OBJECTIVE: To analyze the cytologic features of nipple discharge and fine needle aspiration (FNA) cytologic smears from breast lesions reported as showing papillary features and to correlate them with histopathologic features.
STUDY DESIGN: The study group consisted of FNA smears and/or nipple discharge smears from 65 breast lesions diagnosed on cytology as duct papilloma, papillary lesion, fibrocystic condition, fibroadenoma, papillary neoplasm or papillary carcinoma. Cytomorphologic features assessed included cellularity, cell pattern (clusters, papillary, 3-dimensionality, etc.) and cell characteristics (monomorphism, pleomorphism, apocrine change, plasmacytoid features). Histological material was available for review and cytohistologic correlation in all cases.
RESULTS: Forty-six specimens were FNA smears, and 16 were nipple discharge smears; in 3 cases FNA and nipple discharge cytologic smears were available for review. Cytologic study could predict the presence of a papillary pattern in all neoplasms with pure or focal papillary differentiation. There was an overlap in cytomorphologic features between papillary and nonpapillary benign lesions as well as between benign and malignant papillary neoplasms. Frank blood in the aspirate, cell dissociation and atypia, however, were more frequent in the last.
CONCLUSION: Overlap of cytologic features in nonneoplastic and neoplastic benign papillary lesions and between benign and malignant papillary neoplasms necessitates histologic evaluation in all cases diagnosed as papillary on cytology. Since 49.2% of lesions showing papillary features on cytology prove to be malignant, all cases reported as papillary on cytology should be excised urgently for histologic assessment.
Introduction: Mammography is commonly regarded as the single most important tool for screening and for early detection of breast cancer. However it is not generally recommended for women under 40 years of age and in those taking hormone replacement therapy as the increased density of the breast parenchyma may make mammography more difficult to read and interpret. The limitations of mammography have spurred attempts to find new techniques that can be used either separately or in conjunction with mammography. Purpose: The aim of this study was to quantify the clinical value of using electrical impedance scanning (EIS) or Trans Scan as an adjunct to mammography in order to identify cancerous tissue based upon its inherent altered local dielectric properties. Methods and Materials: The patients were examined using Trans Scan (Trans Scan Medical, Ltd., distributed by Siemens AG. The study population was derived from patients with suspicious breast lesions categorized as BIRADS 3 or 4 detected during mammography or ultrasound. Results: Fifty-three women with 53 mammographically and/or sonographically suspicious findings were examined using EIS. With respect to the histopathological findings (15 malignant and 38 benign lesions) 13 of 15 (86.6% sensitivity) malignant lesions were correctly identified using EIS whereas, 33 of 38 (81.5% specificity) benign lesions were correctly identified. Negative and positive predictive values of 93.9% and 65% were observed respectively. Two benign lesions were correctly identified in a dense breast. The smallest lesion detected in this study measured 20 x 14 mm, which was an infiltrating ductal carcinoma. Conclusion: Electrical impedance scanning as an adjunct to mammography or ultrasound in classifying suspicious lesions is promising because it increases the sensitivity for cancer detection and may reduce biopsy of equivocal lesions. The additional use of EIS with negative predictive value of 93.9% may be useful to exclude some benign lesions from further diagnostic or invasive procedures. Artifacts, such as signals from superficial skin lesions, poor contact and bubbles are currently a limitation
Invasive Lobular Carcinoma of the breast is less common than Invasive Ductal Carcinoma and the presentation can be different from other types of breast carcinomas. It can present as diffuse swelling or thickening of breast rather than a mass. Sometimes, it can present as metastatic deposits from a very small primary breast lesion. These make the diagnosis of this type of breast carcinoma difficult and challenging for the radiologist and surgeon. We describe a case of Invasive Lobular Carcinoma of the breast, which presented with a left sterno-chondral metastasis and discuss the imaging findings and treatment of this condition.
Data on dietary exposure to vitamin E by plasma or adipose tissue concentrations of alpha-tocopherol (alpha-T) in observational studies have failed to provide consistent support for the idea that alpha-T provides women with any protection from breast cancer. In contrast, studies indicate that alpha, gamma, and delta-tocotrienols but not alpha-T have potent anti-proliferative effects in human breast cancer cells. Our aim was to investigate whether there was a difference in tocopherol and tocotrienol concentrations in malignant and benign adipose tissue, in a Malaysian population consuming predominantly a palm oil diet. The study was undertaken using fatty acid levels in breast adipose tissue as a biomarker of qualitative dietary intake of fatty acids. The major fatty acids in breast adipose tissue of patients (benign and malignant) were oleic acid (45-46%), palmitic (28-29%) and linoleic (11-12%). No differences were evident in the fatty acid composition of the two groups. There was a significant difference (p=0.006) in the total tocotrienol levels between malignant (13.7 +/- 6.0 microg/g) and benign (20+/-6.0 microg/g) adipose tissue samples. However, no significant differences were seen in the total tocopherol levels (p=0.42) in the two groups. The study reveals that dietary intake influences adipose tissue fatty acid levels and that adipose tissue is a dynamic reservoir of fat soluble nutrients. The higher adipose tissue concentrations of tocotrienols in benign patients provide support for the idea that tocotrienols may provide protection against breast cancer.
Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.
Matched MeSH terms: Breast Neoplasms/drug therapy*; Breast Neoplasms/enzymology; Breast Neoplasms/ethnology; Breast Neoplasms/genetics; Breast Neoplasms/metabolism
Although many factors have been suggested as causes for breast cancer, the increased incidence of the disease seen in women working in night shifts led to the hypothesis that the suppression of melatonin by light or melatonin deficiency plays a major role in cancer development. Studies on the 7,12-dimethylbenz[a]anthracene and N-methyl-N-nitrosourea experimental models of human breast cancer indicate that melatonin is effective in reducing cancer development. In vitro studies in MCF-7 human breast cancer cell line have shown that melatonin exerts its anticarcinogenic actions through a variety of mechanisms, and that it is most effective in estrogen receptor (ER) alpha-positive breast cancer cells. Melatonin suppresses ER gene, modulates several estrogen dependent regulatory proteins and pro-oncogenes, inhibits cell proliferation, and impairs the metastatic capacity of MCF-7 human breast cancer cells. The anticarcinogenic action on MCF-7 cells has been demonstrated at the physiological concentrations of melatonin attained at night, suggesting thereby that melatonin acts like an endogenous antiestrogen. Melatonin also decreases the formation of estrogens from androgens via aromatase inhibition. Circulating melatonin levels are abnormally low in ER-positive breast cancer patients thereby supporting the melatonin hypothesis for breast cancer in shift working women. It has been postulated that enhanced endogenous melatonin secretion is responsible for the beneficial effects of meditation as a form of psychosocial intervention that helps breast cancer patients.
Matched MeSH terms: Breast Neoplasms/etiology*; Breast Neoplasms/physiopathology*
The aim of this study is to assess tissue and serum prostate-specific antigen (PSA) in breast lesions; to compare tissue PSA with serum PSA; to compare tissue PSA in benign and malignant lesions and to compare PSA with known prognostic factors in breast carcinoma. Tissue PSA immunoreactivity in twenty women with breast carcinoma was compared with PSA in twenty-three women with benign breast lesions. Tissue PSA was also compared with known prognostic indicators such as tumour size, axillary nodal status, histological type, histological grade, oestrogen receptor status, progesterone receptor status and c-erbB-2 oncoprotein over-expression. Serum free PSAlevels from these women were measured pre- and post-operatively and an attempt was made to correlate serum PSA with tissue PSA expression. 40% and 43% of malignant and benign breast lesions respectively showed tissue PSA immunoreactivity. No significant difference was observed in the tissue PSA expression between these two groups as also between tissue PSA and known prognostic indicators. As serum PSA levels were below the detection limit (< 0.004 ng/ml) in all except two benign cases, no statistical evaluation was done for the latter. Tissue PSA expression did not correlate with other prognostic markers and detectable serum PSA levels were present in too few cases for statistical analysis. Although no definitive conclusion is possible in this preliminary study regarding the role of PSA in breast disease, it stimulates interest in further research in this direction.
Matched MeSH terms: Breast Neoplasms/metabolism*; Breast Neoplasms/pathology
Neuroendocrine carcinomas of the breast are uncommon tumors known to occur in the elderly. While focal neuroendocrine differentiation may be noted in many ductal and lobular carcinomas, the term neuroendocrine carcinoma is to be applied when more than 50% of the tumor shows such differentiation. This case report details the cytological features of a neuroendocrine carcinoma that was encountered in our hospital. The fine needle aspiration (FNA) smears showed discohesive polygonal cells with abundant cytoplasm, many of which contained eosinophilic granules located at one pole. Histology of the mastectomy and axillary lymph nodes specimen from this patient showed features of neuroendocrine carcinoma--solid type, with metastasis, confirmed with immunohistochemistry. The patient is disease free seven months after surgery. This case highlights the need to closely observe cytological details to identify this rare tumor that may otherwise appear to be invasive duct carcinoma--not otherwise specified on FNA. The implications of diagnosing neuroendocrine differentiation for prognosis and management are also discussed.
Matched MeSH terms: Breast Neoplasms/metabolism; Breast Neoplasms/pathology*; Breast Neoplasms/surgery*
A 35 kDa glycoprotein whose abundance was previously demonstrated to be enhanced in sera of patients with endometrial adenocarcinoma (n = 12), was isolated from pooled sera of three of the cancer patients using champedak galactose-binding lectin affinity chromatography in the present study. Subjecting it to 2-DE and MS/MS, the glycoprotein was identified as the O-glycosylated fragment of inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4). When compared to control sera (n = 17), expression of the 35 kDa ITIH4 cleavage fragment was demonstrated to be significantly enhanced in sera of patients with breast carcinoma (n = 10), epithelial ovarian carcinoma (n = 10), and germ cell ovarian carcinoma (n = 10) but not in patients with nasopharyngeal carcinoma (n = 13) and osteosarcoma (n = 7). The lectin-based electrophoretic bioanalytical method adopted in the present study may be used to assess the physiological relevance of ITIH4 fragmentation and its correlation with different malignancies, their stages and progression.
A 74-year-old woman was incidentally found to have a left breast mass. The mass could not be adequately compressed to be visualized on mammography. Ultrasonography showed a heavily-calcified rounded mass in the left axillary tail of the left breast. Chest radiograph confirmed that the mass was a migrated humeral head. Remotely-displaced fracture-dislocations of the humeral head are very rare and to our knowledge, displacement into the breast, clinically mimicking a breast mass, has not been previously described.
The p53 gene is a tumour suppressor gene that encodes a 393-amino-acid nuclear DNA-binding phosphoprotein. The significance of p53 detection is that p53 mutation is linked with chemo-resistance and transformation to more aggressive disease in a large number of tumour types and it was confirmed that mutant p53 is involved in neoplastic transformations. In addition, the expression of p53 has been closely correlated with clinicopathological findings. Since breast cancer has been reported as one of the most frequent malignancies in women in Malaysia, the expression of p53 was studied in 382 cases of invasive ductal carcinoma of the breast, obtained from three major hospitals in the North-East States of Malaysia. The study utilized an enzyme immunohistochemistry assay for the detection of p53. It was found that p53 was expressed in 29.6% of all the study cases. Furthermore, its expression was significantly correlated with the age and the clinical grading of the disease. No significant statistical correlations were depicted with lymph node status, tumour size, side of tumour, and expression of estrogen and progesterone receptors. Nevertheless, knowledge of the p53 status may be valuable in making clinical decisions regarding diagnosis, prognosis and therapy.
Breast cancer is the most common cancer in most part of the world and it is the most common cancer among Malaysian women. In order to estimate the overall survival and prognosis, it was decided that a National Cancer Patient Registry-Breast cancer be set up. It would be a tracking system form for breast cancer patients in Malaysia to help treatment outcomes. There would be useful for evaluating clinical management.
Matched MeSH terms: Breast Neoplasms/drug therapy; Breast Neoplasms/mortality; Breast Neoplasms/epidemiology*; Breast Neoplasms/surgery
Primary sarcomas of the breast are extremely rare comprising less than 1.0% of all malignant tumors of the breast. It is even rarer to be reported in a 25-year-old female. This can cause a diagnostic dilemma not only for the clinician but also for the cytopathologist. A 25-year-old woman presented with a well defined firm, mobile lump in her right breast. With fine needle aspiration cytology (FNAC) and ultrasonography a diagnosis of fibroadenoma was made. The patient underwent lumpectomy. Histopathologically it was diagnosed as myxoid liposarcoma. This case is reported to highlight the fact that, even though rare in young females but the possibility of a breast lump being a myxoid liposarcoma does exist. This report discusses a primary myxoid liposarcoma of female breast, considers cytologic differential diagnoses with review of the relevant literature.
Matched MeSH terms: Breast Neoplasms/diagnosis*; Breast Neoplasms/pathology*
Chromatin morphologies in human breast cancer cells treated with an anti-cancer agent are analyzed at their early stage of programmed cell death or apoptosis. The gray-level images of nuclear chromatin are modelled as random fields. We used two-dimensional isotropic generalized Cauchy field to characterize local self-similarity and global long-range dependence behaviors in the image spatial data. Generalized Cauchy field allows the description of fractal behavior inferred from fractal dimension and the long-range dependence inferred from correlation exponent to be carried out independently. We demonstrated the usefulness of locally self-similar random fields with long-range dependence for modelling chromatin condensation.
Matched MeSH terms: Breast Neoplasms/pathology*; Breast Neoplasms/ultrastructure*
We report on a Malaysian kindred with Li-Fraumeni syndrome. The proband was an 8-year-old girl who presented with embryonal rhabdomyosarcoma of the trunk at the age of 8 months and developed a brain recurrence at the age of 7 years, which was 5 years after remission. A younger sister later developed adrenocortical carcinoma at the age of 6 months. Their mother and maternal grandmother were diagnosed with breast cancer at the ages of 26 and 38 years, respectively. TP53 mutation detection in this family revealed a duplication of a GGCGTG motif starting at nucleotide 17579 in exon 10, resulting in an in-frame insertion of two amino acids between residues 334 and 336 in the tetramerization domain of the p53 protein. This mutation was found in the proband and her affected sister as well as her mother. In addition, the mutation was detected in two other siblings (a brother aged 3 years and a sister aged 18 months) who have not yet developed any malignancy. Sequencing of TP53 in the father and two other asymptomatic siblings revealed wild-type TP53. To our knowledge, this is a first report of a Li-Fraumeni syndrome family in Southeast Asia.
This is a study aimed to examine the distribution pattern of a specific minichromosome maintenance protein 2 (MCM2) in benign and malignant breast tissue. We also aim to correlate the frequency of expression of MCM2 with the degree of tumor differentiation. We used immunohistochemistry to examine the distribution and expression pattern of MCM2 on formalin-fixed paraffin-embedded tissue sections of benign (n = 30) and malignant breast tissue (n = 70) (IDC 56, DCIS 4, ILC 2, nonductal 4, mixed type 4). We quantified MCM2 expression by calculating a labeling index, which represents the percentage of epithelial nuclei that stained positively. Immunoreactivity was heterogenous in all the 70 malignant cases examined. Epithelial cells in cycle are most frequent at the tumor periphery. Labeling index of MCM2 was greatest in grade 3 (poorly differentiated) and lowest in grade 1 tumors (well differentiated). Minichromosome maintenance protein 2 expression in breast cancer showed a positive association with histologic grade (P < .05). In all the benign breast tissue examined, no proliferating compartments could be characterized. Minichromosome maintenance protein 2 is a useful proliferative marker of breast carcinoma. The frequency of expression of MCM2 showed an inverse correlation with the degree of tumor differentiation.
Matched MeSH terms: Breast Neoplasms/metabolism*; Breast Neoplasms/pathology
A key determinant of breast cancer outcome in any population is the degree to which cancers are detected at early stages of disease. Populations in which cancers are detected at earlier stages have lower breast cancer mortality rates. The Breast Health Global Initiative (BHGI) held its third Global Summit in Budapest, Hungary in October 2007, bringing together internationally recognized experts to address the implementation of breast healthcare guidelines for early detection, diagnosis, and treatment in low- and middle-income countries (LMCs). A multidisciplinary panel of experts specifically addressed the implementation of BHGI guidelines for the early detection of disease as they related to resource allocation for public education and awareness, cancer detection methods, and evaluation goals. Public education and awareness are the key first steps, because early detection programs cannot be successful if the public is unaware of the value of early detection. The effectiveness and efficiency of screening modalities, including screening mammography, clinical breast examination (CBE), and breast self-examination, were reviewed in the context of resource availability and population-based need by the panel. Social and cultural barriers should be considered when early detection programs are being established, and the evaluation of early detection programs should include the use of well developed, methodologically sound process metrics to determine the effectiveness of program implementation. The approach and scope of any screening program will determine the success of any early detection program as measured by cancer stage at diagnosis and will drive the breadth of resource allocation needed for program implementation.
Matched MeSH terms: Breast Neoplasms/diagnosis*; Breast Neoplasms/economics; Breast Neoplasms/therapy*
Breast cancer is the leading cause of cancer deaths in Malaysian women, and the use of breast self-examination (BSE), clinical breast examination (CBE) and mammography remain low in Malaysia. Therefore, there is a need to develop a valid and reliable tool to measure the beliefs that influence breast cancer screening practices. The Champion's Health Belief Model Scale (CHBMS) is a valid and reliable tool to measure beliefs about breast cancer and screening methods in the Western culture. The purpose of this study was to translate the use of CHBMS into the Malaysian context and validate the scale among Malaysian women.
Matched MeSH terms: Breast Neoplasms/diagnosis*; Breast Neoplasms/epidemiology*
BACKGROUND AND PURPOSE: Andrographolide, the major phytoconstituent of Andrographis paniculata, was previously shown by us to have activity against breast cancer. This led to synthesis of new andrographolide analogues to find compounds with better activity than the parent compound. Selected benzylidene derivatives were investigated for their mechanisms of action by studying their effects on the cell cycle progression and cell death.
EXPERIMENTAL APPROACH: Microculture tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays were utilized in assessing the in vitro growth inhibition and cytotoxicity of compounds. Flow cytometry was used to analyse the cell cycle distribution of control and treated cells. CDK1 and CDK4 levels were determined by western blotting. Apoptotic cell death was assessed by fluorescence microscopy and flow cytometry.
KEY RESULTS: Compounds, in nanomolar to micromolar concentrations, exhibited growth inhibition and cytotoxicity in MCF-7 (breast) and HCT-116 (colon) cancer cells. In the NCI screen, 3,19-(2-bromobenzylidene) andrographolide (SRJ09) and 3,19-(3-chloro-4-fluorobenzylidene) andrographolide (SRJ23) showed greater cytotoxic potency and selectivity than andrographolide. SRJ09 and SRJ23 induced G(1) arrest and apoptosis in MCF-7 and HCT-116 cells, respectively. SRJ09 downregulated CDK4 but not CDK1 level in MCF-7 cells. Apoptosis induced by SRJ09 and SRJ23 in HCT-116 cells was confirmed by annexin V-FITC/PI flow cytometry analysis.
CONCLUSION AND IMPLICATIONS: The new benzylidene derivatives of andrographolide are potential anticancer agents. SRJ09 emerged as the lead compound in this study, exhibiting anticancer activity by downregulating CDK4 to promote a G(1) phase cell cycle arrest, coupled with induction of apoptosis.
Matched MeSH terms: Breast Neoplasms/drug therapy; Breast Neoplasms/enzymology; Breast Neoplasms/pathology