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PubMedDate not supplied

Multiple sampling for increasing the diagnostic sensitivity of nipple aspirate fluid for atypical cytology.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Adult↗
PubMed1979

Early detection of ductal breast cancer: the diagnostic procedure for pathological discharge from the nipple.

Pathologic discharge from the nipple may be the only symptom of an early stage of carcinoma. Galactography is then the diagnostic method of choice to locate intraductal, nonpalpable lesions. The technique of galactography, the adequate surgical approach of pathologic galactographs (milk-duct segment resection), and the appropriate histological work-up of the surgical specimen are demonstrated. We report on 1918 galactographies in 1363 women with pathological discharge. In only 427 cases was a milk duct segment resection necessary (31.4%). In 8.5%, we found invasive intraductal cancer and in 2.9% ductal carcinomata in situ. Only 1 patient with breast cancer had axillary metastases. Extensive intraductal solid, papillary or adenomatous proliferations were found in 11.9% of the patients with excision. In 46.7% of the patients, papillomas were excised, a definitive treatment for this process. The supposition for success in the early diagnosis of cancer is close teamwork among the radiology, surgery and pathology services: the diagnostic result depends upon this. We attribute our yield of exact diagnosis to a very sophisticated histological work-up. We believe that this is necessary to avoid diagnostic failures.

Biopsy↗
PubMed1991

Malignant melanoma of the nipple: a case studied with radiolabeled monoclonal antibody.

We describe a case of histologically confirmed malignant melanoma of the nipple. The rare occurrence of these lesions accounts for the relative lack of criteria for standard surgical treatment. After a conventional workup including mammography, chest X ray, bone scan, liver ultrasonography and cytologic smear of the lesion, we used specific radiolabeled monoclonal antibody and external photoscanning to differentiate melanoma from Paget's disease. The patient underwent wide local excision of the lesion and axillary node dissection, and tumor control is optimal since she has no evidence of disease after 5 years of follow-up.

Antibodies, Monoclonal↗
PubMed1993

Treatment of inverted nipples using a disposable syringe.

Seven mothers who had inverted nipples were helped to breastfeed their infants with the assistance of a simple device made from a 10 ml disposable syringe. These women were able to successfully breastfeed within one week. On follow-up, these mothers were able to sustain adequate breastfeeding.

Breast Feeding↗
PubMed1994

Ultrastructural visualization and neurochemical characterization of spinal projections of primary sensory afferents from the nipple: combined use of transganglionic transport of HRP-WGA and glutamate immunocytochemistry.

We used transganglionic transport of the neuronal tracer horseradish peroxidase coupled to wheat germ agglutinin (HRP-WGA) and post-embedding immunogold staining to determine the spinal projections and neurochemical identity of sensory afferents originating from a discrete cutaneous area. After SC injection of tracer into the nipple of lactating rats and reaction with tetramethylbenzidine stabilized with diaminobenzidene (TMB-DAB) or DAB and cobalt (TMB-DAB-Co), we found labeled terminals in the internal part of the first two layers of the dorsal horn where they formed axodendritic synapses and, at times, central elements of glomeruli, synaptic complexes believed to be involved in the integration of sensory messages. Immunogold staining of ultra-thin sections of tissue reacted with TMB-DAB-Co revealed that many mammary afferents contained glutamate as putative neurotransmitter. This combined approach thus offers the possibility of marking a limited set of primary afferents, after capture of tracer by sensory receptors of restricted peripheral areas, to visualize their projections at the spinal level and to determine their neurochemical nature with electron microscopy.

Animals↗
PubMed2006

Celecoxib decreases prostaglandin E2 concentrations in nipple aspirate fluid from high risk postmenopausal women and women with breast cancer.

BACKGROUND: Celecoxib inhibits PGE2 production in cancerous tissue. We previously reported that PGE2 levels in nipple aspirate fluid (NAF) and plasma were not decreased in women at increased breast cancer risk who received celecoxib 200 mg twice daily (bid). The endpoints of the current study were to determine if a short course of celecoxib 400 mg bid would decrease PGE2 levels in women 1) at increased breast cancer risk, and 2) with established breast cancer. METHODS: NAF and plasma samples were collected before, 2 weeks after taking celecoxib 400 mg bid, and two weeks after washout from 26 women who were at increased breast cancer risk. From 13 women with newly diagnosed breast cancer, NAF from the incident breast and plasma were collected before and on average 2 weeks after taking celecoxib. Additionally, in nine of the 13 women with breast cancer, NAF was collected from the contralateral breast. RESULTS: No consistent change in NAF or plasma PGE2 levels was noted in high risk premenopausal women. NAF PGE2 levels decreased after celecoxib administration in postmenopausal high risk women (p = 0.02), and in both the NAF (p = 0.02) and plasma (p = 0.03) of women with breast cancer. CONCLUSION: Celecoxib 400 mg bid taken on average for 2 weeks significantly decreased NAF, but not plasma, PGE2 levels in postmenopausal high risk women, and decreased both NAF and plasma PGE2 levels in women with newly diagnosed breast cancer. PGE2 levels may predict celecoxib breast cancer prevention and treatment efficacy. Our observations are preliminary, and larger studies to confirm and extend these findings are warranted.

Adolescent↗
PubMed2006

Proteomic analysis of nipple aspirate fluid from women with early-stage breast cancer using isotope-coded affinity tags and tandem mass spectrometry reveals differential expression of vitamin D binding protein.

BACKGROUND: Isotope-coded affinity tag (ICAT) tandem mass spectrometry (MS) allows for qualitative and quantitative analysis of paired protein samples. We sought to determine whether ICAT technology could quantify and identify differential expression of tumor-specific proteins in nipple aspirate fluid (NAF) from the tumor-bearing and contralateral disease-free breasts of patients with unilateral early-stage breast cancer. METHODS: Paired NAF samples from 18 women with stage I or II unilateral invasive breast carcinoma and 4 healthy volunteers were analyzed using ICAT labeling, sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE), liquid chromatography, and MS. Proteins were identified by sequence database analysis. Western blot analysis of NAF from an independent sample set from 12 women (8 with early-stage breast cancer and 4 healthy volunteers) was also performed. RESULTS: 353 peptides were identified from tandem mass spectra and matched to peptide sequences in the National Center for Biotechnology Information database. Equal numbers of peptides were up- versus down-regulated. Alpha2HS-glycoprotein [Heavy:Light (H:L) ratio 0.63] was underexpressed in NAF from tumor-bearing breasts, while lipophilin B (H:L ratio 1.42), beta-globin (H:L ratio 1.98), hemopexin (H:L ratio 1.73), and vitamin D-binding protein precursor (H:L ratio 1.82) were overexpressed. Western blot analysis of pooled samples of NAF from healthy volunteers versus NAF from women with breast cancer confirmed the overexpression of vitamin D-binding protein in tumor-bearing breasts. CONCLUSION: ICAT tandem MS was able to identify and quantify differences in specific protein expression between NAF samples from tumor-bearing and disease-free breasts. Proteomic screening techniques using ICAT and NAF may be used to find markers for diagnosis of breast cancer.

Biomarkers, Tumor↗
PubMed2005

Nipple aspiration and ductal lavage in women with a germline BRCA1 or BRCA2 mutation.

INTRODUCTION: The aim of this study was to collect serial samples of nipple aspirate (NA) and ductal lavage (DL) fluid from women with germline BRCA1/2 mutations in order to create a biorepository for use in identifying biomarkers of breast cancer risk. METHODS: Between March 2003 and February 2005, 52 women with germline BRCA1 or BRCA2 mutations (median age 43 years, range 27 to 65 years) were scheduled for six-monthly NA, DL and venesection. DL was attempted for all NA fluid-yielding (FY) and any non-FY ducts that could be located at each visit. RESULTS: Twenty-seven (52%) women were postmenopausal, predominantly (19/27) from risk reducing bilateral salpingo-oophorectomy (BSO). FY ducts were identified in 60% of all women, 76% of premenopausal women versus 44% of postmenopausal (P = 0.026). Eighty-five percent of women had successful DL. Success was most likely in women with FY ducts (FY 94% versus non-FY 71% (P = 0.049). DL samples were more likely to be cellular if collected from FY ducts (FY 68% versus non-FY 43%; P = 0.037). Total cell counts were associated with FY status (FY median cell count 30,996, range 0 to >1,000,000 versus non-FY median cell count 0, range 0 to 173,577; P = 0.002). Four women (8%) had ducts with severe atypia with or without additional ducts with mild epithelial atypia; seven others had ducts with mild atypia alone (11/52 (21%) in total). Median total cell count was greater from ducts with atypia (105,870, range 1920 to >1,000,000) than those with no atypia (174, 0 to >1,000,000; P <or= 0.001). CONCLUSION: It is feasible to collect serial NA and DL samples from women at high genetic risk of breast cancer, and we are creating a unique, prospective collection of ductal samples that have the potential to be used for discovery of biomarkers of breast cancer risk and evaluate the ongoing effects of risk reducing BSO. DL cellular atypia was not predictive of a current breast cancer and longer follow up is needed to determine whether atypia is an additional marker of future breast cancer risk in this population already at high genetic risk of breast cancer.

Adult↗
PubMed2004

Comparison of hormone levels in nipple aspirate fluid of pre- and postmenopausal women: effect of oral contraceptives and hormone replacement.

The effects of ovarian suppression by oral contraceptives as well as hormone replacement therapy were studied on hormone levels and on products of hormone action in nipple aspirate fluid (NAF) from breasts of pre- and postmenopausal women. Multiple samples per subject revealed high consistency (intraclass correlation coefficients) for all products measured. Compared with premenopausal women, NAF progesterone was much lower in postmenopausal women, but NAF androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate concentrations were not different. With oral contraceptive use, estradiol, estrone sulfate, and progesterone levels were similarly lower in serum and NAF. In postmenopausal women, NAF estradiol and estrone sulfate were not significantly less than those in premenopausal women, nor were epidermal growth factor or cathepsin D levels, but IL-6 was elevated. Despite corresponding changes in hormones in serum and NAF over time, correlations based on simultaneous sampling were not significant. It is concluded that: 1) potential precursors of estradiol remain at comparable levels in the breast after menopause; 2) local synthesis is important for maintenance of estradiol levels in NAF of postmenopausal women but less important for progesterone; and 3) changes in the serum parameters are accurately reflected in NAF, but only after a matter of days. These findings provide additional validation for the physiological relevance of NAF hormone levels as potential breast cancer risk markers.

Adult↗
PubMed2003

Nipple aspirate fluid expression of urokinase-type plasminogen activator, plasminogen activator inhibitor-1, and urokinase-type plasminogen activator receptor predicts breast cancer diagnosis and advanced disease.

BACKGROUND: Tumor expression of urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and uPA receptor (uPAR) are breast cancer prognostic factors. Less is known about their usefulness in breast cancer diagnosis. Nipple aspirate fluid (NAF) is secreted into the breast duct and collected noninvasively, making it potentially useful both in breast cancer diagnosis and prognosis. We determined the association of uPA, PAI-1, and uPAR levels in NAF with breast cancer (1) detection and (2) advanced disease. METHODS: A total of 88 NAF specimens were collected from women with or without breast cancer, and uPA, PAI-1, and uPAR expression were measured by enzyme-linked immunosorbent assay. RESULTS: uPA and uPAR were independent predictors of cancer presence; uPAR was also an independent predictor of advanced disease stage. Higher PAI-1 expression in breast cancer that was found with univariate analysis was not observed after logistic regression was applied. CONCLUSIONS: NAF evaluation of uPA, uPAR, and, perhaps, PAI-1 (significant only in univariate analysis) may provide useful breast cancer diagnostic and prognostic information.

Adult↗
PubMed2002

Circulating testosterone and prostate-specific antigen in nipple aspirate fluid and tissue are associated with breast cancer.

Preliminary evidence has associated testosterone and prostate-specific antigen (PSA) with breast cancer. Our objective was to determine whether a) testosterone levels in nipple aspirate fluid (NAF), serum, or breast tissue are associated with breast cancer; b) testosterone levels in serum are associated with levels in NAF; c) PSA in NAF, serum, or breast tissue is associated with breast cancer; and d) serum PSA is associated with NAF PSA levels. We obtained 342 NAF specimens from 171 women by means of a modified breast pump. Additionally, we collected 201 blood samples from 99 women and 51 tissue samples from 41 subjects who underwent surgical resection for suspected disease. Women currently using birth control pills or hormone replacement therapy were excluded from the study. Controlling for age and menopausal status, serum testosterone was significantly increased in women with breast cancer (p = 0.002). NAF and serum testosterone levels were not associated. Neither NAF nor tissue testosterone was associated with breast cancer. Controlling for menopausal status and age, NAF PSA was significantly decreased in women with breast cancer (p < 0.001). We did not find serum PSA to be associated with breast cancer, although we found an indication that, in postmenopausal women, its levels were lower in women with cancer. Serum PSA was associated with NAF PSA in postmenopausal women (p < 0.001). PSA levels in cancerous tissue were significantly lower than in benign breast specimens from subjects without cancer (p = 0.011), whereas levels of PSA in histologically benign specimens from subjects with cancer were intermediate. Our results suggest that serum testosterone is increased and NAF PSA is decreased in women with breast cancer, with PSA expression being higher in normal than in cancerous breast tissues. NAF and serum PSA levels in postmenopausal women are correlated, suggesting that as laboratory assessment of PSA becomes more sensitive, serum PSA may become useful in identifying women with breast cancer.

Adult↗
PubMed2003

Quality control and peak finding for proteomics data collected from nipple aspirate fluid by surface-enhanced laser desorption and ionization.

BACKGROUND: Recently, researchers have been using mass spectroscopy to study cancer. For use of proteomics spectra in a clinical setting, stringent quality-control procedures will be needed. METHODS: We pooled samples of nipple aspirate fluid from healthy breasts and breasts with cancer to prepare a control sample. Aliquots of the control sample were used on two spots on each of three IMAC ProteinChip arrays (Ciphergen Biosystems, Inc.) on 4 successive days to generate 24 SELDI spectra. In 36 subsequent experiments, the control sample was applied to two spots of each ProteinChip array, and the resulting spectra were analyzed to determine how closely they agreed with the original 24 spectra. RESULTS: We describe novel algorithms that (a) locate peaks in unprocessed proteomics spectra and (b) iteratively combine peak detection with baseline correction. These algorithms detected approximately 200 peaks per spectrum, 68 of which are detected in all 24 original spectra. The peaks were highly correlated across samples. Moreover, we could explain 80% of the variance, using only six principal components. Using a criterion that rejects a chip if the Mahalanobis distance from both control spectra to the center of the six-dimensional principal component space exceeds the 95% confidence limit threshold, we rejected 5 of the 36 chips. CONCLUSIONS: Mahalanobis distance in principal component space provides a method for assessing the reproducibility of proteomics spectra that is robust, effective, easily computed, and statistically sound.

Algorithms↗
PubMed2005

Breast lesions causing nipple discharge: preoperative galactography-aided stereotactic wire localization.

OBJECTIVE: Lesions that present with nipple discharge typically are not visible on mammography or sonography but can be detected on galactography. Therefore, the usual methods for preoperative localization (wire placement under sonography or stereotactic guidance) are not applicable. We report our preliminary experience of galactography-aided stereotactic wire (n = 8) or coil (n = 1) localization of small intraductal lesions. CONCLUSION: Galactography-aided wire or coil localization is a practical localization method for intraductal lesions not detectable on mammography or sonography.

Adult↗
PubMed2006

Non-palpable and non-invasive ductal carcinoma with bloody nipple discharge successfully resected after cancer spread was accurately diagnosed with three-dimensional computed tomography and galactography.

A case of ductal carcinoma in situ (DCIS) that was treated by partial mastectomy is reported. The operation was performed after accurate estimation of cancer spread by three-dimensional computed tomography (3D-CT). The patient was a 39-year-old woman without a palpable lump who had a bloody nipple discharge. Ultrasonography showed distended mammary ducts with intraductal components. Fine needle aspiration cytology revealed ductal carcinoma. Galactography showed two subsegmental ducts and peripheral branches in the upper-inner quadrant of the right breast. 3D-CT depicted a well enhanced segmental-clumped lesion including two subsegments of a duct lobular system shown in galactograms. DCIS was diagnosed and partial mastectomy following the video assisted thoracoscopic surgery (VATS) marker insertion was performed, after cancer spread was accurately diagnosed by 3D-CT guidance. DCIS resected by minimally sufficient partial mastectomy with negative surgical margins was diagnosed histopathologically.

Adult↗
PubMed2006

Multi-volume fusion imaging of MR ductography and MR mammography for patients with nipple discharge.

Because nipple discharge is caused by carcinoma as well as benign disease, identification of intraductal abnormalities with ductography is important. Ductography is an invasive mammographic examination in which contrast material is injected directly into the duct. Failure to cannulate or extravasation may occur. Ductography shows evidence of lesions, such as filling defects, duct obstruction, or wall irregularity, but it does not reveal the lesion itself. Furthermore, ductography produces a two-dimensional image, so it does not show the shape of the dilated duct or the precise location of the intraductal lesion in the breast. We applied three-dimensional (3D) heavily T2-weighted imaging with fat suppression of the breast to produce MR ductography. The dilated ducts are seen in 3D as tubular structures with high signal, and intraductal abnormalities are seen as signal defects. Furthermore, MR ductography can show an obstructed duct that cannot be seen on ductography. We also performed 3D breast MRI with the intravenous infusion of contrast material to show the lesion itself. Finally, we fused these 2 volume images into a single 3D fused image that not only shows the existence of intraductal abnormality, but reveals the shape, size, and extent of lesion, allowing us to understand easily the relationship between the ducts with dilation and any intraductal lesions in the breast. We herein introduce and describe this noninvasive method and discuss various factors related to its diagnostic use.

Breast Neoplasms↗
PubMed2005

Paget's disease of the nipple as local recurrence after breast-conservation treatment for early-stage breast cancer.

Breast conservation treatment (BCT) for early-stage breast cancer is associated with survival rates comparable with mastectomy but has the risk of ipsilateral breast tumor recurrence, including Paget's disease of the nipple. A small number of cases of Paget's disease presenting as local recurrence following BCT for breast cancer have been previously reported. Between 1977 and 2002, 2181 women with early-stage breast cancer were treated with BCT at the Hospital of the University of Pennsylvania. In this cohort, there were 183 local treatment failures, 4 of which were cases of Paget's disease (2.2%), which are reported herein. These local recurrences developed 1.8, 3.8, 7.3, and 9.7 years after diagnosis of the patients' primary tumors. Three of the 4 primary cancers were invasive ductal carcinomas, with an associated intraductal component, and 1 was ductal carcinoma in situ. All 4 patients were successfully given salvage therapy consisting of mastectomy with or without tamoxifen, with follow-up times of 20.9, 10.6, 3.1, and 3.8 years. Paget's disease as local recurrence after BCT is uncommon and can be treated with salvage therapy if detected early.

Aged↗
PubMed2002

Bilateral paget disease of the nipple associated with lobular carcinoma in situ.

We report synchronous bilateral Paget disease derived from lobular carcinoma in situ in a 53-year-old woman who underwent bilateral mastectomy. The epidermis of both nipples contained small cells with a moderate amount of pale-staining cytoplasm. The nuclei had fine chromatin and identifiable nucleoli. The cells were strongly immunoreactive with cytokeratin 7 and displayed nuclear estrogen receptor reactivity. The underlying mammary gland showed involvement by lobular carcinoma in situ with pagetoid spread into lactiferous ducts, which was confirmed by lack of immunoreactivity for E-cadherin.

Breast Neoplasms↗
PubMed1999

[Dermatologic diseases of the nipple and areola].

Several diseases of the nipple and areola have a specific dermatological presentation. They may be classified into five main categories including dysembryoplasias, mastalgia, inflammatory dermatoses, hyperkeratoses and neoplasms.

Breast Diseases↗