Multidrug resistance in logally advanced breast cancer

Atalay, Mustafa Can
Breast cancer is the most frequently detected cancer among women. Early diagnosis leads to long term survival when the patients are treated with surgery, radiotherapy, chemotherapy, and hormone therapy. Unfortunately, advanced disease could still be encountered in some patients resulting in a poorer prognosis. The primary treatment modality is chemotherapy for this group of patients. Drug resistance is a serious problem resulting in the use of different drugs during chemotherapy and knowing the possibility of resistance before initiating first line chemotherapy may save time and money, and most importantly, may increase patient̕s survival. Therefore in this study, multidrug resistance is studied in locally advanced breast cancer patients. The breast tissues obtained from 25 patients both before and after chemotherapy were examined for drug resistance. Reverse transcriptase polymerase chain reaction was used for the detection of mdr1 and mrp1 gene expression. In addition, immunohistochemistry technique was used for P-glycoprotein and MRP1 detection. JSB-1 and QCRL-1 monoclonal antibodies were utilized to detect P-glycoprotein and MRP1, respectively. Five patients were unresponsive to chemotherapy. In four of these patients mdr1 gene expression was induced by chemotherapy where as the fifth patient initially had mdr1 gene expression. In addition, Pgp positivity was detected in 9 patients after chemotherapy. Both the induction of mdr1 gene expression (p<0.001) and Pgp positivity (p<0.001) during chemotherapy were significantly related with clinical response. On the other hand, mrp1 gene expression and MRP1 positivity were detected in 68% of the patients before the therapy. After chemotherapy, mrp1 expression increased to 84%. Although 80% of the clinically unresponsive patients had mrp1 gene expression, the relation between mrp1 expression and clinical drug response was


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The incidence of breast cancer is 1 in 8 among women. Usually loss of tumor suppressor genes and overexpression of proto-oncogenes are known to be involved during mammary tumorigenesis. USP32 (Ubiquitin Specific Protease 32) gene is located on chromosomal band 17q23, a region of amplification in breast cancer. Gene amplification is known to be a common mechanism in breast cancer cells, through which proto-oncogenes are overexpressed and contribute to tumor progression. Presence of multiple oncogene candidat...
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Akman, Begüm H; Erson Bensan, Ayşe Elif; Department of Biology (2007)
17q23 amplicon is one of the many chromosomal regions that undergo amplification in breast tumors. Such amplicons harbor proto-oncogenes that may be overexpressed due to gene amplifications. Copy number analysis in breast cancer cell lines and breast tumors identified several independently amplified regions within the 17q23 amplicon, suggesting that a number of genes are selected for amplification as they may independently contribute to tumor formation and progression. To characterize distinct amplicons on ...
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Multidrug resistance in locally advanced breast cancer
Atalay, Can; Gurhan, Ismet Deliloglu; Irkkan, Cigdem; Gündüz, Ufuk (2006-01-01)
Background: Advanced breast cancer cases can still be encountered resulting in poor prognosis. The primary treatment for these patients is chemotherapy, and multidrug resistance (MDR) is a serious obstacle in the treatment. Detecting drug resistance before first-line chemotherapy may increase the patient's survival. In this study, the role of MDR is evaluated in locally advanced breast cancer patients. Methods: Reverse transcriptase polymerase chain reaction was used for the detection of MDR genes, ABCB1 an...
Novel BRCA2 pathogenic genotype and breast cancer phenotype discordance in monozygotic triplets
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BRCA1/2 genes with high-penetrance are tumor suppressor and tumor susceptibility genes that play important roles in the homologous recombination mechanism in DNA repair and increase breast cancer risk. Variants in BRCA1 or BRCA2 are the main causes of familial and early-onset breast cancer. This study investigated pathogenic variant belonging to the BRCA2 gene splice region in monozygotic triplets. A 44-year-old woman was diagnosed with breast cancer when she was 32 years old. Her monozygotic sister had a h...
Citation Formats
M. C. Atalay, “Multidrug resistance in logally advanced breast cancer,” Ph.D. - Doctoral Program, Middle East Technical University, 2004.