Black Cohosh Does Not Exert an Estrogenic Effect on the Breast

Women's Health Initiative findings indicate that hormone replacement therapy may increase breast cancer and cardiovascular disease risk. Black cohosh extract (BCE) is a popular alternative that reduced menopausal symptoms in several clinical trials. Preclinical studies have addressed the estrogenic properties of BCE, with conflicting results. The estrogenic influence of BCE on the breast has not been investigated. Black cohosh is standardized to triterpenes, but the activity and mechanism of action of these compounds are unknown. The study goals were to determine 1) triterpene content of 2 commercially available BCE preparations and 2) the effect of BCE on circulating and breast-specific estrogenic markers. Two black cohosh preparations were analyzed for triterpene content. Postmenopausal women took BCE for 12 wk followed by a 12-wk washout. One BCE preparation contained trace amounts and another contained 2.5% triterpenes. Women taking BCE with 2.5% triterpenes experienced relief of menopausal symptoms, with reversion toward baseline after washout. BCE had no effect on estrogenic markers in serum and no effect on pS2 or cellular morphology in nipple aspirate fluid. Triterpene content in commercially available black cohosh preparations varies. BCE standardized to 2.5% triterpenes relieved menopausal symptoms without systemic or breast-specific estrogenic effects.     

Needle aspiration cytology of the irradiated breast.

During a 3-year period (1987-1989), 60 fine-needle aspiration biopsies (FNAs) were obtained from new breast lesions in patients previously treated by radiation and surgery for breast carcinoma. The lesions occurred at or near the site of previous excision, 3-117 months after initiation of radiotherapy. FNAs were classified as follows: acellular (11); negative (29); atypical (13); suspicious (4); and positive (3). For statistical analysis, acellular, negative, and atypical diagnoses were considered negative findings, and suspicious and positive diagnoses were considered positive findings. On the basis of subsequent biopsy and/or patient follow-up, FNA yielded a sensitivity of 86%, a specificity of 98%, a positive predictive value of 86%, a negative predictive value of 98%, and an efficiency of 97%. Excluding cystic lesions, the most reliable criterion for distinguishing malignant from benign lesions was the abundance of epithelial cells, both singly and in large clusters. Cellular characteristics were less helpful, since nuclear atypia was seen in both benign and malignant lesions. It is concluded that (1) FNA is a reliable technique in the evaluation of the irradiated breast; (2) when performed by an experienced operator, an acellular aspirate may be interpreted as evidence against recurrent carcinoma; and (3) epithelial atypia must be interpreted with caution to avoid a false-positive diagnosis.     

Cytologic approach to tumors of the tracheobronchial tree

Cytologic testing is an integral part of the workup of patients suspected of having lung cancer. These tests are less invasive than other tissue procurement methods, with minimal risk of complications. In experienced hands, the tests are highly accurate and reliable. To achieve good results and avoid diagnostic errors, clinicians must be educated in proper collection and fixation methods and the pathologist should be cognizant of clinical and radiologic data. Close communication between the clinician and pathologist should be encouraged.     

Utilization of ancillary studies in the cytologic diagnosis of biliary and pancreatic lesions: The papanicolaou society of cytopathology guidelines for pancreatobiliary cytology

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound‐guided fine‐needle aspiration, terminology and nomenclature of pancreatobiliary disease, ancillary testing, and post‐biopsy management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings, and synthesis of selected online comments of the draft document. This document presents the results of these discussions regarding the use of ancillary testing in the cytologic diagnosis of biliary and pancreatic lesions. Currently, fluorescence in situ hybridization (FISH) appears to be the most clinically relevant ancillary technique for cytology of bile duct strictures. The addition of FISH analysis to routine cytologic evaluation appears to yield the highest sensitivity without loss in specificity. Loss of immunohistochemical staining for the protein product of the SMAD4 gene and positive staining for mesothelin support a diagnosis of ductal adenocarcinoma. Immunohistochemical markers for endocrine and exocrine differentiation are sufficient for a diagnosis of endocrine and acinar tumors. Nuclear staining for beta‐catenin supports a diagnosis of solid‐pseudopapilary neoplasm. Cyst fluid analysis for amylase and carcinoembryonic antigen aids in the preoperative classification of pancreatic cysts. Many gene mutations (KRAS, GNAS, VHL, RNF43, and CTNNB1) may be of aid in the diagnosis of cystic neoplasms. Other ancillary techniques do not appear to improve diagnostic sensitivity sufficiently to justify their increased costs. Diagn. Cytopathol. 2014;42:351–362. © 2014 Wiley Periodicals, Inc.     

Microsatellite changes in nipple aspirate fluid and breast tissue from women with breast carcinoma or its precursors.

PURPOSE: Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been identified in a variety of human cancers. The purpose of this prospective study was to determine whether (a) DNA can be isolated from nipple aspirate fluid (NAF) and PCR amplified to large fragments, (b) LOH and MSI are detectable in NAF, and (c) LOH and MSI in tissue and NAF increase with disease progression from precursor lesions to cancer. Experimental Design: Forty-six matched samples from breast lesions, normal breast, and NAF were microdissected, and DNA was extracted. Eleven microsatellite markers from seven chromosomes that have a high frequency of LOH/MSI in breast cancer were designed and respectively amplified. RESULTS: LOH and/or MSI were identified in 22 of 46 (48%) breast lesions, including LOH in 8 of 36 (22%) proliferative/papilloma (P/Pap) and 7 of 10 (70%) cancer specimens, whereas MSI was found in 14 of 36 (39%) P/Pap and 6 of 10 (60%) cancer specimens. LOH/MSI loci in which alterations were detected in the 22 tissue specimens were PCR amplified using matched NAF DNA. LOH/MSI was detected in NAF from both P/Pap (5 of 15; 33%) and breast cancer (3 of 7; 43%) samples. CONCLUSIONS: Our findings suggest that (a) DNA from NAF, a physiological fluid collected noninvasively, can be PCR amplified and used to screen for LOH and MSI alterations that are known to be linked to breast cancer, suggesting that this methodology might prove useful for breast cancer screening, and (b) similar to findings in breast tissue, LOH and MSI alterations increase in frequency with disease progression in NAF, which suggests that NAF is a surrogate for breast tissue which has important prognostic implications.     

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.     

Fiberoptic ductoscopy findings in women with and without spontaneous nipple discharge

BACKGROUND: Fiberoptic ductoscopy (FD), which allows direct visualization of the breast ductal lumen, is performed in women with and without spontaneous nipple discharge (SND). Previous reports suggested that cytologic evaluation of SND may be falsely interpreted as containing malignancy. The purpose of the current study, which was performed prospectively, was to determine whether ductoscopic findings were different in women with versus without SND, and to assess the implications of the differences in SND versus non-SND samples regarding the role of FD in assessing whether a woman has breast carcinoma. METHODS: Data were collected on the distance traveled by the ductoscope, visual observations, pathology, cytology, epithelial and foam cell quantity, and image analysis for ploidy, hypertetraploidy, and S-phase fraction. RESULTS: Of 100 FD specimens, 60 were from breasts without SND and 40 were from breasts with SND. Intraductal visual observations (P < or = 0.0002), pathologic findings in the resected specimen (P < or = 0.001), and quantity of epithelial cells (P=0.03) were influenced by the presence or absence of SND. Although one specimen from a benign breast was interpreted as cytologically malignant, every breast with both malignant cytology and aneuploidy contained cancer cells. A model incorporating cytology and SND was 92% sensitive and 60% specific in predicting which women had breast carcinoma. CONCLUSIONS: There were pronounced differences in FD samples from women with and without SND. FD biologic parameters can be chosen to optimize breast carcinoma predictive sensitivity and specificity. SND cytology can present a diagnostic problem, suggesting the need for histologic confirmation before the initiation of therapy.