Breast Tumors (breast + tumor)

Distribution by Scientific Domains
Medical Sciences75%
Life Sciences17%
Chemistry4%
Distribution within Medical Sciences
Oncology & Radiotherapy60%
Pathology9%

Kinds of Breast Tumors

  • primary breast tumor
    		•

    Selected Abstracts

    Molecular Breast Imaging: Advantages and Limitations of a Scintimammographic Technique in Patients with Small Breast Tumors

    THE BREAST JOURNAL, Issue 1 2007
    Michael K. O'Connor PhD
    Abstract:, Preliminary studies from our laboratory showed that molecular breast imaging (MBI) can reliably detect tumors <2 cm in diameter. This study extends our work to a larger patient population and examines the technical factors that influence the ability of MBI to detect small breast tumors. Following injection of 740 MBq Tc-99m sestamibi, MBI was performed on 100 patients scheduled for biopsy of a lesion suspicious for malignancy that measured <2 cm on mammography or sonography. Using a small field of view gamma camera, patients were imaged in the standard mammographic views using light pain-free compression. Subjective discomfort, breast thickness, the amount of breast tissue in the detector field of view, and breast counts per unit area were measured and recorded. Follow-up was obtained in 99 patients; 53 patients had 67 malignant tumors confirmed at surgery. Of these, 57 of 67 were detected by MBI (sensitivity 85%). Sensitivity was 29%, 86%, and 97% for tumors <5, 6,10, and ,11 mm in diameter, respectively. In seven patients, MBI identified eight additional mammographically occult tumors. Of 47 patients with no evidence of cancer at biopsy or surgery, there were 36 true negative and 11 false positive scans on MBI. MBI has potential for the regular detection of malignant breast tumors less than 2 cm in diameter. Work in progress to optimize the imaging parameters and technique may further improve sensitivity and specificity. [source]

    Trends in Benign Breast Tumors in Japanese Women, 1973,1995: Experience of Hiroshima Tumor Tissue Registry

    CANCER SCIENCE, Issue 6 2002
    Koji Arihiro
    Although some benign breast lesions such as multiple intraductal papilloma have been pointed out as a risk factor for breast cancer, there is little documentation about trends in the incidence of benign tumors of the breast in Japanese women. The author conducted an epidemiological study using data abstracted from the Hiroshima Tumor Tissue Registry file, which includes cases of malignant and benign neoplasms in Hiroshima prefecture between 1973 and 1995. A total of 17 064 cases of female breast tumor were registered in the file between 1973 and 1995. The registration rate for fibroadenoma of the female breast was 19.5 among females and peaked during the 5-year period 1983,1987, while the fibroadenoma registration rate in Hiroshima gradually decreased between 1988 and 1995. The registration rate for intraductal papilloma has risen substantially in Hiroshima, with about a 5-fold increase among females between 1973 and 1995. The mean proportion of fibroadenoma cases accompanied by malignant tumors of the breast was 1.85%, and there was no significant change in the mean proportion between 1973 and 1995 (P=0.17). On the other hand, the mean proportion of intraductal papilloma cases accompanied by malignant tumors of the breast gradually rose with about a 14-fold increase among females between 1973 and 1995. The significance of intraductal papilloma as a risk factor for breast cancer may have increased. [source]

    Evidence for shutter-speed variation in CR bolus-tracking studies of human pathology

    NMR IN BIOMEDICINE, Issue 3 2005
    Thomas E. Yankeelov
    Abstract The standard pharmacokinetic model for the analysis of MRI contrast reagent (CR) bolus-tracking (B-T) data assumes that the mean intracellular water molecule lifetime (,i) is effectively zero. This assertion is inconsistent with a considerable body of physiological measurements. Furthermore, theory and simulation show the B-T time-course shape to be very sensitive to the ,i magnitude in the physiological range (hundreds of milliseconds to several seconds). Consequently, this standard model aspect can cause significant underestimations (factors of 2 or 3) of the two parameters usually determined: Ktrans, the vascular wall CR transfer rate constant, and ve, the CR distribution volume (the extracellular, extravascular space fraction). Analyses of animal model data confirmed two predicted behaviors indicative of this standard model inadequacy: (1) a specific temporal pattern for the mismatch between the best-fitted curve and data; and (2) an inverse dependence of the curve's Ktrans and ve magnitudes on the CR dose. These parameters should be CR dose-independent. The most parsimonious analysis allowing for realistic ,i values is the ,shutter-speed' model. Its application to the experimental animal data essentially eliminated the two standard model signature inadequacies. This paper reports the first survey for the extent of this ,shutter-speed effect' in human data. Retrospective analyses are made of clinical data chosen from a range of pathology (the active multiple sclerosis lesion, the invasive ductal carcinoma breast tumor, and osteosarcoma in the leg) that provides a wide variation, particularly of Ktrans. The signature temporal mismatch of the standard model is observed in all cases, and is essentially eliminated by use of the shutter-speed model. Pixel-by-pixel maps show that parameter values from the shutter-speed analysis are increased by more than a factor of 3 for some lesion regions. This endows the lesions with very high contrast, and reveals heterogeneities that are often not seen in the standard model maps. Normal muscle regions in the leg allow validation of the shutter-speed model Ktrans, ve, and ,i magnitudes, by comparison with results of previous careful rat leg studies not possible for human subjects. Copyright © 2004 John Wiley & Sons, Ltd. [source]

    Low-grade periductal stromal sarcoma of the breast with myxoid features: Immunohistochemistry

    PATHOLOGY INTERNATIONAL, Issue 8 2009
    Davor Tomas
    A 52-year-old woman was admitted with a painful right breast tumor measuring more than 20 cm in largest diameter, which ulcerated the overlying skin. The lesion had appeared 4 years previously but the patient hesitated to seek medical care due to ,fear of cancer'. Microscopically, the tumor was composed of spindle cells that formed cuffs around multiple open tubules and ducts set in an abundant, myxoid stroma. The spindle cells had significant atypia with nuclear pleomorphism, occasional cytoplasmic vacuolation and moderate mitotic activity. The ducts and lobules surrounded by the proliferating tumor cells had minimal distortion, with a pericanalicular growth pattern devoid of the phyllodes pattern. The tumor had a multinodular growth pattern with coalesced and individual tumor nodules, the latter being found mostly at the periphery of the lesion. On immunohistochemistry the tumor cells were positive for smooth muscle actin, CD34, and vimentin, and focally positive for CD10. A diagnosis of low-grade periductal stromal sarcoma (PDSS) with myxoid features was established. PDSS is a distinct low-grade breast sarcoma, the appropriate diagnosis of which requires extensive tumor sampling and additional broad immunohistochemistry. PDSS should not be confused with other spindle cell breast tumors because they require different treatment. [source]

    Signet-ring cell carcinoma of the breast

    PATHOLOGY INTERNATIONAL, Issue 1 2000
    Shian-Min Liu
    Primary signet-ring cell carcinoma of the breast is a very rare tumor and is not recognized as an independent entity of the World Health Organization classification of breast tumor. Primary signet-ring cell carcinoma of the breast is usually considered as a variant of mucinous carcinoma or lobular carcinoma and usually originates from the lobular epithelium. A case of primary signet-ring cell carcinoma of the breast in a 68-year-old woman is presented. Histologically, the majority of neoplastic cells had an intracytoplasmic mucin collection. The histological presence of ductal carcinoma in situ, absence of lobular lesion and immunoreactivity for estrogen and progesterone receptors implicated the tumor cells arising from ductal epithelium. The papillary or organoid growth pattern is characteristic in this case. The patient underwent a modified radical mastectomy and was subsequently followed up for 6 months. [source]

    Effect of Photothermal Therapy on Breast Tumor Vascular Contents: Noninvasive Monitoring by Near-infrared Spectroscopy,

    PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2005
    Yueqing Gu
    ABSTRACT The goal of this study was to investigate the effect of photothermal laser irradiation on rat breast tumor (DMBA-4) vascular contents. An 805-nm diode laser was used in our experiment with a power density ranging from 0.32 to 1.27 W/cm2. The dynamic changes of oxygenated hemoglobin and total hemoglobin concentrations, ,[HbO2] and ,[Hb]total, in rat tumors during photothermal irradiation were noninvasively monitored by a near-infrared spectroscopy system. A multichannel thermal detection system was also used simultaneously to record temperatures at different locations within the tumors. Our experimental results showed that: (1) photoirradiation did have the ability to induce hyperthermic effects inside the rat breast tumors in a single exponential trend; (2) the significant changes (P < 0.005) of ,[HbO2] and ,[Hb]total in response to a low dosage of laser irradiation (0.32 W/cm2) have a single exponential increasing trend, similar to that seen in the tumor interior temperature; and (3) the increase in magnitude of ,[Hb]total is nearly two times greater than that of ,[Hb]total, suggesting that photoirradiation may enhance tumor vascular oxygenation. The last observation may be important to reveal the hidden mechanism of photoirradiation on tumors, leading to improvement of tumor treatment efficiency. [source]

    Breast Intracystic Papillary Carcinoma: An Update

    THE BREAST JOURNAL, Issue 6 2009
    Julien Calderaro
    Abstract:, Intracystic papillary carcinoma (IPC), a breast tumor mainly occuring in the elderly, has long been considered as a variant of ductal carcinoma in situ (DCIS). This is now debated since metastatic cases have been reported. In this study, surgical pieces of 20 IPCs were reassessed, and markers of myopepithelial layer (p63, CD10 and Smooth Muscle Actin) as well as estrogen receptors (ER) and progesterone receptors (PgR) and C-erb-B2 oncoprotein expression were systematically performed and quantified. In 10 cases, an associated unequivocal invasive component was found. In all 20 cases, no myoepithelial layer was found. Eighteen tumors were ER positive, 14 were PgR positive. Moreover, none of the tumors over-expressed C-erb-B2 oncoprotein. Therefore this study showed that in all cases of IPC there were microscopic features of invasive carcinoma despite good clinical prognostic indicators, and that precise characterization of tumors requires extensive paraffin embedding of surgical pieces. [source]

    Pro-Opiomelanocortin Expression in a Metastatic Breast Carcinoma with Ectopic ACTH Secretion

    THE BREAST JOURNAL, Issue 4 2004
    Marie-Françoise Pelte MD
    Abstract: Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion is rarely observed in breast carcinoma and only four cases have been previously published. We report here the case of a 50-year-old woman who presented with a history of diffuse bone pain associated with multiple hepatic, pulmonary, and bone metastases. A core needle biopsy specimen revealed an invasive ductal carcinoma in the right breast. The patient subsequently developed an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia and heart failure, despite treatment. At autopsy, immunohistochemical staining showed chromogranin A and ACTH positivity in the breast tumor and a lung metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT-PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH secretion where the presence of ACTH by immunohistochemistry and the expression of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with metastases. The clinical history and the pathologic findings are presented with the methods and results of the molecular analysis. This case illustrates an example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE) differentiation. This NE phenotype is directly related to the synthesis of ACTH by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may be produced not only by small cell carcinoma or endocrine tumors but also by breast cancer. No relationship has been established between NE features and prognostic factors or patient outcome for this peculiar type of breast carcinoma. The demonstration of mRNA POMC in breast carcinoma with NE features suggests a depression and/or an activation of the POMC gene linked to the NE differentiation., [source]

    Local Recurrence of Breast Cancer in the Stereotactic Core Needle Biopsy Site: Case Reports and Review of the Literature

    THE BREAST JOURNAL, Issue 2 2001
    Celia Chao MD
    Abstract: Early mammographic detection of nonpalpable breast lesions has led to the increasing use of stereotactic core biopsies for tissue diagnosis. Tumor seeding the needle tract is a theorectical concern; the incidence and clinical significance of this potential complication are unknown. We report three cases of subcutaneous breast cancer recurrence at the stereotactic biopsy site after definitive treatment of the primary breast tumor. Two cases were clinically evident and relevant; the third was detected in the preclinical, microscopic state. All three patients underwent multiple passes during stereotactic large-core biopsies (14 gauge needle) followed by modified radical mastectomy. Two patients developed a subcutaneous recurrence at the site of the previous biopsy 12 and 17 months later; one had excision of the skin and dermis at the time of mastectomy revealing tumor cells locally. In summary, clinically relevant recurrence from tumor cells seeding the needle tract is reported in two patients after definitive surgical therapy (without adjuvant radiation therapy). Often, the biopsy site is outside the boundaries of surgical resection. Since the core needle biopsy exit site represents a potential area of malignant seeding and subsequent tumor recurrence, we recommend excising the stereotactic core biopsy tract at the time of definitive surgical resection of the primary tumor. [source]

    Axillary disease recurrence after sentinel lymph node dissection for breast carcinoma

    CANCER, Issue 9 2005
    Karen K. Swenson M.S., R.N.
    Abstract BACKGROUND Surgical recommendation for early-stage breast carcinoma includes removal of the primary breast tumor and evaluation of the axillary lymph nodes on the ipsilateral side. Sentinel lymph node dissection (SLND) is increasingly being used to evaluate axillary lymph nodes in clinically lymph node negative patients as an alternative to axillary lymph node dissection (ALND). Results from SLND are highly predictive of metastatic involvement in the axilla, and are associated with fewer side effects. However, the greatest concern with SLND alone is the potential for a higher rate of axillary lymph node recurrence. The purpose of the current study was to review data collected on 700 consecutive patients with early-stage breast carcinoma who underwent SLND without concomitant ALND. METHODS A retrospective study was conducted using the oncology registry at Park Nicollet Health Services (Minneapolis, MN). Consecutive breast carcinoma cases with SLND only for axillary surgery, from January 28, 1999 to December 31, 2003, were included in the study. During this period, 700 patients with breast carcinoma were identified who had SLND alone. Fifty-two patients were excluded from the analysis because they had ductal carcinoma in situ. RESULTS With a median follow-up of 33 months (range, 2-73 mos), axillary lymph node recurrence occurred in 4 of 647 (0.62%) patients overall. In these 4 patients, the axillary lymph node recurrences were isolated to the axillary lymph nodes and amenable to surgery. CONCLUSIONS Data from the current study showed that axillary lymph node recurrence after SLND occurred very infrequently in early-stage breast carcinoma, and these results were comparable to other studies. Cancer 2005. © 2005 American Cancer Society. [source]

    HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the metastatic process

    CANCER, Issue 8 2002
    Anne Vincent-Salomon M.D.
    Abstract BACKGROUND The objective of this study was to determine whether HER2 expression levels in breast carcinomas were modified by chemotherapy or during the metastatic process. METHODS HER2 expression was analyzed on sequential tissue specimens taken from the primary tumor before patients received preoperative chemotherapy (CT) and from post-CT residual breast tumor or at a metastatic site. The first group of patients included 59 women who presented with T2,T4,N1,N2 breast carcinoma and were treated by preoperative anthracycline-based CT and then underwent surgery. The second group included 44 patients with metastatic breast carcinoma localized to the lung (27 patients) or to the liver (17 patients). HER2 status was determined by immunohistochemistry using an anti-p185HER/neu monoclonal antibody and was classified as overexpressed or not overexpressed. RESULTS Among the patients who received preoperative CT, HER2 overexpression was observed in 15 of 59 patients (25%). A complete pathologic response was observed in 2 of these 15 patients. HER2 still was overexpressed in 11 of 13 remaining residual tumors and was no longer detectable in 2 tumors. In addition, the 29 tumors with no HER2 overexpression before CT remained negative after treatment. In patients with metastatic breast carcinoma, HER2 was overexpressed in 11 of 44 primary tumors (25%). In 9 of these 11 tumors, HER2 overexpression was maintained in the metastases (9 pulmonary metastases and 4 hepatic metastases). In two patients who had low levels of HER2 overexpression in their primary tumors, no staining was observed in the secondary tumor (one pulmonary tumor and one liver tumor). There were no tumors in which the overexpression of HER2 was found only in the metastasis. CONCLUSIONS The current study showed that, in most patients, HER2 overexpression was unchanged after CT and in metastatic sites. No HER2 negative primary tumors became HER2 positive after patients received CT or during the metastatic process. In a few patients, a diminution in the level of HER2 expression was observed after CT or in secondary tumors. This may have been due to a transitory state of altered tumor cells or to the selection of HER2 negative tumor cells clones. Cancer 2002;94:2169,73. © 2002 American Cancer Society. DOI 10.1002/cncr.10456 [source]

    Quantitative FISH analysis on interphase nuclei may improve diagnosis of DNA diploid breast cancers

    DIAGNOSTIC CYTOPATHOLOGY, Issue 4 2002
    Khuong Truong
    Abstract The detection of DNA aneuploid cells using flow cytometry is an indication for the presence of tumor cells, but when DNA diploid cells are found in 25,33% of the cases, the diagnostic and prognostic significance of DNA ploidy is more limited. We analyzed interphase nuclei after in situ hybridization and using image cytometry on 50 breast tumors with diploid DNA content to investigate whether early chromosome rearrangements were detectable and if their occurrence was clinically significant. Imbalances between the two arms of chromosome 1 were found in 55% of the cases and values ranged from 1.5,3.0. Comparison with histological data showed that Grade I tumors mainly have imbalances (67%) and that Grade III tumors were mainly without the imbalance (67%), whereas Grade II tumors were intermediate (50% imbalance). These data suggest that the diagnosis of DNA diploid cases may be improved by using interphase FISH. In addition, the data also indicates that early breast tumors may have different genetic origins, which is important in the comprehension of tumor malignancy in early stages, especially for preinvasive lesions. Diagn. Cytopathol. 2002;26:213,216. © 2002 Wiley-Liss, Inc. [source]

    Human exposure to heterocyclic amine food mutagens/carcinogens: Relevance to breast cancer ,

    ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2-3 2002
    James S. Felton
    Abstract Heterocyclic amines produced from overcooked foods are extremely mutagenic in numerous in vitro and in vivo test systems. One of these mutagens, 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP), induces breast tumors in rats and has been implicated in dietary epidemiology studies as raising the risk of breast cancer in humans. Efforts in our laboratory and others have centered on defining the exposure to PhIP and other dietary mutagens derived from cooked food. We accomplish this by analyzing the foods with a series of solid-phase extractions and HPLC. We have developed an LC/MS/MS method to analyze the four major human PhIP metabolites (sulfates and glucuronides) following a single meal containing 27 ,g of cooking-produced PhIP in 200 g of grilled meat. Although the intake of PhIP was similar for each of eight women, the total amount excreted in the urine and the metabolite profiles differed among the subjects. It appears that adsorption (digestion) from the meat matrix, other foods in the diet, and genetic differences in metabolism may contribute to the variation. The four major metabolites that can be routinely assayed in the urine are N2 -OH-PhIP- N2 -glucuronide, PhIP- N2 -glucuronide, 4,-PhIP-glucuronide, and N2 -OH-PhIP- N3-glucuronide. This work is suited to investigate individual exposure and risk, especially for breast cancer, from these potent dietary mutagens. Environ. Mol. Mutagen. 39:112,118, 2002. Published 2002 Wiley-Liss, Inc. [source]

    Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1

    GENES TO CELLS, Issue 7 2005
    Takashi Sasayama
    Aurora-A is a centrosomal serine-threonine kinase that regulates mitosis. Over-expression of Aurora-A has been found in a wide range of tumors and has been implicated in oncogenic transformation. However, how Aurora-A over-expression contributes to promotion of carcinogenesis remains elusive. Immunohistochemical analysis of breast tumors revealed that over-expressed Aurora-A is not restricted to the centrosomes but is also found in the cytoplasm. This over-expressed Aurora-A appeared to be phosphorylated on Thr288, which is known to be required for its enzymatic activation. In analogy to Aurora-A's role in oocyte maturation and the early embryonic cell cycle, here we investigated whether ectopically over-expressed Aurora-A can similarly stimulate polyadenylation of mRNA in human somatic cultured cells by interacting with a human ortholog of cytoplasmic polyadenylation element binding protein, h-CPEB. In vitro experiments revealed that Aurora-A binds directly to, and phosphorylates, h-CPEB. We found that polyadenylation of mRNA tails of cyclin B1 and Cdk1 was synergistically stimulated when Aurora-A and h-CPEB were over-expressed, and they were further promoted in the presence of an Aurora-A activator Ajuba. Our results suggest a function of ectopically over-expressed Aurora-A that might be relevant for carcinogenesis. [source]

    Chromosome 8 BAC array comparative genomic hybridization and expression analysis identify amplification and overexpression of TRMT12 in breast cancer,

    GENES, CHROMOSOMES AND CANCER, Issue 7 2007
    Virginia Rodriguez
    Genomic changes in chromosome 8 are commonly observed in breast cancer cell lines and tumors. To fine map such genomic changes by comparative genomic hybridization (CGH), a high resolution (100 kb) chromosome 8 array that can detect single copy changes was developed using Phi29 DNA polymerase amplified BAC (bacterial artificial chromosome) DNA. The BAC array CGH resolved the two known amplified regions (8q21 and 8q24) of a breast cancer cell line (SKBR3) into nine separate regions including six amplicons and three deleted regions, all of which were verified by Fluorescence in situ hybridization. The extent of the gain/loss for each region was validated by qPCR. CGH was performed with a total of 8 breast cancer cell lines, and common regions of genomic amplification/deletion were identified by segmentation analysis. A 1.2-Mb region (125.3,126.5 Mb) and a 1.0-Mb region (128.1,129.1 Mb) in 8q24 were amplified in 7/8 cell lines. A global expression analysis was performed to evaluate expression changes associated with genomic amplification/deletion: a novel gene, TRMT12 (at 125.5 Mb), amplified in 7/8 cell lines, showed highest expression in these cell lines. Further analysis by RT-qPCR using RNA from 30 breast tumors showed that TRMT12 was overexpressed >2 fold in 87% (26/30) of the tumors. TRMT12 is a homologue of a yeast gene encoding a tRNA methyltransferase involved in the posttranscriptional modification of tRNAPhe, and exploring the biological consequence of its altered expression, may reveal novel pathways in tumorigenesis. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. Published 2007 Wiley-Liss, Inc. [source]

    Co-amplification of 8p12 and 11q13 in breast cancers is not the result of a single genomic event

    GENES, CHROMOSOMES AND CANCER, Issue 5 2007
    Anna L. Paterson
    Epithelial cancers frequently have multiple amplifications, and particular amplicons tend to occur together. These co-amplifications have been suggested to result from amplification of pre-existing junctions between two chromosomes, that is, translocation junctions. We investigated this hypothesis for two amplifications frequent in breast cancer, at 8p12 and 11q13, which had been reported to be associated in Southern blot studies. We confirmed that both genomic amplification and expression of genes was correlated between the frequently-amplified regions of 8p and 11q, in array CGH and microarray expression data, supporting the importance of co-amplification. We examined by FISH the physical structure of co-amplifications that we had identified by array CGH, in five breast cancer cell lines (HCC1500, MDA-MB-134, MDA-MB-175, SUM44, and ZR-75-1), four breast tumors, and a pancreatic cancer cell line (SUIT2). We found a variety of arrangements: amplification of translocation junctions; entirely independent amplification of the two regions on separate chromosomes; and separate amplification of 8p and 11q sequences in distinct sites on the same rearranged chromosome. In this last arrangement, interphase nuclei often showed intermingling of FISH signals from 8p12 and 11q13, giving a false impression that the sequences were interdigitated. We conclude that co-amplification of the main 8p and 11q amplicons in breast tumors is not usually the result of a preceding translocation event but most likely reflects selection of clones that have amplified both loci. This article contains supplementary material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. © 2007 Wiley-Liss, Inc. [source]

    Profile of differentially expressed genes after transfer of chromosome 17 into the breast cancer cell line CAl51

    GENES, CHROMOSOMES AND CANCER, Issue 3 2005
    Christiane Klebig
    Previous studies have shown that transfer of chromosome 17 suppresses the tumorigenic phenotype of the breast cancer cell line CAL51, suggesting the presence of putative tumor suppressor genes on this chromosome. Suppression subtractive hybridization and oligonucleotide microarray analyses were performed to identify differentially expressed genes in nontumorigenic microcell hybrids, CAL/17-1 and CAL/17-3, when compared with CAL51 cells. In total, 263 differentially expressed transcripts were associated with these phenotypes. Of these, a high percentage is involved in various biological processes associated with tumorigenesis, including DNA-dependent regulation of transcription, regulation of cell cycle, signal transduction, and cell proliferation. Microarray analysis of selected chromosome 17 genes in a series of 25 human primary breast tumors showed associations with clinicopathologic parameters of the tumors. Of these genes, TOB1 (transducer of ERBB2) was selected for further expression analysis. Using RT-PCR and immunohistochemical staining of tissue microarrays, we could reveal a differential mRNA and protein expression of TOB1 in the majority of breast tumors and lymph node metastases compared with normal breast tissues, indicating a potential role of this protein in breast tumorigenesis. © 2005 Wiley-Liss, Inc. [source]

    PIK3CA cancer mutations display gender and tissue specificity patterns,

    HUMAN MUTATION, Issue 2 2008
    Silvia Benvenuti
    Abstract The occurrence of oncogenic alleles can display striking tissue specificity. For example KRAS mutations are very frequent in pancreatic cancers but relatively rare in melanomas. The opposite is true for BRAF mutations. Somatic mutations in the gene encoding for the phosphatidylinositol 3-kinase (PI3KCA) catalytic subunit, PIK3CA, occur at high frequency in many solid cancers. We have examined whether PI3K oncogenic mutations (exons 9 and 20) might exhibit gender and/or tissue specificity. By examining large cohorts of breast and colorectal cancers affecting both men and women we found that the pattern of PIK3CA mutations is distinctive. In colorectal cancers, PIK3CA (but not KRAS, APC, or TP53) mutations display a gender bias occurring at higher frequencies in women. We also found that male breast cancers display PIK3CA mutations at an overall frequency similar to that observed in female breast tumors. In male breast cancers, however, PIK3CA mutations are found mainly in exon 20. We conclude that PI3KCA mutations affecting exons 9 and 20 display gender- and tissue-specific patterns, thus suggesting that the different amino acid changes could exert distinct functional effects on the oncogenic properties of this enzyme. Furthermore, we propose that sexual dimorphisms and tissue specific factors might directly or indirectly influence the occurrence of PI3KCA cancer alleles. Hum Mutat 29(2), 284,288, 2008. © 2007 Wiley-Liss, Inc. [source]

    BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer

    INTERNATIONAL JOURNAL OF CANCER, Issue 7 2010
    Ali Naderi
    Abstract We have recently demonstrated that BEX2 is differentially expressed in primary breast tumors and BEX2 expression is required for the Nerve Growth factor inhibition of ceramide-induced apoptosis in breast cancer. In this study we investigate the functional role of BEX2 in the survival and growth of breast cancer cells. We demonstrate that BEX2 downregulation induces mitochondrial apoptosis and sensitizes breast cancer cells to the pro-apoptotic effects of ceramide, doxorubicin and staurosporine. In addition, BEX2 overexpression protects the breast cancer cells against mitochondrial apoptosis. We show that this effect of BEX2 is mediated through the modulation of Bcl-2 protein family, which involves the positive regulation of anti-apoptotic member Bcl-2 and the negative regulation of pro-apoptotic members BAD, BAK1 and PUMA. Moreover, our data suggests that BEX2 expression is required for the normal cell cycle progression during G1 in breast cancer cells through the regulation of cyclin D1 and p21. To further support the significance of BEX2 in the pathogenesis of breast cancer we demonstrate that BEX2 overexpression is associated with a higher activation of the Bcl-2/NF-,B pathway in primary breast tumors. Furthermore, we show that BEX2 downregulation results in a higher expression and activity of protein phosphatase 2A. The modulation of protein phosphatase 2A, which is also known to mediate the cellular response to ceramide, provides a possible mechanism to explain the BEX2-mediated cellular effects. This study demonstrates that BEX2 has a significant role in the regulation of mitochondrial apoptosis and G1 cell cycle in breast cancer. [source]

    Identification of prospective factors promoting osteotropism in breast cancer: a potential role for CITED2

    INTERNATIONAL JOURNAL OF CANCER, Issue 4 2010
    Wen Min Lau
    Abstract Breast cancer metastases develop in the bone more frequently than any other site and are a common cause of morbidity in the form of bone pain, pathological fractures, nerve compression and life-threatening hypercalcemia. Despite ongoing research efforts, the molecular and cellular mechanisms that regulate breast cancer cell homing to and colonization of the bone as well as resultant pathological bone alteration remain poorly understood. To identify key mediators promoting breast cancer metastasis to bone, we utilized an immunocompetent, syngeneic murine model of breast cancer metastasis employing the mammary tumor cell line NT2.5. Following intracardiac injection of NT2.5 cells in neu-N mice, metastases developed in the bone, liver and lung, closely mimicking the anatomical distribution of metastases in patients with breast cancer. Using an in vivo selection process, we established NT2.5 sublines demonstrating an enhanced ability to colonize the bone and liver. Genome-wide cDNA microarray analysis comparing gene expression between parental NT2.5 cells and established sublines revealed both known and novel mediators of bone metastasis and osteolysis, including the transcriptional co-activator CITED2. In further studies, we found that expression of CITED2 was elevated in human primary breast tumors and bone metastasis compared to normal mammary epithelium and was highest in breast cancer cell lines that cause osteolytic bone metastasis in animal models. In addition, reducing CITED2 expression in NT2.5 cells inhibited the establishment of bone metastasis and osteolysis in vivo, suggesting a potential role for CITED2 in promoting breast cancer bone metastasis. [source]

    Methylation of cystatin M promoter is associated with unfavorable prognosis in operable breast cancer

    INTERNATIONAL JOURNAL OF CANCER, Issue 12 2009
    Magdalini Kioulafa
    Abstract The methylation status of cystatin M (CST6) gene in breast tumors was investigated and its prognostic significance as a novel breast cancer biomarker was evaluated. Using methylation-specific PCR (MSP), CST6 promoter methylation was examined in 134 formalin fixed paraffin-embedded tissues (FFPEs): 10 pairs of breast tumors and their surrounding normal tissues, 10 breast fibroadenomas, 11 normal breast tissues and 93 breast tumors. Methylation of CST6 promoter was observed in 2/21 (9.5%) noncancerous breast tissues, 1/10 (10%) benign breast tumors (fibroadenomas) and 52 (55.9%) operable breast cancer tumor samples. CST6 was rarely methylated in the normal tissue surrounding the tumor (10%). During the follow-up period, 24 (25.8%) patients relapsed and 19 (20.4%) died. CST6 methylation was detected in 19 (79.2%) of patients who relapsed and in 15 (78.9%) of patients who died. Disease-free-interval (DFI) and overall survival (OS) were significantly associated with CST6 promoter methylation (p = 0.004 and p = 0.001 respectively). Multivariate analysis revealed that CST6 methylation is an independent prognostic factor for DFI (HR = 3.484; 95% CI: 1.155,10.511; p = 0.027). and OS (HR = 9.190; 95% CI: 1.989,42.454; p = 0.004). CST6 promoter methylation status in tumor cells seems to provide important prognostic information in operable breast cancer and merits to be further evaluated and validated in a larger cohort of patients. © 2009 UICC [source]

    Detection of different tumor growth kinetics in single transgenic mice with oncogene-induced mammary carcinomas by flat-panel volume computed tomography

    INTERNATIONAL JOURNAL OF CANCER, Issue 1 2009
    Katharina Jannasch
    Abstract Transgenic mouse models offer an excellent opportunity for studying the molecular basis of cancer development and progression. Here we applied flat-panel volume computed tomography (fpVCT) to monitor tumor progression as well as the development of tumor vasculature in vivo in a transgenic mouse model for oncogene-induced mammary carcinogenesis (WAP-T mice). WAP-T mice develop multiple mammary carcinomas on oncogene induction within 3 to 5 months. Following induction, 3-dimensional fpVCT data sets were obtained by serial single scans of entire mice in combination with iodine containing contrast agents and served as basis for precise measurements of tumor volumes. Thereby, we were able to depict tumors within the mammary glands at a very early stage of the development. Tumors of small sizes (0.001 cm3) were detected by fpVCT before being palpable or visible by inspection. The capability to determine early tumor onset combined with longitudinal noninvasive imaging identified diverse time points of tumor onset for each mammary carcinoma and different tumor growth kinetics for multiple breast carcinomas that developed in single mice. Furthermore, blood supply to the breast tumors, as well as blood vessels around and within the tumors, were clearly visible over time by fpVCT. Three-dimensional visualization of tumor vessels in high resolution was enhanced by the use of a novel blood pool contrast agent. Here, we demonstrate by longitudinal fpVCT imaging that mammary carcinomas develop at different time points in each WAP-T mouse, and thereafter show divergent growth rates and distinct vascularization patterns. © 2009 UICC [source]

    Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: Implication for breast cancer osteolytic bone metastases

    INTERNATIONAL JOURNAL OF CANCER, Issue 5 2008
    Guojun Bu
    Abstract Most breast cancer metastases in bone form osteolytic lesions, but the mechanisms of tumor-induced bone resorption and destruction are not fully understood. Although it is well recognized that Wnt/,-catenin signaling is important for breast cancer tumorigenesis, the role of this pathway in breast cancer bone metastasis is unclear. Dickkopf1 (Dkk1) is a secreted Wnt/,-catenin antagonist. In the present study, we demonstrated that activation of Wnt/,-catenin signaling enhanced Dkk1 expression in breast cancer cells and that Dkk1 overexpression is a frequent event in breast cancer. We also found that human breast cancer cell lines that preferentially form osteolytic bone metastases exhibited increased levels of Wnt/,-catenin signaling and Dkk1 expression. Moreover, we showed that breast cancer cell-produced Dkk1 blocked Wnt3A-induced osteoblastic differentiation and osteoprotegerin (OPG) expression of osteoblast precursor C2C12 cells and that these effects could be neutralized by a specific anti-Dkk1 antibody. In addition, we found that breast cancer cell conditioned media were able to block Wnt3A-induced NF-kappaB ligand reduction in C2C12 cells. Finally, we demonstrated that conditioned media from breast cancer cells in which Dkk1 expression had been silenced via RNAi were unable to block Wnt3A-induced C2C12 osteoblastic differentiation and OPG expression. Taken together, these results suggest that breast cancer-produced Dkk1 may be an important mechanistic link between primary breast tumors and secondary osteolytic bone metastases. © 2008 Wiley-Liss, Inc. [source]

    On the dynamics of breast tumor development in women carrying germline BRCA1 and BRCA2 mutations

    INTERNATIONAL JOURNAL OF CANCER, Issue 8 2008
    Richard Simon
    Abstract We used mathematical models to analyze the age-incidence curve of breast carcinoma for individuals carrying a germline mutation in the BRCA1 or BRCA2 gene locus. Although many genomic abnormalities have been identified in breast tumors, we found that a two-stage model fit the data well. A one-hit model was not, however, consistent with the data. The results supported the hypothesis that the first hit represents loss of the wild type BRCA1 or BRCA2 allele as this occurs at a rate very similar to that for loss of the wild-type RB allele in retinoblastoma. Loss of the wild-type BRCA1 or BRCA2 allele appears to destabilize the genome as the second event occurs at a much higher rate. The second event is "rate limiting" in the sense that its occurrence is constrained by the limited number of intermediate cells with doubly mutated BRCA1 or BRCA2 alleles. The second event may not be unique, however. Loss of the wild-type BRCA allele appears to result in an increased rate for subsequent genomic events. A second event increasing proliferation of the partially malignant intermediate clone may lead inexorably to production and selection of cells with additional mutations in genes that facilitate tumor progression. © 2007 Wiley-Liss, Inc. [source]

    Thermographic assessment of tumor growth in mouse xenografts

    INTERNATIONAL JOURNAL OF CANCER, Issue 5 2007
    Chengli Song
    Abstract In human breast tumors, a 1,2°C increase in skin surface temperature is usually observed at the periphery; it has been proposed that this change is due to the hypervascularity and increased blood flow resulting from tumor-associated angiogenesis. Here we tested the hypothesis that thermal imaging might represent a useful adjunctive technique in monitoring the growth dynamics of human tumor xenografts. Xenografts were established in immunocomprised nude mice using MDA-MB-231 or MCF7 breast cancer cells. We exploited the inherent noncontact and noninvasive advantages of infrared thermography to detect skin surface temperature changes. Continuous thermographic investigation was performed to detect and monitor tumor growth in vivo and high resolution digital images were analyzed to measure the tumor temperature dynamics. In contrast to the skin temperature increases associated with human breast cancer, a consistent temperature decrease was found in the xenograft mice. In one case, a smaller secondary tumor, otherwise undetectable, was clearly evident by thermal imaging. The tumors were cooler than the surrounding tissue with a maximum temperature reduction of 1.5°C for MDA-MB-231 tumor and 3°C for MCF7 tumors observed on day 14. In addition, the temperature of the xenograft tumors decreased progressively as they grew throughout the observation period. It was demonstrated that thermographic imaging could detect temperature changes as small as 0.1°C on the skin surface at an early stage of tumor development. The findings of the study indicate that thermographic imaging might have considerable potential in monitoring human tumor xenografts and their response to anticancer drugs. © 2007 Wiley-Liss, Inc. [source]

    Germline mutations 657del5 of the NBS1 gene contribute significantly to the incidence of breast cancer in Central Poland

    INTERNATIONAL JOURNAL OF CANCER, Issue 2 2006
    Jan Steffen
    Abstract Recent studies have demonstrated that heterozygous carriers of the NBS1 657del5 mutation have an increased risk for familial and bilateral breast cancer, but similar studies in consecutive breast cancer patients were inconclusive. Here, in a study of 562 nonselected breast cancer patients from Central Poland, we found 11 (1.96%) 657del5 mutation carriers vs. 3.47 expected (OR 3.21, 95%CI: 1.36,7.61, p = 0.0107) and only 9 (1.6%) carriers of the 5382insC mutation of the BRCA1 gene, most frequently found among breast cancer patients in Poland. No carriers of R215W, another pathogenic mutation of the NBS1 gene, were found in the present study. All carriers of the 657del5 mutation had sporadic breast tumors while 5 of 9 5382insC carriers had a family history of breast/ovarian cancer or bilateral breast carcinoma. In the pooled group of patients from the present and our previous study, carried out also in patients from Central Poland, we obtained the following risk estimates (OR) for 657del5 carriers, as related to the age at breast cancer diagnosis: <40 years: 8.36; (95%CI: 2.57,27.27) p = 0.0003; <50 years: 4.27 (95%CI: 1.67,10.89) p = 0.003; ,50 years: 2.40 (95%CI: 0.91,6.35) p = 0.1250; all ages: 3.13 (95% CI: 1.40,7.00) p = 0.0066. These findings demonstrate conclusively that NBS1 657del5 mutation carriers have a significantly, though moderately increased, age-related risk of breast cancer, and imply that in populations with a high 657del5 carrier frequency this mutation may contribute substantially to the overall incidence of breast cancer, particularly in younger age groups. © 2006 Wiley-Liss, Inc. [source]

    Frequent amplification and overexpression of CCND1 in male breast cancer

    INTERNATIONAL JOURNAL OF CANCER, Issue 6 2004
    Maarit Bärlund
    Abstract Genetic events underlying the pathogenesis of breast cancer have been studied extensively and several clinically significant markers have been identified. For example, amplification and overexpression of the ERBB2 oncogene is associated with poor prognosis in breast cancer and ERBB2 serves as a target for antibody-based therapy. Current knowledge on the pathogenesis of male breast cancer (MBC) is limited. The purpose of our study was to investigate the potential relevance of a series of genes known to be amplified in female breast cancer (FBC) in a the development and pathogenesis of MBC. To this end, we applied fluorescence in situ hybridization and immunohistochemistry to the analysis of 128 breast tumors from males. Amplification of ERBB2, MYC, PPM1D and ZNF217 was detected rarely (1,2% of tumors) indicating a considerably lower amplification frequency than in FBC. CCND1 amplification was observed in 12% of cases, being in good concordance with findings from FBC. In addition, CCND1 overexpression was detected in 63% of tumors and was associated with ER positivity (p < 0.0001). Our results indicate distinct differences in the genetic basis of MBC and FBC and suggest that marked differences exist in the pathogenesis of these diseases. The lack of ERBB2 involvement was especially unexpected and implies that ERBB2 -targeted therapies are unlikely to be beneficial in MBC. Furthermore, the high frequency of hormone receptor positivity and the association between ER positivity and CCND1 overexpression supports the notion that hormonal regulation is likely to be essential for the development of MBC. © 2004 Wiley-Liss, Inc. [source]

    Increased expression of the mannose 6-phosphate/insulin-like growth factor-II receptor in breast cancer cells alters tumorigenic properties in vitro and in vivo

    INTERNATIONAL JOURNAL OF CANCER, Issue 4 2003
    Jason S. Lee
    Abstract The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF-IIR) is thought to act as a suppressor of tumor growth by binding the mitogenic peptide IGF-II and modulating its extracellular levels via degradation. This receptor has been found to be absent or nonfunctional in a high proportion of breast tumors as a result of LOH and mutation of the gene. In our study, we have examined the effect of increasing expression of M6P/IGF-IIR on breast cancer cell tumorigenicity. MDA-MB-231 breast cancer cells stably transfected with M6P/IGF-IIR cDNA exhibited not only a greatly reduced ability to form tumors but also a markedly reduced growth rate in nude mice. In vitro, increased M6P/IGF-IIR expression resulted in 2-fold reduced uptake of IGF-II and was associated with reduced cellular invasiness and motility. Cells with increased M6P/IGF-IIR expression exhibited reduced phosphorylation of IGF-I receptor and p44/42 MAPK compared to vector transfectants, or wild-type MDA-MB-231 cells. These results therefore suggest that M6P/IGF-IIR levels can modulate breast cancer cell tumorigenicity by a mechanism that may involve altered IGF-I receptor signaling. © 2003 Wiley-Liss, Inc. [source]

    Detection of bone marrow-disseminated breast cancer cells using an RT-PCR assay of MUC5B mRNA

    INTERNATIONAL JOURNAL OF CANCER, Issue 4 2003
    Nora Berois
    Abstract The evaluation of disseminated epithelial tumor cells in breast cancer patients has generated considerable interest due to its potential association with disease recurrence. Our work was performed to analyze the usefulness of 5 mucin genes expression (MUC2, MUC3, MUC5B, MUC6 and MUC7), using RT-PCR assays, to detect disseminated cancer cells in patients with operable breast cancer. The highest frequencies of positive RT-PCR tests in breast tumor extracts were observed for MUC5B (7/15) and MUC7 (5/12). The best specificity, negative results on all peripheral blood mononuclear (PBMN) cell samples from healthy donors, were shown for MUC2, MUC5B and MUC6 RT-PCR assays. Thus, we selected MUC5B as a target gene for further evaluation. Using a nested RT-PCR, MUC5B mRNA transcripts were detected in 16/31 primary breast tumors (but not in 36 samples of normal PBMN cells) and in the human MCF-7 breast cancer cell line but not in BT20, MDA, T47D and ZR-75 breast cancer cell lines, indicating that MUC5B mRNA is expressed in a population of breast cancer cells. Using this method, 9/46 patients (19.5%) who underwent curative surgery showed positive MUC5B mRNA in bone marrow aspirates obtained prior to surgery, including 5/24 patients (20.8%) with stage I or II breast cancer, without histopathologic lymph node involvement. These results indicate that MUC5B mRNA could be a specific marker applicable to the molecular diagnosis of breast cancer cell dissemination. A comparative evaluation between MUC5B mRNA, cytokeratin 19 (CK19) mRNA and carcinoembryonic antigen (CEA) mRNA in all bone marrow aspirates suggests a putative complementation for molecular detection of disseminated carcinoma cells. Considering that breast cancer is characterized by a great phenotypic heterogeneity, the use of multimarker approach could contribute to tumor cell detection in bone marrow and blood. © 2002 Wiley-Liss, Inc. [source]

    Rcl is a novel ETV1/ER81 target gene upregulated in breast tumors

    JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2008
    Sook Shin
    Abstract ETV1 (ER81) is a transcription factor that can be activated by HER2/Neu, a proto-oncoprotein often overexpressed in metastatic breast tumors. Here, we demonstrate that ETV1 downregulation suppresses proliferation of HER2/Neu-positive MDA-MB-231 breast cancer cells in vitro and tumor formation in vivo, proving for the first time the existence of a critical role of ETV1 in breast cancer cell physiology. A screen for novel ETV1 target genes hinted at Rcl, an enzyme involved in nucleotide metabolism. To characterize the human Rcl gene, we cloned its promoter and found that ETV1 and HER2/Neu cooperated in activating the Rcl promoter, whereas a dominant-negative ETV1 molecule suppressed the Rcl promoter. Moreover, ETV1 and HER2/Neu synergized to upregulate the endogenous Rcl gene. ETV1 also bound to the Rcl promoter in vivo, indicating that Rcl is a bona fide target gene of ETV1. Hybridization of Rcl cDNA to a breast cancer array revealed that Rcl is overexpressed in ,40% of all breast tumors. Importantly, its expression significantly escalates with increasing tumor grade, strongly implicating that Rcl contributes to breast tumorigenesis. Since joint overexpression of Rcl with vascular endothelial growth factor, another target gene of ETV1, has been shown to induce tumor formation, Rcl may be one crucial effector of ETV1 and HER2/Neu in breast tumors. Furthermore, given its expression pattern and enzymatic function in nucleotide metabolism, Rcl presents itself as a novel target in breast cancer therapy via modulation of its activity by small molecule drugs. J. Cell. Biochem. 105: 866,874, 2008. © 2008 Wiley-Liss, Inc. [source]