percentage of cells in G2M (P = 0.05) and percentage of cells with hypertetraploidy (P = 0.002) increased as cytology became more abnormal. Our data indicate that NAF can be obtained in essentially all eligible subjects; that breast epithelial cells are evaluable in > 95% of NAF samples for cytology and in over half of NAF samples for DNA index (ploidy) and cell cycle analysis; and that abnormal NAF cytology correlates with increased breast cancer risk. This suggests that biomarkers identified in nipple aspirate fluid may prove useful either as an adjunct to currently accepted breast cancer screening methods, or to evaluate response to a chemopreventive agent.

BMC Cancer

Background Nipple fluid aspiration (NFA) is a technique to acquire nipple aspirate fluid (NAF), which is considered a rich source of breast-specific biomarkers. Originating directly from the mammary ducts, this liquid biopsy can offer insight into the process of carcinogenesis at its earliest stage and therefore could be of added value to the current imaging-based breast cancer screening tools. With that in mind, it is necessary to know how well NFA is tolerated. Aim To evaluate the participants’ tolerability of NFA compared to breast imaging screening methods and blood draws. Materials and methods Three cohorts of women underwent NFA: healthy women (n = 190), women diagnosed with breast cancer (n = 137) and women at high risk of developing breast cancer (n = 48). A 0–10 discomfort score of NFA, mammography, breast MRI and blood draws, was filled in at the study visits, which took place once or annually. Results The median discomfort rate of NFA was 1, which was significantly lower ...

Clinical Breast Cancer, 2002

Two related techniques of breast epithelial sampling have emerged in the past several years: ductal lavage, in which fluid-yielding nipple ducts are cannulated at their orifices and lavaged with saline while the breast is intermittently massaged; and ductoscopy, in which discharging or fluid-yielding duct orifices are dilated, intubated with a microendoscope, and the lumen directly visualized. Both of these techniques have significant potential in terms of allowing the repeated sampling of ductal epithelium over time and, as such, have generated considerable enthusiasm. However, data regarding the impact of these techniques on the detection of significant breast disease is very scant. It is important at the outset of the assessment of this new technology that breast cancer clinicians and clinical researchers think carefully about the standards of evidence that need to be met regarding the benefits of these procedures before they are widely adopted. In this review of the rationale and early results of these procedures, we attempt to define some of these evidentiary requirements.

Therapy, 2006

Advances in Bioscience and Biotechnology, 2013

Background: The ability to identify asymptomatic women at high risk for breast cancer using known pre-malignant changes in exfoliative cytopathology of nipple aspirate fluid is of clinical importance. Exfoliative cytopathology of Nipple Aspirate Fluid (NAF) has been shown to be an important adjunct to the currently accepted standard of medical care, i.e. mammography, coupled with physical examination, for the diagnosis of breast cancer. This is especially important for the subset of women aged 18-50 who are not identified as "high risk", and therefore, for whom mammography is not routinely recommended. The objective of this study was to determine if a new, patented Class II medical device, the Mammary Aspirate Specimen Cytology Test (MASCT) System, designed to collect NAF for subsequent cytological examination is safe and effective. Methods: The MASCT medical device is a modified breast pump and was used to obtain bilateral specimens from 34 healthy, non-pregnant, female subjects for cytopathological examination. A conventional breast disease work-up was performed (medical history/risk factor collection, clinical breast examination and mammogram) and NAF specimens were collected. Specimen weight was measured and a cytopathological examination was performed. Vital signs measurements, clinical laboratory analysis, and adverse event reporting were performed. Results: Based on cytopathological evaluation and/or measurable weight changes on the specimen collection membrane filter, all breasts evaluated (100%) yielded nipple aspirate fluid. Specimen weights ranged from <1 to 37 mg and all specimens evaluated cytopathologically were deemed to be clinically useful. One patient's specimen was not available for cytopathological examination due to specimen mishandling, resulting in 60 breasts (representing 30 subjects) being evaluated cytologically. Fifty-eight of sixty breasts evaluated cytopathologically (97%) were reported as cytology Class I, and 2 of 60 (3%) were reported as cytology Class IIa. Cytopathological findings correlated well with mammogram and clinical breast exam results. No adverse events, including pain from the collection procedure, were reported. Conclusion: Based on this clinical study, we conclude that the Mammary Aspiration Specimen Cytology Test device is safe and effective for the collection of mammary aspirate specimens for laboratory cytopathological testing.