Skip to main content
Erschienen in: Annals of Surgical Oncology 8/2009

01.08.2009 | Breast Oncology

Unraveling Breast Cancer Heterogeneity Through Transcriptomic and Epigenomic Analysis

verfasst von: Frank A. Orlando, MD, Kevin D. Brown, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 8/2009

Einloggen, um Zugang zu erhalten

Abstract

Breast cancer diversity is histologically evident as various proliferative benign lesions, in situ carcinomas, and invasive carcinomas that may develop into distant metastases. Breast tumor molecular subtypes have been defined by genome-wide expression microarray technology and reveal associations between genetic alterations and the malignant phenotype. Early work has been conducted to use subtype-specific biomarkers to elucidate targeted treatment options early in the course of breast cancer progression. Additionally, DNA methylation is an epigenetic modification that contributes to breast cancer progression by transcriptionally silencing certain tumor suppressor genes. Among the genes characterized as targets for silencing are well-established tumor suppressors such as RASSF1A, RARB, SFN, and TGM2. Measuring elevated gene copy number and aberrant gene promoter methylation can further facilitate characterization of breast tumor molecular subtype; however, profiling of breast tumors based on epigenetic criteria has yet to be established. Epigenomic analysis has been investigated for clinical applicability, and it has great promise when used in combination with minimally invasive techniques for both diagnostic and prognostic purposes.
Literatur
1.
Zurück zum Zitat Tavassoli FA, Deville P. World Health Organization classification of tumours: pathology and genetics of tumours of the breast and female genital organs. Lyon: IARC Press;2003. Tavassoli FA, Deville P. World Health Organization classification of tumours: pathology and genetics of tumours of the breast and female genital organs. Lyon: IARC Press;2003.
2.
Zurück zum Zitat Pusztai L. Current status of prognostic profiling in breast cancer. Oncologist. 2008;13:350–60.PubMedCrossRef Pusztai L. Current status of prognostic profiling in breast cancer. Oncologist. 2008;13:350–60.PubMedCrossRef
3.
Zurück zum Zitat Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.PubMedCrossRef Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.PubMedCrossRef
4.
Zurück zum Zitat Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.PubMedCrossRef Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.PubMedCrossRef
5.
Zurück zum Zitat Sorlie T, Tibshirani R, Parker J, et al. Repeated observations of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100:8418–23.PubMedCrossRef Sorlie T, Tibshirani R, Parker J, et al. Repeated observations of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100:8418–23.PubMedCrossRef
6.
Zurück zum Zitat Sorlie T, Wang Y, Xiao C, et al. Distinct molecular mechanisms underlying clinically relelvant subtypes of breast cancer: gene expression analysis across three different platforms. BMC Genomics. 2006;7:127.PubMedCrossRef Sorlie T, Wang Y, Xiao C, et al. Distinct molecular mechanisms underlying clinically relelvant subtypes of breast cancer: gene expression analysis across three different platforms. BMC Genomics. 2006;7:127.PubMedCrossRef
7.
Zurück zum Zitat Weigelt B, Horlings HM, Kreike B, et al. Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol. 2008;216:141–50.PubMedCrossRef Weigelt B, Horlings HM, Kreike B, et al. Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol. 2008;216:141–50.PubMedCrossRef
8.
Zurück zum Zitat Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the carolina breast cancer study. JAMA. 2006;295:2492–502.PubMedCrossRef Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the carolina breast cancer study. JAMA. 2006;295:2492–502.PubMedCrossRef
9.
Zurück zum Zitat Fisher B, Dignam J, Bryant J, Wolmark N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the national surgical adjuvant breast and bowel project B-14 randomized trial. J Natl Cancer Inst. 2001;93:684–90.PubMedCrossRef Fisher B, Dignam J, Bryant J, Wolmark N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the national surgical adjuvant breast and bowel project B-14 randomized trial. J Natl Cancer Inst. 2001;93:684–90.PubMedCrossRef
10.
Zurück zum Zitat Forbes JF, Cuzick J, Buzdar A, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008;9:45–53.PubMedCrossRef Forbes JF, Cuzick J, Buzdar A, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008;9:45–53.PubMedCrossRef
11.
Zurück zum Zitat Sherene L, Haibe-Kains B, Desmedt C, et al. Predicting prognosis using molecular profiling in estrogen-positive breast cancer treated with tamoxifen. BMC Genomics. 2008;9:239.CrossRef Sherene L, Haibe-Kains B, Desmedt C, et al. Predicting prognosis using molecular profiling in estrogen-positive breast cancer treated with tamoxifen. BMC Genomics. 2008;9:239.CrossRef
12.
Zurück zum Zitat Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11:5678-85.PubMedCrossRef Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11:5678-85.PubMedCrossRef
13.
Zurück zum Zitat Carey LA, Dees EC, Sawyer L, et al. Triple-negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.PubMedCrossRef Carey LA, Dees EC, Sawyer L, et al. Triple-negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.PubMedCrossRef
14.
Zurück zum Zitat Rakha EA, Reis-Filho JS, Ellis IO. Basal-like breast cancer: a critical review. J Clin Oncol. 2008;26:2568–81.PubMedCrossRef Rakha EA, Reis-Filho JS, Ellis IO. Basal-like breast cancer: a critical review. J Clin Oncol. 2008;26:2568–81.PubMedCrossRef
15.
Zurück zum Zitat Rakha EA, El-Sayed ME, Green AR, et al. Breast carcinoma with basal differentiation: a proposal for pathology definition based on cytokeratin expression. Histopathology. 2007;50:434–8.PubMedCrossRef Rakha EA, El-Sayed ME, Green AR, et al. Breast carcinoma with basal differentiation: a proposal for pathology definition based on cytokeratin expression. Histopathology. 2007;50:434–8.PubMedCrossRef
16.
Zurück zum Zitat Rakha EA, El-Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer. Cancer. 2007;109:25–32.PubMedCrossRef Rakha EA, El-Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer. Cancer. 2007;109:25–32.PubMedCrossRef
17.
Zurück zum Zitat Nielsen TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74.PubMedCrossRef Nielsen TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74.PubMedCrossRef
18.
Zurück zum Zitat Cameron D, Casey M, Press M, et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008;112:207–9.CrossRef Cameron D, Casey M, Press M, et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008;112:207–9.CrossRef
19.
Zurück zum Zitat Burstein HJ, Storniolo AM, Fanco S, et al. A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer. Ann Oncol. 2008;19:1068–74.PubMedCrossRef Burstein HJ, Storniolo AM, Fanco S, et al. A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer. Ann Oncol. 2008;19:1068–74.PubMedCrossRef
20.
Zurück zum Zitat Lin A, Rugo HS. The role of trastuzumab in early stage breast cancer: current data and treatment recommendations. Curr Treat Options Oncol. 2007;8:47–60.PubMedCrossRef Lin A, Rugo HS. The role of trastuzumab in early stage breast cancer: current data and treatment recommendations. Curr Treat Options Oncol. 2007;8:47–60.PubMedCrossRef
21.
Zurück zum Zitat Frassoldati A, Guarneri V, Piacentini F, et al. Letrozole versus letrozole plus Lapatinib (GW572016) in hormone-sensitive, HER2-negative operable breast cancer: a double-blind, randomized, phase II study with biomarker evaluation (EGF109077-LAP107692/LETLOB). Clin Breast Cancer. 2008;8:97–100.PubMedCrossRef Frassoldati A, Guarneri V, Piacentini F, et al. Letrozole versus letrozole plus Lapatinib (GW572016) in hormone-sensitive, HER2-negative operable breast cancer: a double-blind, randomized, phase II study with biomarker evaluation (EGF109077-LAP107692/LETLOB). Clin Breast Cancer. 2008;8:97–100.PubMedCrossRef
22.
Zurück zum Zitat Kauraniemi P, Kallioniemi A. Activation of multiple cancer-associated genes at the ERBB2 amplicon in breast cancer. Endocr Relat Cancer. 2006;13:39–49.PubMedCrossRef Kauraniemi P, Kallioniemi A. Activation of multiple cancer-associated genes at the ERBB2 amplicon in breast cancer. Endocr Relat Cancer. 2006;13:39–49.PubMedCrossRef
23.
Zurück zum Zitat Somiari SB, Shriver CD, He J, et al. Global search for chromosomal abnormalities in infiltrating ductal carcinoma of the breast using array-comparative genomic hybridization. Cancer Genet Cytogenet. 2004;155:108–18.PubMedCrossRef Somiari SB, Shriver CD, He J, et al. Global search for chromosomal abnormalities in infiltrating ductal carcinoma of the breast using array-comparative genomic hybridization. Cancer Genet Cytogenet. 2004;155:108–18.PubMedCrossRef
24.
Zurück zum Zitat Gilbert JA, Goetz MP, Reynolds CA, et al. Molecular analysis of metaplastic breast carcinoma: high EGFR copy number via aneusomy. Mol Cancer Ther. 2008;7:944–51.PubMedCrossRef Gilbert JA, Goetz MP, Reynolds CA, et al. Molecular analysis of metaplastic breast carcinoma: high EGFR copy number via aneusomy. Mol Cancer Ther. 2008;7:944–51.PubMedCrossRef
25.
Zurück zum Zitat Stratford AL, Habibi G, Astanehe A, et al. Epidermal growth factor receptor (EGFR) is transcriptionally induced by the Y-box binding protein-1 (YB-1) and can be inhibited with Iressa in basal-like breast cancer, providing a potential target for therapy. Breast Cancer Res. 2007;9:R61.PubMedCrossRef Stratford AL, Habibi G, Astanehe A, et al. Epidermal growth factor receptor (EGFR) is transcriptionally induced by the Y-box binding protein-1 (YB-1) and can be inhibited with Iressa in basal-like breast cancer, providing a potential target for therapy. Breast Cancer Res. 2007;9:R61.PubMedCrossRef
26.
Zurück zum Zitat Holst F, Stahl PR, Ruiz C, et al. Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer. Nat Genet. 2007;39:655–60.PubMedCrossRef Holst F, Stahl PR, Ruiz C, et al. Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer. Nat Genet. 2007;39:655–60.PubMedCrossRef
28.
Zurück zum Zitat Ehrlich M. DNA methylation in cancer: too much, but also too little. Oncogene. 2002;21:5400–13.PubMedCrossRef Ehrlich M. DNA methylation in cancer: too much, but also too little. Oncogene. 2002;21:5400–13.PubMedCrossRef
29.
Zurück zum Zitat Ehrlich M. Cancer-linked DNA hypomethylation and its relationship to hypermethylation. Curr Top Microbiol Immunol. 2006;310:251–74.PubMedCrossRef Ehrlich M. Cancer-linked DNA hypomethylation and its relationship to hypermethylation. Curr Top Microbiol Immunol. 2006;310:251–74.PubMedCrossRef
30.
Zurück zum Zitat Hoffmann MJ, Schulz WA. Causes and consequences of DNA hypomethylation in human cancer. Biochem Cell Biol. 2005;83:296–321.PubMedCrossRef Hoffmann MJ, Schulz WA. Causes and consequences of DNA hypomethylation in human cancer. Biochem Cell Biol. 2005;83:296–321.PubMedCrossRef
31.
Zurück zum Zitat Zhang Y, Reinberg, D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev. 2001;15:2343–60.PubMedCrossRef Zhang Y, Reinberg, D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev. 2001;15:2343–60.PubMedCrossRef
33.
Zurück zum Zitat Fraga MF, Ballestar E, Villar-Garea A, et al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet. 2005;37:391–400.PubMedCrossRef Fraga MF, Ballestar E, Villar-Garea A, et al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet. 2005;37:391–400.PubMedCrossRef
34.
35.
Zurück zum Zitat Lin JC, Jeong S, Liang G, et al. Role of nucleosomal occupancy in the epigenetic silencing of the MLH1 CpG island. Cancer Cell. 2007;12:432–44.PubMedCrossRef Lin JC, Jeong S, Liang G, et al. Role of nucleosomal occupancy in the epigenetic silencing of the MLH1 CpG island. Cancer Cell. 2007;12:432–44.PubMedCrossRef
38.
Zurück zum Zitat Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3:415–28.PubMedCrossRef Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3:415–28.PubMedCrossRef
39.
40.
Zurück zum Zitat Robertson KD, Uzvolgyi E, Liang G, et al. The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors. Nucleic Acids Res. 1999;27:2291–8.PubMedCrossRef Robertson KD, Uzvolgyi E, Liang G, et al. The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors. Nucleic Acids Res. 1999;27:2291–8.PubMedCrossRef
41.
Zurück zum Zitat Fahrner JA, Eguchi S, Herman JG, Baylin SB. Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. Cancer Res. 2002;62:7213–8.PubMed Fahrner JA, Eguchi S, Herman JG, Baylin SB. Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. Cancer Res. 2002;62:7213–8.PubMed
42.
Zurück zum Zitat Kondo Y, Shen L, Issa JP. Critical role of histone methylation in tumor suppressor gene silencing in colorectal cancer. Mol Cell Biol. 2003;23:206–15.PubMedCrossRef Kondo Y, Shen L, Issa JP. Critical role of histone methylation in tumor suppressor gene silencing in colorectal cancer. Mol Cell Biol. 2003;23:206–15.PubMedCrossRef
43.
Zurück zum Zitat Fujisawa K, Maesawa C, Sato R, et al. Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas. Lab Invest. 2005;85:214–24.PubMedCrossRef Fujisawa K, Maesawa C, Sato R, et al. Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas. Lab Invest. 2005;85:214–24.PubMedCrossRef
44.
Zurück zum Zitat Ting AH, Schuebel KE, Herman JG, Baylin SB. Short double-stranded RNA induces transcriptional gene silencing in human cancer cells in the absence of DNA methylation. Nat Genet. 2005;37:906–10.PubMedCrossRef Ting AH, Schuebel KE, Herman JG, Baylin SB. Short double-stranded RNA induces transcriptional gene silencing in human cancer cells in the absence of DNA methylation. Nat Genet. 2005;37:906–10.PubMedCrossRef
45.
47.
Zurück zum Zitat Toyota M, Ahuja N, Ohe-Toyota M, et al. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA. 1999;96:8681–6.PubMedCrossRef Toyota M, Ahuja N, Ohe-Toyota M, et al. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA. 1999;96:8681–6.PubMedCrossRef
48.
Zurück zum Zitat Shen L, Toyota M, Kondo Y, et al. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proc Natl Acad Sci USA. 2007;104:18654–9.PubMedCrossRef Shen L, Toyota M, Kondo Y, et al. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proc Natl Acad Sci USA. 2007;104:18654–9.PubMedCrossRef
49.
Zurück zum Zitat Cheng YW, Pincas H, Bacolod MD, et al. CpG island methylator phenotype associates with low-degree chromosomal abnormalities in colorectal cancer. Clin Cancer Res. 2008;14:6005–13.PubMedCrossRef Cheng YW, Pincas H, Bacolod MD, et al. CpG island methylator phenotype associates with low-degree chromosomal abnormalities in colorectal cancer. Clin Cancer Res. 2008;14:6005–13.PubMedCrossRef
51.
Zurück zum Zitat Goel A, Nagasaka T, Arnold CN, et al. The CpG island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer. Gastroenterology. 2007;132:127–38.PubMedCrossRef Goel A, Nagasaka T, Arnold CN, et al. The CpG island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer. Gastroenterology. 2007;132:127–38.PubMedCrossRef
52.
Zurück zum Zitat Shaw RJ, Hall GL, Lowe D, et al. CpG island methylation phenotype (CIMP) in oral cancer: associated with a marked inflammatory response and less aggressive tumour biology. Oral Oncol. 2007;43:878–86.PubMedCrossRef Shaw RJ, Hall GL, Lowe D, et al. CpG island methylation phenotype (CIMP) in oral cancer: associated with a marked inflammatory response and less aggressive tumour biology. Oral Oncol. 2007;43:878–86.PubMedCrossRef
53.
Zurück zum Zitat Ueki T, Toyota M, Sohn T, et al. Hypermethylation of multiple genes in pancreatic adenocarcinoma. Cancer Res. 2000;60:1835–9.PubMed Ueki T, Toyota M, Sohn T, et al. Hypermethylation of multiple genes in pancreatic adenocarcinoma. Cancer Res. 2000;60:1835–9.PubMed
54.
Zurück zum Zitat Toyota M, Ahuja N, Suzuki H, et al. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res. 1999;59: 5438–42.PubMed Toyota M, Ahuja N, Suzuki H, et al. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res. 1999;59: 5438–42.PubMed
55.
Zurück zum Zitat Zhang C, Guo X, Jiang G, et al. CpG island methylator phenotype association with upregulated telomerase activity in hepatocellular carcinoma. Int J Cancer. 2008;123: 998–1004.PubMedCrossRef Zhang C, Guo X, Jiang G, et al. CpG island methylator phenotype association with upregulated telomerase activity in hepatocellular carcinoma. Int J Cancer. 2008;123: 998–1004.PubMedCrossRef
56.
Zurück zum Zitat Tanemura A, Terando AM, Sim MS, et al. CpG island methylator phenotype predicts progression of malignant melanoma. Clin Cancer Res. 2009;15: 1801–7.PubMedCrossRef Tanemura A, Terando AM, Sim MS, et al. CpG island methylator phenotype predicts progression of malignant melanoma. Clin Cancer Res. 2009;15: 1801–7.PubMedCrossRef
57.
Zurück zum Zitat Brock MV, Gou M, Akiyama Y, et al. Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma. Clin Cancer Res. 2003;9: 2912–9.PubMed Brock MV, Gou M, Akiyama Y, et al. Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma. Clin Cancer Res. 2003;9: 2912–9.PubMed
58.
Zurück zum Zitat Widschwendter M, Siegmund KD, Muller HM, et al. Association of breast cancer DNA methylation profiles with hormone status and response to tamoxifen. Cancer Res. 2004;64:3807–13.PubMedCrossRef Widschwendter M, Siegmund KD, Muller HM, et al. Association of breast cancer DNA methylation profiles with hormone status and response to tamoxifen. Cancer Res. 2004;64:3807–13.PubMedCrossRef
59.
Zurück zum Zitat Feng W, Shen L, Wen S, et al. Correlation between CpG methylation profiles and hormone receptor status in breast cancers. Breast Cancer Res. 2007;9:R57. Feng W, Shen L, Wen S, et al. Correlation between CpG methylation profiles and hormone receptor status in breast cancers. Breast Cancer Res. 2007;9:R57.
60.
Zurück zum Zitat Fiegl H, Millinger S, Goebel G, et al. Breast cancer DNA methylation profiles in cancer cells and tumor stroma: association with HER-2/neu status in primary breast cancer. Cancer Res. 2006;66:29–33.PubMedCrossRef Fiegl H, Millinger S, Goebel G, et al. Breast cancer DNA methylation profiles in cancer cells and tumor stroma: association with HER-2/neu status in primary breast cancer. Cancer Res. 2006;66:29–33.PubMedCrossRef
61.
Zurück zum Zitat Sunami E, Shinozaki M, Sim MS, et al. Estrogen receptor and HER2/neu status affect epigenetic differences of tumor-related genes in primary breast tumors. Breast Cancer Res. 2008;10:R46.PubMedCrossRef Sunami E, Shinozaki M, Sim MS, et al. Estrogen receptor and HER2/neu status affect epigenetic differences of tumor-related genes in primary breast tumors. Breast Cancer Res. 2008;10:R46.PubMedCrossRef
62.
Zurück zum Zitat Esteller M, Corn PG, Baylin SB, Herman JG. A gene hypermethylation profile of human cancer. Cancer Res. 2001;61:3225–9.PubMed Esteller M, Corn PG, Baylin SB, Herman JG. A gene hypermethylation profile of human cancer. Cancer Res. 2001;61:3225–9.PubMed
63.
Zurück zum Zitat Bae YK, Brown A, Garrett E, et al. Hypermethylation in histologically distinct classes of breast cancer. Clin Cancer Res. 2004;10:5998–6005.PubMedCrossRef Bae YK, Brown A, Garrett E, et al. Hypermethylation in histologically distinct classes of breast cancer. Clin Cancer Res. 2004;10:5998–6005.PubMedCrossRef
64.
Zurück zum Zitat Fackler MJ, McVeigh M, Evron E, et al. DNA methylation of RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma. Int J Cancer. 2003;107:970–5.PubMedCrossRef Fackler MJ, McVeigh M, Evron E, et al. DNA methylation of RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma. Int J Cancer. 2003;107:970–5.PubMedCrossRef
65.
Zurück zum Zitat Lehmann U, Langer F, Feist H, Glockner S, Hasemeier B, Kreipe H. Quantitative assessment of promoter hypermethylation during breast cancer development. Am J Pathol. 2002;160: 605–12.PubMed Lehmann U, Langer F, Feist H, Glockner S, Hasemeier B, Kreipe H. Quantitative assessment of promoter hypermethylation during breast cancer development. Am J Pathol. 2002;160: 605–12.PubMed
66.
Zurück zum Zitat Tommasi S, Karm DL, Wu X, et al. Methylation of homeobox genes is a frequent and early epigenetic event in breast cancer. Breast Cancer Res. 2009;11: R14.PubMedCrossRef Tommasi S, Karm DL, Wu X, et al. Methylation of homeobox genes is a frequent and early epigenetic event in breast cancer. Breast Cancer Res. 2009;11: R14.PubMedCrossRef
67.
Zurück zum Zitat Pinzone JJ, Stevenson H, Strobl JS, et al. Molecular and cellular determinates of estrogen receptor α expression. Mol Cell Biol. 2004;24:4605–12.PubMedCrossRef Pinzone JJ, Stevenson H, Strobl JS, et al. Molecular and cellular determinates of estrogen receptor α expression. Mol Cell Biol. 2004;24:4605–12.PubMedCrossRef
68.
Zurück zum Zitat Lapidus RG, Nass SJ, Butash KA, et al. Mapping of ER gene CpG island methylation by methylation-specific polymerase chain reaction. Cancer Res. 1998;58:2515–9.PubMed Lapidus RG, Nass SJ, Butash KA, et al. Mapping of ER gene CpG island methylation by methylation-specific polymerase chain reaction. Cancer Res. 1998;58:2515–9.PubMed
69.
Zurück zum Zitat Wei M, Xu J, Dignam J, et al. Estrogen receptor α, BRCA1, and FANCF promoter methylation occur in dintinct subsets of sporadic breast cancers. Breast Cancer Res Treat. 2008;111:113–20.PubMedCrossRef Wei M, Xu J, Dignam J, et al. Estrogen receptor α, BRCA1, and FANCF promoter methylation occur in dintinct subsets of sporadic breast cancers. Breast Cancer Res Treat. 2008;111:113–20.PubMedCrossRef
70.
Zurück zum Zitat Widschwendter M, Jones PA. DNA methylation and breast carcinogenesis. Oncogene. 2002;21:5462–82.PubMedCrossRef Widschwendter M, Jones PA. DNA methylation and breast carcinogenesis. Oncogene. 2002;21:5462–82.PubMedCrossRef
71.
Zurück zum Zitat Catteau A, Harris WH, Xu CF, et al. Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics. Oncogene. 1999;18:1957–65.PubMedCrossRef Catteau A, Harris WH, Xu CF, et al. Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics. Oncogene. 1999;18:1957–65.PubMedCrossRef
72.
Zurück zum Zitat Esteller M, Silva JM, Dominguez G, et al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst. 2000;92:564–9.PubMedCrossRef Esteller M, Silva JM, Dominguez G, et al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst. 2000;92:564–9.PubMedCrossRef
73.
Zurück zum Zitat Birgisdottir V, Stefansson OA, Bodvarsdottir SK, et al. Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer. Breast Cancer Res. 2006;8:R38.PubMedCrossRef Birgisdottir V, Stefansson OA, Bodvarsdottir SK, et al. Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer. Breast Cancer Res. 2006;8:R38.PubMedCrossRef
74.
Zurück zum Zitat Xu X, Gammon MD, Zhang Y, et al. BRCA1 promoter methylation is associated with increased mortality among women with breast cancer. Breast Cancer Res Treat. 2008 Jun 3. [Epub ahead of print] PMID: 18521744. Xu X, Gammon MD, Zhang Y, et al. BRCA1 promoter methylation is associated with increased mortality among women with breast cancer. Breast Cancer Res Treat. 2008 Jun 3. [Epub ahead of print] PMID: 18521744.
75.
Zurück zum Zitat Turner NC, Reis-Filho JS, Russell AM, et al. BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene. 2007;26:2126–32.PubMedCrossRef Turner NC, Reis-Filho JS, Russell AM, et al. BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene. 2007;26:2126–32.PubMedCrossRef
76.
Zurück zum Zitat Matros E, Wang ZC, Lodeiro G, et al. BRCA1 promoter methylation in sporadic breast tumors: relationship to gene expression profiles. Breast Cancer Res Treat. 2005;91:179–86.PubMedCrossRef Matros E, Wang ZC, Lodeiro G, et al. BRCA1 promoter methylation in sporadic breast tumors: relationship to gene expression profiles. Breast Cancer Res Treat. 2005;91:179–86.PubMedCrossRef
77.
Zurück zum Zitat Bertucci F, Finetti P, Cervera N, et al. Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. Cancer Res. 2006;66:4636–44.PubMedCrossRef Bertucci F, Finetti P, Cervera N, et al. Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. Cancer Res. 2006;66:4636–44.PubMedCrossRef
78.
Zurück zum Zitat Salomon-Vincent A, Gruel N, Lucchesi C, et al. Identification of typical medullary breast carcinoma as a genomic sub-group of basal-like carcinomas, a heterogeneous new molecular entity. Breast Cancer Res. 2007;9:R24.CrossRef Salomon-Vincent A, Gruel N, Lucchesi C, et al. Identification of typical medullary breast carcinoma as a genomic sub-group of basal-like carcinomas, a heterogeneous new molecular entity. Breast Cancer Res. 2007;9:R24.CrossRef
79.
Zurück zum Zitat Krop IE, Sgroi D, Porter DA, et al. HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells. Proc Natl Acad Sci USA. 2001;98:9796–801.PubMedCrossRef Krop IE, Sgroi D, Porter DA, et al. HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells. Proc Natl Acad Sci USA. 2001;98:9796–801.PubMedCrossRef
80.
Zurück zum Zitat Krop I, Maguire P, Lahti Domenici J, et al. Lack of HIN-1 methylation in BRCA1-linked and “BRCA1-like” breast tumors. Cancer Res. 2003;63:2024–27.PubMed Krop I, Maguire P, Lahti Domenici J, et al. Lack of HIN-1 methylation in BRCA1-linked and “BRCA1-like” breast tumors. Cancer Res. 2003;63:2024–27.PubMed
81.
Zurück zum Zitat Tisserand P, Fouquet C, Barrois M, et al. Lack of HIN-1 methylation defines specific breast tumor subtypes including medullary carcinoma of the breast and BRCA1-linked tumors. Cancer Biol Ther. 2003;2:559–3.PubMed Tisserand P, Fouquet C, Barrois M, et al. Lack of HIN-1 methylation defines specific breast tumor subtypes including medullary carcinoma of the breast and BRCA1-linked tumors. Cancer Biol Ther. 2003;2:559–3.PubMed
82.
Zurück zum Zitat Pageau GJ, Hall LL, Ganesan S, et al. The disappearing Barr body in breast and ovarian cancers. Nat Rev Cancer. 2007;7:628–33.PubMedCrossRef Pageau GJ, Hall LL, Ganesan S, et al. The disappearing Barr body in breast and ovarian cancers. Nat Rev Cancer. 2007;7:628–33.PubMedCrossRef
83.
84.
Zurück zum Zitat Richardson AL, Wang ZC, Nicolo AD, et al. X chromosome abnormalities in basal-like human breast cancer. Cancer Cell. 2006;9:121–32.PubMedCrossRef Richardson AL, Wang ZC, Nicolo AD, et al. X chromosome abnormalities in basal-like human breast cancer. Cancer Cell. 2006;9:121–32.PubMedCrossRef
85.
Zurück zum Zitat Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005;434:400–4.PubMedCrossRef Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005;434:400–4.PubMedCrossRef
86.
87.
88.
Zurück zum Zitat Pasquali L, Bedeir A, Ringquist S, et al. Quantification of CpG island methylation in progressive breast lesions from normal to invasive carcinoma. Cancer Lett. 2007;257:136–44.PubMedCrossRef Pasquali L, Bedeir A, Ringquist S, et al. Quantification of CpG island methylation in progressive breast lesions from normal to invasive carcinoma. Cancer Lett. 2007;257:136–44.PubMedCrossRef
89.
Zurück zum Zitat Lodygin D, Hermeking H. The role of epigenetic inactivation of 14-3-3σ in human cancer. Cell Res. 2005;15:237–46.PubMedCrossRef Lodygin D, Hermeking H. The role of epigenetic inactivation of 14-3-3σ in human cancer. Cell Res. 2005;15:237–46.PubMedCrossRef
90.
Zurück zum Zitat Umbricht CB, Evron E, Gabrielson E, et al. Hypermethylation of 14-3-3σ is an early event in breast cancer. Oncogene. 2001;20:3348–53.PubMedCrossRef Umbricht CB, Evron E, Gabrielson E, et al. Hypermethylation of 14-3-3σ is an early event in breast cancer. Oncogene. 2001;20:3348–53.PubMedCrossRef
91.
Zurück zum Zitat Widschwendter M, Berger J, Hermann M, et al. Methylation and silencing of the retinoic acid receptor-β2 gene in breast cancer. J Natl Cancer Inst. 2000;92:826–32.PubMedCrossRef Widschwendter M, Berger J, Hermann M, et al. Methylation and silencing of the retinoic acid receptor-β2 gene in breast cancer. J Natl Cancer Inst. 2000;92:826–32.PubMedCrossRef
92.
Zurück zum Zitat Baylin SB. DNA methylation and gene silencing in cancer. Nat Clin Pract Oncol. 2005;2:S4–11.PubMedCrossRef Baylin SB. DNA methylation and gene silencing in cancer. Nat Clin Pract Oncol. 2005;2:S4–11.PubMedCrossRef
93.
Zurück zum Zitat Bean GR, Scott V, Yee L, et al. Retinoic acid receptor-β2 promoter methylation in random periareolar fine needle aspiration. Cancer Epidemiol Biomarkers Prev. 2005;14:790–8.PubMedCrossRef Bean GR, Scott V, Yee L, et al. Retinoic acid receptor-β2 promoter methylation in random periareolar fine needle aspiration. Cancer Epidemiol Biomarkers Prev. 2005;14:790–8.PubMedCrossRef
94.
Zurück zum Zitat Abrahamson M, Alvarez-Fernandez M, Nathanson CM. Cystatins. Biochem Soc Symp. 2003;70:179–99.PubMed Abrahamson M, Alvarez-Fernandez M, Nathanson CM. Cystatins. Biochem Soc Symp. 2003;70:179–99.PubMed
95.
Zurück zum Zitat Ai L, Kim WJ, Kim TY, et al. Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression. Cancer Res. 2006;66:7899–909.PubMedCrossRef Ai L, Kim WJ, Kim TY, et al. Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression. Cancer Res. 2006;66:7899–909.PubMedCrossRef
96.
Zurück zum Zitat Ai L, Tao Q, Zhong S, et al. Inactivation of Mnt inhibitory factor-1 (WIF1) expression by epigenetic silencing is a common event in breast cancer. Carcinogenesis. 2006;27:1341–8.PubMedCrossRef Ai L, Tao Q, Zhong S, et al. Inactivation of Mnt inhibitory factor-1 (WIF1) expression by epigenetic silencing is a common event in breast cancer. Carcinogenesis. 2006;27:1341–8.PubMedCrossRef
97.
Zurück zum Zitat Ai L, Kim WJ, Demircan B, et al. The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer. Carcinogenesis. 2008;29:510–8.PubMedCrossRef Ai L, Kim WJ, Demircan B, et al. The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer. Carcinogenesis. 2008;29:510–8.PubMedCrossRef
98.
Zurück zum Zitat Verma A, Mehta K. Tissue transglutaminase-mediated chemoresistance in cancer cells. Drug Resist Updat. 2007;10:144–51.PubMedCrossRef Verma A, Mehta K. Tissue transglutaminase-mediated chemoresistance in cancer cells. Drug Resist Updat. 2007;10:144–51.PubMedCrossRef
99.
Zurück zum Zitat Droufakou S, Deshmane V, Roylance R, et al. Multiple ways of silencing E-cadherin gene expression in lobular carcinoma of the breast. Int J Cancer. 2001;92:404–8.PubMedCrossRef Droufakou S, Deshmane V, Roylance R, et al. Multiple ways of silencing E-cadherin gene expression in lobular carcinoma of the breast. Int J Cancer. 2001;92:404–8.PubMedCrossRef
100.
Zurück zum Zitat Lehmann U, Celikkaya G, Hasemeier B, et al. Promoter hypermethylation of the death-associated protine kinase gene in cancer is associated with the invasive lobular subtype. Cancer Res. 2002;62:6634–8.PubMed Lehmann U, Celikkaya G, Hasemeier B, et al. Promoter hypermethylation of the death-associated protine kinase gene in cancer is associated with the invasive lobular subtype. Cancer Res. 2002;62:6634–8.PubMed
101.
Zurück zum Zitat Masood S. Cytomorphology as a risk predictor: experience with fine needle aspiration biopsy, nipple fluid aspiration, and ductal lavage. Clin Lab Med. 2005;25:827–43.PubMedCrossRef Masood S. Cytomorphology as a risk predictor: experience with fine needle aspiration biopsy, nipple fluid aspiration, and ductal lavage. Clin Lab Med. 2005;25:827–43.PubMedCrossRef
102.
Zurück zum Zitat Evron E, Dooley WC, Umbricht CB, et al. Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR. Lancet. 2001;357:1335–6.PubMedCrossRef Evron E, Dooley WC, Umbricht CB, et al. Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR. Lancet. 2001;357:1335–6.PubMedCrossRef
103.
Zurück zum Zitat Dooley WC, Ljung BM, Veronesi U, et al. Ductal lavage for detection of cellular atypia in women at high risk for breast cancer. J Natl Cancer Inst. 2001;93:1624–32.PubMed Dooley WC, Ljung BM, Veronesi U, et al. Ductal lavage for detection of cellular atypia in women at high risk for breast cancer. J Natl Cancer Inst. 2001;93:1624–32.PubMed
104.
Zurück zum Zitat Visvanathan K, Santor D, Ali SZ, et al. The reliability of nipple aspirate and ductal lavage in women at increased risk for breast cancer – a potential tool for breast cancer risk assessment and biomarker evaluation. Cancer Epidemiol Biomarkers Prev. 2007;16:950–55.PubMedCrossRef Visvanathan K, Santor D, Ali SZ, et al. The reliability of nipple aspirate and ductal lavage in women at increased risk for breast cancer – a potential tool for breast cancer risk assessment and biomarker evaluation. Cancer Epidemiol Biomarkers Prev. 2007;16:950–55.PubMedCrossRef
105.
Zurück zum Zitat Krassenstein R, Sauter E, Dulaimi E, et al. Detection of breast cancer in nipple aspirate fluid by CpG island hypermethylation. Clin Cancer Res. 2004;10:28–32.PubMedCrossRef Krassenstein R, Sauter E, Dulaimi E, et al. Detection of breast cancer in nipple aspirate fluid by CpG island hypermethylation. Clin Cancer Res. 2004;10:28–32.PubMedCrossRef
106.
Zurück zum Zitat Fackler MJ, McVeigh M, Mehrotra J et al. Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer. Cancer Res. 2004;64:4442–52.PubMedCrossRef Fackler MJ, McVeigh M, Mehrotra J et al. Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer. Cancer Res. 2004;64:4442–52.PubMedCrossRef
107.
Zurück zum Zitat Fackler MJ, Malone K, Zhang Z, et al. Quantitative multiplex methylation-specific PCR analysis doubles detection of tumor cells in breast ductal fluid. Clin Cancer Res. 2006;12:3306–10.PubMedCrossRef Fackler MJ, Malone K, Zhang Z, et al. Quantitative multiplex methylation-specific PCR analysis doubles detection of tumor cells in breast ductal fluid. Clin Cancer Res. 2006;12:3306–10.PubMedCrossRef
108.
Zurück zum Zitat Euhus DM, Bu D, Ashfaq R, et al. Atypia and DNA methylation in nipple duct lavage in relation to predict breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2007;16:1812–21.PubMedCrossRef Euhus DM, Bu D, Ashfaq R, et al. Atypia and DNA methylation in nipple duct lavage in relation to predict breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2007;16:1812–21.PubMedCrossRef
109.
Zurück zum Zitat Lewis CM, Cler LR, Bu DW, et al. Promoter hypermethylation in benign breast epithelium in relation to predicted breast cancer risk. Clin Cancer Res. 2005;11:166–72.PubMed Lewis CM, Cler LR, Bu DW, et al. Promoter hypermethylation in benign breast epithelium in relation to predicted breast cancer risk. Clin Cancer Res. 2005;11:166–72.PubMed
110.
Zurück zum Zitat Euhus DM, Bu D, Milchgrub S, et al. DNA methylation in benign breast epithelium in relation to age and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17:1051–9.PubMedCrossRef Euhus DM, Bu D, Milchgrub S, et al. DNA methylation in benign breast epithelium in relation to age and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17:1051–9.PubMedCrossRef
111.
Zurück zum Zitat Bean GR, Ibarra Drendall C, Goldenberg VK, et al. Hypermethylation or the breast cancer-associated gene 1 promoter does not predict cytologic atypia of correlate with surrogate end points of breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2007;16:50–6.PubMedCrossRef Bean GR, Ibarra Drendall C, Goldenberg VK, et al. Hypermethylation or the breast cancer-associated gene 1 promoter does not predict cytologic atypia of correlate with surrogate end points of breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2007;16:50–6.PubMedCrossRef
112.
Zurück zum Zitat Baker JC, Ostrander JH, Lem S, et al. ESR1 promoter hypermethylation does not predict atypia in RPFNA nor persistent atypia after 12 months tamoxifen chemoprevention. Cancer Epidemiol Biomarkers Prev. 2008;17:1884–90.PubMedCrossRef Baker JC, Ostrander JH, Lem S, et al. ESR1 promoter hypermethylation does not predict atypia in RPFNA nor persistent atypia after 12 months tamoxifen chemoprevention. Cancer Epidemiol Biomarkers Prev. 2008;17:1884–90.PubMedCrossRef
113.
Zurück zum Zitat Jeronimo C, Costa I, Martins MC, et al. Detection of gene promoter hypermethylation in fine needle washings from breast lesions. Clin Cancer Res. 2003;9:3413–7.PubMed Jeronimo C, Costa I, Martins MC, et al. Detection of gene promoter hypermethylation in fine needle washings from breast lesions. Clin Cancer Res. 2003;9:3413–7.PubMed
114.
Zurück zum Zitat Pu RT, Laitala LE, Alli PM, et al. Methylation profiling of benign and malignant breast lesions and its application to cytopathology. Mod Pathol. 2003;16:1095–101.PubMedCrossRef Pu RT, Laitala LE, Alli PM, et al. Methylation profiling of benign and malignant breast lesions and its application to cytopathology. Mod Pathol. 2003;16:1095–101.PubMedCrossRef
115.
Zurück zum Zitat Jeronimo C, Monteiro P, Henrique R, et al. Quantitative hypermethylation of a small panel of genes augments the diagnostic accuracy in fine-needle aspirate washings of breast lesions. Breast Cancer Res Treat. 2008;109:27–34.PubMedCrossRef Jeronimo C, Monteiro P, Henrique R, et al. Quantitative hypermethylation of a small panel of genes augments the diagnostic accuracy in fine-needle aspirate washings of breast lesions. Breast Cancer Res Treat. 2008;109:27–34.PubMedCrossRef
116.
Zurück zum Zitat Dulaimi E, Hillinck J, Ibanez de Caceres I, et al. Tumor suppressor gene promoter hypermethylation in serum of breast cancer patients. Clin Cancer Res. 2004;10:6189–93.PubMedCrossRef Dulaimi E, Hillinck J, Ibanez de Caceres I, et al. Tumor suppressor gene promoter hypermethylation in serum of breast cancer patients. Clin Cancer Res. 2004;10:6189–93.PubMedCrossRef
117.
Zurück zum Zitat Muller HM, Widschwendter A, Fiegl H, et al. DNA methylation in serum of breast cancer patients: an independent prognostic marker. Cancer Res. 2003;63:7641–5.PubMed Muller HM, Widschwendter A, Fiegl H, et al. DNA methylation in serum of breast cancer patients: an independent prognostic marker. Cancer Res. 2003;63:7641–5.PubMed
118.
Zurück zum Zitat Martinez-Galan J, Torres B, Del Moral R, et al. Quantitative detection of methylated ESR1 and 14-3-3-sigma gene promoters in serum as candidate biomarkers for diagnosis of breast cancer and evaluation of treatment efficacy. Cancer Biol Ther. 2008;7:958–65.PubMedCrossRef Martinez-Galan J, Torres B, Del Moral R, et al. Quantitative detection of methylated ESR1 and 14-3-3-sigma gene promoters in serum as candidate biomarkers for diagnosis of breast cancer and evaluation of treatment efficacy. Cancer Biol Ther. 2008;7:958–65.PubMedCrossRef
119.
Zurück zum Zitat Snell C, Krypuy M, Wong EM, et al. BRCA1 promoter methylation in peripheral blood DNA of mutation negative familial breast cancer patients with a BRCA1 tumour phenotype. Breast Cancer Res. 2008;10:R12.PubMedCrossRef Snell C, Krypuy M, Wong EM, et al. BRCA1 promoter methylation in peripheral blood DNA of mutation negative familial breast cancer patients with a BRCA1 tumour phenotype. Breast Cancer Res. 2008;10:R12.PubMedCrossRef
Metadaten
Titel
Unraveling Breast Cancer Heterogeneity Through Transcriptomic and Epigenomic Analysis
verfasst von
Frank A. Orlando, MD
Kevin D. Brown, PhD
Publikationsdatum
01.08.2009
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 8/2009
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0500-y

Weitere Artikel der Ausgabe 8/2009

Annals of Surgical Oncology 8/2009 Zur Ausgabe

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Wie sieht der OP der Zukunft aus?

04.05.2024 DCK 2024 Kongressbericht

Der OP in der Zukunft wird mit weniger Personal auskommen – nicht, weil die Technik das medizinische Fachpersonal verdrängt, sondern weil der Personalmangel es nötig macht.

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Recycling im OP – möglich, aber teuer

02.05.2024 DCK 2024 Kongressbericht

Auch wenn sich Krankenhäuser nachhaltig und grün geben – sie tragen aktuell erheblich zu den CO2-Emissionen bei und produzieren jede Menge Müll. Ein Pilotprojekt aus Bonn zeigt, dass viele Op.-Abfälle wiederverwertet werden können.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.