Nipple Aspirate Fluid Cytology Research Articles

Nipple Aspirate Fluid Cytology in the Office-Based Screening for Breast Cancer Risk [333

Nipple Aspirate Fluid Cytology in the Office-Based Screening for Breast Cancer Risk [333

Nipple aspirate fluid and ductoscopy to detect breast cancer

We prospectively performed cytologic assessment and image analysis (IA) on matched nipple aspirate fluid (NAF) and mammary ductoscopy (MD) specimens to determine (1) the accuracy of these methods in cancer detection and (2) whether the two collection methods provide complementary information.NAF and MD specimens were collected from 84 breasts from 75 women (nine bilateral samples) who underwent breast surgery. Cytologic evaluation was performed on all samples. IA was performed on slides with sufficient epithelial cells.Cytologic evaluation proved more accurate in patients without pathologic spontaneous nipple discharge (PND) than those with PND, mainly because of the potential false positive diagnosis in the latter. While the sensitivity of NAF and MD cytology was low (10% and 14%, respectively), both were 100% specific in cancer detection in the non-PND cohort. Combining NAF and MD cytology information improved sensitivity (24%) without sacrificing specificity. Similar to cytology, IA was more accurate in patients without PND having high specificity (100% for aneuploid IA), but relatively low sensitivity (36%). Combining NAF and MD cytology with aneuploid IA improved the sensitivity (45%) while maintaining high specificity (100%). The best predictive model was positive NAF cytology and/or MD cytology combined with IA aneuploidy, which resulted in 55% sensitivity and 100% specificity in breast cancer detection.Cytologic evaluation and IA of NAF and MD specimens are complementary. The presence of atypical cells arising from an intraductal papilloma in ductoscopic specimens is a potential source of false positive diagnosis in patients with nipple discharge.

Epithelial cells in nipple aspirate fluid and subsequent breast cancer risk: A historic prospective study

BackgroundPast 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.MethodsCytological classification was determined for a group of 946 women using the most abnormal epithelial cytology observed in fluid specimens. Breast cancer incidence and mortality status was determined through June 2006 using data from the California Cancer Registry, California Vital Statistics and self-report. We estimated odd ratios (ORs) for breast cancer using logistic regression analysis, adjusting for age. We analyzed breast cancer risk related to abnormality of NAF cytology using non-yielders as the referent group and breast cancer risk related to the presence or absence of epithelial cells in NAF, using non-yielders/fluid without epithelial cells as the referent group.ResultsOverall, 10% (93) of the 946 women developed breast cancer during the follow-up period. Age-adjusted ORs and 95% confidence intervals (C.I.) compared to non-yielders were 1.4 (0.3 to 6.4), 1.7 (0.9 to 3.5), and 2.0 (1.1 to 3.6) for women with fluid without epithelial cells, normal epithelial cells and hyperplasia/atypia, respectively. Comparing the presence or absence of epithelial cells in NAF, women with epithelial cells present in NAF were more likely to develop breast cancer than non-yielders or women with fluid without epithelial cells (RR = 1.9, 1.2 to 3.1).ConclusionThese results support previous findings that 1) women with abnormal epithelial cells in NAF have an increased risk of breast cancer when compared to non-yielders or women with normal epithelial cells in NAF and 2) women with epithelial cells present in NAF have an increased risk of breast cancer when compared to non-yielders or women who had NAF without epithelial cells present.

Prospective multicenter trial to determine the feasibility of collection and predictive ability of breast fluid analysis in postmenopausal women receiving SERMs

We conducted a prospective ancillary study to the study of tamoxifen and raloxifene (STAR) trial involving 4 institutions to determine: (1) our ability to collect nipple aspirate fluid (NAF) in postmenopausal women taking medication to decrease breast proliferation and (2) NAF biomarkers associated with breast cancer. NAF was collected before and 6 months after starting treatment. Three biomarkers, cytology, fluid volume, and prostate-specific antigen (PSA), were analyzed. NAF was collected from 26 of 33 (79%) enrolled subjects at baseline. We were able to collect fluid in 84% of the subjects who produced NAF at baseline and returned for second aspiration after 6 months of treatment. In these women, cytology was unchanged in 85%, improved in 11%, and worsened in 4% of breasts. Median PSA increased from 37.5 to 112 ng/L after treatment. NAF volume did not significantly change. In conclusion, after treatment with tamoxifen or raloxifene, changes in both NAF cytology and PSA were generally favorable, consistent with their expected antiproliferative effective effect on the breast. Multiinstitutional clinical trials in postmenopausal women using NAF biomarkers as the primary endpoints are feasible.

Biologic markers of breast cancer in nipple aspirate fluid and nipple discharge are associated with clinical findings

Background: The aim of this prospective study was to assess predictive markers in nipple aspirate fluid (NAF) and pathologic nipple discharge (PND) collected prior to excisional breast biopsy, as well as clinical factors available prior to biopsy, with histopathologic results in women with a radiographically suspicious and/or palpable breast lesion. Methods: 208 NAF samples from 191 women were evaluated for the following candidate predictive proteins and cellular markers: prostate-specific antigen (PSA), human glandular kallikrein 2 (hK2), basic fibroblast growth factor (bFGF), S phase fraction (SPF), DNA index, and cytology. Clinical factors included whether or not the lesion was palpable, menopausal status, history of pregnancy, history of birth control or hormone replacement use, and PND. Results: Considering all women, bFGF ( p = 0.005) and SPF (0.031) were associated, and abnormal cytology approached an association ( p = 0.056) with the presence of breast cancer. Women with PND were less likely to have breast cancer (4 vs. 37%, p < 0.001) or palpable lesions (10 vs.43%, p < 0.001), were younger, had lower PSA levels ( p = 0.046), and were more likely to have atypical NAF cytology ( p = 0.002). Excluding PND, increased age, postmenopause (both p < 0.01), high bFGF ( p = 0.004) and low PSA ( p = 0.05) were associated with cancer. The best breast cancer predictive model included cytology, bFGF, and age (88% sensitive and 57% specific). When the data were divided by menopausal status, the optimal models to predict breast cancer, which included NAF hK2 or PSA and age, were 100% sensitive and 41% specific in pre- vs. 93% sensitive and 12% specific in postmenopausal women. Conclusion: NAF and clinical biomarkers are sensitive predictors of whether a breast contains cancer, and may ultimately help guide treatment. Future studies to determine the optimal combination of predictive markers are warranted.

Nipple Aspirate Fluid Cytology and the Gail Model for Breast Cancer Risk Assessment in a Screening Population

Nipple Aspirate Fluid Cytology and the Gail Model for Breast Cancer Risk Assessment in a Screening Population

Nipple Aspirate Fluid Cytology and the Gail Model for Breast Cancer Risk Assessment in a Screening Population

Recent guidelines suggest that chemoprevention with tamoxifen may be appropriate for women who have a 5-year risk of breast cancer greater than 1.66% calculated using the Gail model. To determine whether nipple aspirate fluid (NAF) cytology combined with the Gail model provides breast cancer risk assessment that is superior to either method alone. Prospective observational cohort of 6,904 asymptomatic women. Breast cancer cases were identified through follow-up with the women and linkage to cancer registries. We used proportional hazards modeling to recalculate the coefficients for the predictor variables used in the Gail model. NAF cytology was added to create a second model. The two models were compared using the concordance statistic (c-statistic). During 14.6 years of follow-up, 400 women were diagnosed with breast cancer. There were 940 (14%) women with hyperplasia and 109 (1.6%) women with atypical hyperplasia found in NAF. Adding NAF cytology results to the Gail model significantly improved the model fit (P < 0.0001). The c-statistic for the Gail model was 0.62, indicating only modest discriminatory accuracy. Adding NAF cytology to the model increased the c-statistic to 0.64. NAF cytology results had the largest effect on discriminatory accuracy among women in the upper third of Gail model risk. The relative incidence for the highest quintile of risk score compared with the lowest quintile was 7.2 for the Gail model and 8.0 for the model including NAF cytology. NAF cytology has the potential to improve prediction models of breast cancer incidence, particularly for high-risk women.

Multiple Sampling for Increasing the Diagnostic Sensitivity of Nipple Aspirate Fluid for Atypical Cytology

To determine if repeated collection of nipple aspirate fluid (NAF) can improve the diagnostic sensitivity for cytologic atypia, a marker of increased risk of breast cancer.Two hundred sixty-seven women without known breast disease volunteered for NAF cytology at 5 6-month intervals over 2 years. NAF samples were prepared on Millipore filters (Millipore Filter Corp., Bedford, Massachusetts, U.S.A.) and stained with a modified Papanicolaou method. Fluid availability and cellular abnormalities were evaluated for each collection attempt. Cellular findings were classified as benign, hyperplasia or atypia.NAF was obtained from 178 women (66.6%) at the first visit and from an additional 15, 10, 2 and 4 women at visits 2, 3, 4 and 5, respectively, for a cumulative total of 78.2% by visit 5. The number of women yielding NAF containing hyperplastic or atypical epithelial cells was determined at each visit. Hyperplastic cells were found in 34 (19.1%) at visit 1 and in an additional 20, 10, 5 and 4 women at visits 2, 3, 4 and 5, respectively. Atypical epithelial cells were present in 12 (6.7%) women at the initial visit and in an additional 11, 7, 5 and 1 women at visits 2, 3, 4 and 5, respectively, for a cumulative percent of 18.2 at visit 5. NAF could not be obtained from 58 women at any visit.These findings suggest that an optimum collection method for NAF cytology should consist of at least 3 or 4 separate fluid aspiration attempts. Reviewing repeated multiple samples instead of 1 increases the number of women who can be evaluated and the likelihood of detecting cytologic atypia.

Nipple aspirate fluid cytology in breast carcinoma.

Nipple aspirate fluid (NAF) cytology is a simple noninvasive method to study cells exfoliated into the ductal system of the breast. In the current study, the significance of cytologic findings in NAF was determined by correlating them with histopathologic findings from corresponding breast tissue. Cytologic-histologic correlations of NAF were performed in only a few studies. Nipple aspirate fluid was collected by breast massaging and by using a breast aspiration device from 74 women with biopsy confirmed intraductal or invasive carcinoma with or without a history of preoperative neoadjuvant chemotherapy. Cytospin preparations were Pap stained. The number of epithelial cells was quantitated and foamy macrophages were semiquantitatively scored. Cytologic findings were categorized as insufficient for diagnosis (less than 10 epithelial cells), benign, mild atypia, marked atypia or suspicious, and malignant. Finally, they were correlated with tissue findings. Nipple aspirate fluid was obtained from 74 women, including 24 who had received preoperative neoadjuvant chemotherapy. The median age of patients was 54 years. A mean volume of 57 microL NAF and a mean of 149 epithelial cells were obtained. Foamy macrophages were present in 51 (70%) of the specimens. There was a significant correlation between the presence of epithelial cells and foamy macrophages (P < 0.001). Patients treated with chemotherapy had fewer epithelial cells in their NAF compared with patients who were not treated with chemotherapy. Thirty specimens (41%) were inadequate for diagnosis, 34 were (46%) benign, 5 (7%) were mildly atypical, 1 (1%) was markedly atypical, and 4 (5%) were malignant. Of the five cases with mildly atypical cytology, three were intraductal papilloma, one was low-grade papillary intraductal carcinoma, and one was low-grade intracystic papillary carcinoma with invasion in the corresponding tissue specimen. The single case with markedly atypical NAF cytology had extensive ductal carcinoma in situ (DCIS). Of the four cases with malignant NAF cytology, two were extensive DCIS and two had invasive carcinoma with extensive DCIS in the breast specimen. Overall, 3 (27%) of 11 cases of DCIS were detected in NAF and only 2 (4%) of 52 invasive carcinomas including the only two cases with extensive DCIS were detected in NAF. The probability of detecting malignant cells in NAF is dependent on the extent of DCIS and nipple involvement by DCIS. Nipple aspirate fluid is not a sensitive test for detecting invasive carcinoma of the breast. Atypical cytology in NAF is associated with papillary lesions in the underlying breast.

Biological markers of risk in nipple aspirate fluid are associated with residual cancer and tumour size.

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 with breast tumour progression. Nipple aspiration was performed on 97 specimens. Cytology, DNA index (including % hypertetraploid cells), cell cycle parameters (S phase fraction, % cells in G2/M), prostate-specific antigen (PSA), epidermal growth factor (EGF), testosterone, carcinoembryonic antigen (CEA) and prostaglandin D synthase (PGDS) were evaluated in NAF for their association with (1) residual ductal carcinoma in situ (DCIS) or invasive cancer, and (2) pathologic tumour size. NAF was obtained from 99% (96/97) of specimens. Atypical and malignant NAF cytology were significantly associated with residual DCIS or invasive cancer (P = 0.001) and with larger tumours (P = 0.004). One hundred per cent and 88% of subjects with malignant and atypical NAF cytology, respectively, had residual carcinoma. The percentage of cells in G2/M and DNA index were associated both with risk of residual carcinoma (P = 0.01 for each) and larger tumour size (DNA index, P = 0.03; G2/M, P = 0.05), although neither biomarker improved the ability of NAF cytology, to predict residual breast cancer. Higher DNA index was associated with atypical cytology (P = 0.0001). In summary, atypical and malignant NAF cytology are associated with larger tumour size, and are highly predictive of residual carcinoma after needle or excisional biopsy of the breast. © 1999 Cancer Research Campaign

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

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.