Triple negative breast carcinoma and the basal phenotype: from expression profiling to clinical practice.
ABSTRACT Triple negative breast carcinomas (TNBCs) are a group of primary breast tumors with aggressive clinical behavior. Most TNBCs possess a basal phenotype (BP) and show varying degrees of basal cytokeratin and myoepithelial marker expression. The importance of recognizing these tumors came to light largely as the result of gene expression profiling studies that categorized breast cancer into 3 major groups. Two of these groups are defined by their respective expression of estrogen receptor and HER2. TNBCs represent a third group and are defined by negativity for hormone receptors and HER2. TNBCs currently lack effective targeted therapies and are frequently resistant to standard chemotherapeutic regimens. These tumors tend to occur in premenopausal women and members of specific ethnic groups and a subset are associated with heritable BRCA1 mutations. For patients with sporadic TNBCs and BP tumors, BRCA1 dysfunction seems to play a major role in the development and progression of disease. The pathologist's role in the diagnosis and characterization of TNBCs and BP tumors is currently being defined as we are acquiring knowledge of the biologic and genetic underpinnings that drive this heterogeneous group of diseases. This review will provide a historical prospective on TNBCs and tumors that express basal cytokeratins and myoepithelial makers. Additionally, we will discuss the molecular biologic, genetic and pathologic aspects of these tumors. Guidelines will be provided on how to best approach the diagnosis of these cases and on what input pathologists should provide clinicians to help develop optimal therapeutic and preventative strategies against this aggressive group of breast cancers.
SourceAvailable from: Natalya Volod'ko[Show abstract] [Hide abstract]
ABSTRACT: Over the last few years found that approximately 5–10% of breast cancer due to mutations in the genes BRCA1/2. Most of these hereditary cancers belong to the basal type is «triple negative» for receptor status. We describe a case ovarian cancer and breast cancer in patient B. Given the «triple » status tumors expressed genetic component (diagnosed 6 cases of malignant tumors of the maternal line), and molecular genetic data analysis (identified mutation in the gene 185 delAG BRCA1), it was recommended to neoadjuvant therapy based on platinum drugs. She received 5 cycles of palliative chemotherapy carboplatin (last 13.02.2012.) According to the CT scan after 3 cycles of chemotherapy found a partial regression of disease. At this time (October, 2012) the patient is under the supervision of oncologists.
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ABSTRACT: Background A pilot study was undertaken to find significance of vascular endothelial growth factor (VEGF) and cancer antigen (CA 15.3) in breast cancer patients.Materials and methods Total 70 patients with breast cancer were divided into triple negative breast cancer (TNBC) and non-TNBC depending on oestrogen receptors, progesterone receptors or HER-2/neu receptors status. Serum CA 15.3 and VEGF levels were evaluated with enzyme-linked immunosorbent assay at the time of diagnosis and were correlated with age, tumour size and stage of the disease in both the groups. Spearman's test was used to find the correlation.Results VEGF levels were found to be >400 pg/ml in 27 patients, 19 (54·33%) of them were TNBC and only 8 (22·87%) non-TNBC. Mean values of the VEGF were, 784·34 pg/ml in TNBC and 334·60 pg/ml non-TNBC patients, respectively. CA 15.3 level was found to be higher in non-TNBC group (60·72 U/ml) than in TNBC group (45·24 U/ml). In all patients significant correlation was found between serum CA 15.3 level and tumour size and stage of the disease. In non-TNBC patients significant correlation was seen between CA 15.3 values and stage of the disease, but VEGF had no correlation with any of the disease parameters. In TNBC patients, there was no correlation between CA 15.3 level and any of the disease parameters but VEGF showed a significant correlation with both tumour size and stage of the disease.Conclusion Expression profile of VEGF was high in TNBC than non-TNBC patients. VEGF serves to be a better biomarker as compared with CA 15.3 in TNBC patients.Journal of Radiotherapy in Practice 03/2013; 13(01):60-67. DOI:10.1017/S146039691200057X
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ABSTRACT: We have previously indicated that the ideal animal tumor model should mimic the human disease. This means that the investigator should be able to ascertain the influence of host factors on the initiation of tumorigenesis, mimic the susceptibility of tumor response based on age and reproductive history, and determine the response of the tumors induced to chemotherapy. The utilization of experimental models of mammary carcinogenesis in risk assessment requires that the influence of ovarian, pituitary, and placental hormones, among others, as well as overall reproductive events are taken into consideration, since they are important modifiers of the susceptibility of the organ to neoplastic development. Several species, such as rodents, dogs, cats, and monkeys, have been evaluated for these purposes; however, none of them fulfills all the criteria specified previously. Rodents, however, are the most widely used models; therefore, this work will concentrate on discussing the rat rodent model of mammary carcinogenesis. © 2014 by The Author(s).Toxicologic Pathology 02/2015; 43(2):145-170. DOI:10.1177/0192623314532036 · 1.92 Impact Factor