Evaluation of the prognostic role of centromere 17 gain and HER2/topoisomerase II alpha gene status and protein expression in patients with breast cancer treated with anthracycline-containing adjuvant chemotherapy: pooled analysis of two Hellenic Cooperative Oncology Group (HeCOG) phase III trials

BMC Cancer

George Fountzilas¹⁰  Urania Dafni⁵  Mattheos Bobos¹²  Vassiliki Kotoula¹³  Anna Batistatou⁸  Ioannis Xanthakis¹⁰  Christos Papadimitriou¹¹  Ioannis Kostopoulos¹³  Triantafillia Koletsa¹³  Eleftheria Tsolaki¹²  Despina Televantou¹²  Eleni Timotheadou¹⁰  Angelos Koutras¹⁴  George Klouvas¹⁵  Epaminontas Samantas⁹  Nikolaos Pisanidis¹  Charisios Karanikiotis⁷  Ioanna Sfakianaki¹⁰  Nicholas Pavlidis²  Helen Gogas⁶  Helena Linardou⁴  Konstantine T Kalogeras¹⁶  Dimitrios Pectasides³  Meletios A Dimopoulos¹¹ 

[1] Department of Medical Oncology, IKA Hospital, Thessaloniki, Greece

[2] Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece

[3] Oncology Section, Second Department of Internal Medicine, “Hippokration” Hospital, Athens, Greece

[4] First Department of Medical Oncology, “Metropolitan” Hospital, Athens, Greece

[5] Laboratory of Biostatistics, University of Athens School of Nursing, Athens, Greece

[6] First Department of Medicine, “Laiko” General Hospital, University of Athens School of Medicine, Athens, Greece

[7] Department of Medical Oncology, 424 Army General Hospital, Thessaloniki, Greece

[8] Department of Pathology, Ioannina University Hospital, Ioannina, Greece

[9] Third Department of Medical Oncology, “Agii Anargiri”, Cancer Hospital, Athens, Greece

[10] Department of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

[11] Department of Clinical Therapeutics, “Alexandra” Hospital, University of Athens School of Medicine, Athens, Greece

[12] Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

[13] Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

[14] Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece

[15] Second Department of Medical Oncology, “Metropolitan” Hospital, Athens, Greece

[16] Translational Research Section, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece

关键词: Breast cancer;    Taxanes;    Anthracyclines;    Adjuvant chemotherapy;    Predictive factors;    Prognostic factors;    TopoIIa;    TOP2A;    HER2;   

Others  :  1079827
DOI  :  10.1186/1471-2407-13-163

 received in 2012-11-21, accepted in 2013-03-20,  发布年份 2013

【 授权许可】

   
2013 Fountzilas et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics. CA Cancer J Clin 2009, 59(4):225-249.
• [2]La Vecchia C, Bosetti C, Lucchini F, Bertuccio P, Negri E, Boyle P, Levi F: Cancer mortality in Europe, 2000–2004, and an overview of trends since 1975. Ann Oncol 2010, 21(6):1323-1360.
• [3]Early Breast Cancer Trialists' Collaborative Group (EBCTCG): Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005, 365(9472):1687-1717.
• [4]Levine MN, Whelan T: Adjuvant chemotherapy for breast cancer–30 years later. N Engl J Med 2006, 355(18):1920-1922.
• [5]Smith I, Chua S: Medical treatment of early breast cancer. III: chemotherapy. Bmj 2006, 332(7534):161-162.
• [6]Doyle JJ, Neugut AI, Jacobson JS, Grann VR, Hershman DL: Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study. J Clin Oncol 2005, 23(34):8597-8605.
• [7]Hershman D, Neugut AI, Jacobson JS, Wang J, Tsai WY, McBride R, Bennett CL, Grann VR: Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy. J Natl Cancer Inst 2007, 99(3):196-205.
• [8]Thompson F, Emerson J, Dalton W, Yang JM, McGee D, Villar H, Knox S, Massey K, Weinstein R, Bhattacharyya A: Clonal chromosome abnormalities in human breast carcinomas. I. Twenty-eight cases with primary disease. Genes Chromosomes Cancer 1993, 7(4):185-193.
• [9]Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature 2006, 440(7087):1045-1049.
• [10]Botti C, Pescatore B, Mottolese M, Sciarretta F, Greco C, Di Filippo F, Gandolfo GM, Cavaliere F, Bovani R, Varanese A: Incidence of chromosomes 1 and 17 aneusomy in breast cancer and adjacent tissue: an interphase cytogenetic study. J Am Coll Surg 2000, 190(5):530-539.
• [11]Reinholz MM, Bruzek AK, Visscher DW, Lingle WL, Schroeder MJ, Perez EA, Jenkins RB: Breast cancer and aneusomy 17: implications for carcinogenesis and therapeutic response. Lancet Oncol 2009, 10(3):267-277.
• [12]Salido M, Tusquets I, Corominas JM, Suarez M, Espinet B, Corzo C, Bellet M, Fabregat X, Serrano S, Sole F: Polysomy of chromosome 17 in breast cancer tumors showing an overexpression of ERBB2: a study of 175 cases using fluorescence in situ hybridization and immunohistochemistry. Breast Cancer Res 2005, 7(2):26.
• [13]Dal Lago L, Durbecq V, Desmedt C, Salgado R, Verjat T, Lespagnard L, Ma Y, Veys I, Di Leo A, Sotiriou C: Correction for chromosome-17 is critical for the determination of true Her-2/neu gene amplification status in breast cancer. Mol Cancer Ther 2006, 5(10):2572-2579.
• [14]Hyun CL, Lee HE, Kim KS, Kim SW, Kim JH, Choe G, Park SY: The effect of chromosome 17 polysomy on HER-2/neu status in breast cancer. J Clin Pathol 2008, 61(3):317-321.
• [15]Vranic S, Teruya B, Repertinger S, Ulmer P, Hagenkord J, Gatalica Z: Assessment of HER2 gene status in breast carcinomas with polysomy of chromosome 17. Cancer 2011, 117(1):48-53.
• [16]Yeh IT, Martin MA, Robetorye RS, Bolla AR, McCaskill C, Shah RK, Gorre ME, Mohammed MS, Gunn SR: Clinical validation of an array CGH test for HER2 status in breast cancer reveals that polysomy 17 is a rare event. Mod Pathol 2009, 22(9):1169-1175.
• [17]Viale G: Be precise! The need to consider the mechanisms for CEP17 copy number changes in breast cancer. J Pathol 2009, 219(1):1-2.
• [18]Marchio C, Lambros MB, Gugliotta P, Di Cantogno LV, Botta C, Pasini B, Tan DS, Mackay A, Fenwick K, Tamber N: Does chromosome 17 centromere copy number predict polysomy in breast cancer? A fluorescence in situ hybridization and microarray-based CGH analysis. J Pathol 2009, 219(1):16-24.
• [19]Moelans CB, de Weger RA, van Diest PJ: Absence of chromosome 17 polysomy in breast cancer: analysis by CEP17 chromogenic in situ hybridization and multiplex ligation-dependent probe amplification. Breast Cancer Res Treat 2010, 120(1):1-7.
• [20]Tse CH, Hwang HC, Goldstein LC, Kandalaft PL, Wiley JC, Kussick SJ, Gown AM: Determining true HER2 gene status in breast cancers with polysomy by using alternative chromosome 17 reference genes: implications for anti-HER2 targeted therapy. J Clin Oncol 2011, 29(31):4168-4174.
• [21]Moelans CB, Reis-Filho JS, van Diest PJ: Implications of rarity of chromosome 17 polysomy in breast cancer. Lancet Oncol 2011, 12(12):1087-1089.
• [22]Bartlett JM, Munro AF, Dunn JA, McConkey C, Jordan S, Twelves CJ, Cameron DA, Thomas J, Campbell FM, Rea DW: Predictive markers of anthracycline benefit: a prospectively planned analysis of the UK National Epirubicin Adjuvant Trial (NEAT/BR9601). Lancet Oncol 2010, 11(3):266-274.
• [23]Pauletti G, Godolphin W, Press MF, Slamon DJ: Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. Oncogene 1996, 13(1):63-72.
• [24]Tanner M, Jarvinen P, Isola J: Amplification of HER-2/neu and topoisomerase IIalpha in primary and metastatic breast cancer. Cancer Res 2001, 61(14):5345-5348.
• [25]Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987, 235(4785):177-182.
• [26]Jarvinen TA, Liu ET: Simultaneous amplification of HER-2 (ERBB2) and topoisomerase IIalpha (TOP2A) genes–molecular basis for combination chemotherapy in cancer. Curr Cancer Drug Targets 2006, 6(7):579-602.
• [27]Hayes DF, Thor AD, Dressler LG, Weaver D, Edgerton S, Cowan D, Broadwater G, Goldstein LJ, Martino S, Ingle JN: HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 2007, 357(15):1496-1506.
• [28]Gennari A, Sormani MP, Pronzato P, Puntoni M, Colozza M, Pfeffer U, Bruzzi P: HER2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials. J Natl Cancer Inst 2008, 100(1):14-20.
• [29]Di Leo A, Larsimont D, Gancberg D, Jarvinen T, Beauduin M, Vindevoghel A, Michel J, Focan CH, Ries F, Gobert PH: HER-2 and topo-isomerase IIalpha as predictive markers in a population of node-positive breast cancer patients randomly treated with adjuvant CMF or epirubicin plus cyclophosphamide. Ann Oncol 2001, 12(8):1081-1089.
• [30]Konecny GE, Thomssen C, Luck HJ, Untch M, Wang HJ, Kuhn W, Eidtmann H, du Bois A, Olbricht S, Steinfeld D: Her-2/neu gene amplification and response to paclitaxel in patients with metastatic breast cancer. J Natl Cancer Inst 2004, 96(15):1141-1151.
• [31]Kellner U, Sehested M, Jensen PB, Gieseler F, Rudolph P: Culprit and victim – DNA topoisomerase II. Lancet Oncol 2002, 3(4):235-243.
• [32]Beser AR, Tuzlali S, Guzey D, Dolek Guler S, Hacihanefioglu S, Dalay N: HER-2, TOP2A and chromosome 17 alterations in breast cancer. Pathol Oncol Res 2007, 13(3):180-185.
• [33]Champoux JJ: DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem 2001, 70:369-413.
• [34]Ju BG, Lunyak VV, Perissi V, Garcia-Bassets I, Rose DW, Glass CK, Rosenfeld MG: A topoisomerase IIbeta-mediated dsDNA break required for regulated transcription. Science 2006, 312(5781):1798-1802.
• [35]Jarvinen TA, Tanner M, Barlund M, Borg A, Isola J: Characterization of topoisomerase II alpha gene amplification and deletion in breast cancer. Genes Chromosomes Cancer 1999, 26(2):142-150.
• [36]Knoop AS, Knudsen H, Balslev E, Rasmussen BB, Overgaard J, Nielsen KV, Schonau A, Gunnarsdottir K, Olsen KE, Mouridsen H: Retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. J Clin Oncol 2005, 23(30):7483-7490.
• [37]Schindlbeck C, Mayr D, Olivier C, Rack B, Engelstaedter V, Jueckstock J, Jenderek C, Andergassen U, Jeschke U, Friese K: Topoisomerase IIalpha expression rather than gene amplification predicts responsiveness of adjuvant anthracycline-based chemotherapy in women with primary breast cancer. Cancer Res Clin Oncol 2010, 136(7):1029-1037.
• [38]Simon RM, Paik S, Hayes DF: Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 2009, 101(21):1446-1452.
• [39]Fountzilas G, Skarlos D, Dafni U, Gogas H, Briasoulis E, Pectasides D, Papadimitriou C, Markopoulos C, Polychronis A, Kalofonos HP: Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol 2005, 16(11):1762-1771.
• [40]Fountzilas G, Dafni U, Gogas H, Linardou H, Kalofonos HP, Briasoulis E, Pectasides D, Samantas E, Bafaloukos D, Stathopoulos GP: Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00. Ann Oncol 2008, 19(5):853-860.
• [41]Gogas H, Dafni U, Karina M, Papadimitriou C, Batistatou A, Bobos M, Kalofonos HP, Eleftheraki AG, Timotheadou E, Bafaloukos D: Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial. Breast Cancer Res Treatment 2012, 132(2):609-619.
• [42]Fountzilas G, Dafni U, Bobos M, Batistatou A, Kotoula V, Trihia H, Malamou-Mitsi V, Miliaras S, Chrisafi S, Papadopoulos S: Differential response of immunohistochemically defined breast cancer subtypes to anthracycline-based adjuvant chemotherapy with or without paclitaxel. PLoS One 2012, 7(6):e37946.
• [43]Razis E, Bobos M, Kotoula V, Eleftheraki AG, Kalofonos HP, Pavlakis K, Papakostas P, Aravantinos G, Rigakos G, Efstratiou I: Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer. Breast Cancer Research Treat 2011, 128(2):447-456.
• [44]McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM: REporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat 2006, 100(2):229-235.
• [45]Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP: Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 1998, 4(7):844-847.
• [46]Skacel M, Skilton B, Pettay JD, Tubbs RR: Tissue microarrays: a powerful tool for high-throughput analysis of clinical specimens: a review of the method with validation data. Appl Immunohistochem Mol Morphol 2002, 10(1):1-6.
• [47]Fountzilas G, Kourea HP, Bobos M, Televantou D, Kotoula V, Papadimitriou C, Papazisis KT, Timotheadou E, Efstratiou I, Koutras A: Paclitaxel and bevacizumab as first line combined treatment in patients with metastatic breast cancer: the Hellenic Cooperative Oncology Group experience with biological marker evaluation. Anticancer Res 2011, 31(9):3007-3018.
• [48]Christodoulou C, Kostopoulos I, Kalofonos HP, Lianos E, Bobos M, Briasoulis E, Gogas H, Razis E, Skarlos DV, Fountzilas G: Trastuzumab combined with pegylated liposomal doxorubicin in patients with metastatic breast cancer. phase II Study of the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation. Oncology 2009, 76(4):275-285.
• [49]Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 2007, 25(1):118-145.
• [50]Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M: American society of clinical oncology/college of American pathologists guideline recommendations for immunohistochemical testing of Estrogen and progesterone receptors in breast cancer. J Clin Oncol 2010, 28(16):2784-2795.
• [51]Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, Watson M, Davies S, Bernard PS, Parker JS: Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 2009, 101(10):736-750.
• [52]Bhargava R, Lal P, Chen B: HER-2/neu and topoisomerase IIa gene amplification and protein expression in invasive breast carcinomas: chromogenic in situ hybridization and immunohistochemical analyses. Am J Clin Pathol 2005, 123(6):889-895.
• [53]Press MF, Sauter G, Buyse M, Bernstein L, Guzman R, Santiago A, Villalobos IE, Eiermann W, Pienkowski T, Martin M: Alteration of topoisomerase II-alpha gene in human breast cancer: association with responsiveness to anthracycline-based chemotherapy. J Clin Oncol 2011, 29(7):859-867.
• [54]Vanden Bempt I, Van Loo P, Drijkoningen M, Neven P, Smeets A, Christiaens MR, Paridaens R, De Wolf-Peeters C: Polysomy 17 in breast cancer: clinicopathologic significance and impact on HER-2 testing. J Clin Oncol 2008, 26(30):4869-4874.
• [55]Perez EA, Reinholz MM, Hillman DW, Tenner KS, Schroeder MJ, Davidson NE, Martino S, Sledge GW, Harris LN, Gralow JR: HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. J Clin Oncol 2010, 28(28):4307-4315.
• [56]Dafni U, Bobos M, Tsolaki E, Batistatou A, Koletsa F, Televantou D, Gogas H, Linardou H, Pectasides D, Kalogeras KT, Galani E, Koutras A, Papadimitriou CA, Fountzilas G: Effect of HER2/Topoisomerase II alpha (TOP2A) Gene Status or Protein Expression and Chromosome 17 (CEP17) Polysomy on the Outcome of Breast Cancer Patients Treated with Anthracycline-Containing Dose-Dense Sequential Adjuvant Chemotherapy with or without Paclitaxel. A pooled analysis of two Hellenic Cooperative Oncology Group (HeCOG) phase III trials. Cancer Res 2011, 71(24 Suppl):Abstract nr PD05–02.
• [57]Sauter G, Lee J, Bartlett JM, Slamon DJ, Press MF: Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol 2009, 27(8):1323-1333.
• [58]Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JA, Sparano JA, Hunsberger S, Enos RA, Gelber RD: Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol 2007, 25(15):2127-2132.
• [59]Clark GM, McGuire WL: Follow-up study of HER-2/neu amplification in primary breast cancer. Cancer Res 1991, 51(3):944-948.
• [60]Allred DC, Clark GM, Tandon AK, Molina R, Tormey DC, Osborne CK, Gilchrist KW, Mansour EG, Abeloff M, Eudey L: HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma. J Clin Oncol 1992, 10(4):599-605.
• [61]Bonnefoi HR: Anthracyclines, HER2, and TOP2A: the verdict. Lancet Oncol 2011, 12(12):1084-1085.
• [62]Di Leo A, Desmedt C, Bartlett JM, Piette F, Ejlertsen B, Pritchard KI, Larsimont D, Poole C, Isola J, Earl H: HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer: a meta-analysis of individual patient data. Lancet Oncol 2011, 12(12):1134-1142.
• [63]Hicks DG, Tubbs RR: Assessment of the HER2 status in breast cancer by fluorescence in situ hybridization: a technical review with interpretive guidelines. Hum Pathol 2005, 36(3):250-261.
• [64]Nielsen KV, Ejlertsen B, Moller S, Jensen MB, Balslev E, Muller S, Knoop A, Mouridsen HT: Lack of independent prognostic and predictive value of centromere 17 copy number changes in breast cancer patients with known HER2 and TOP2A status. Mol Oncol 2012, 6(1):88-97.
• [65]O’Malley FP, Chia S, Tu D, Shepherd LE, Levine MN, Bramwell VH, Andrulis IL, Pritchard KI: Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy. J Natl Cancer Inst 2009, 101(9):644-650.
• [66]Varga Z, Tubbs RR, Wang Z, Sun Y, Noske A, Kradolfer D, Bosshard G, Jochum W, Moch H, Ohlschlegel C: Co-amplification of the HER2 gene and chromosome 17 centromere: a potential diagnostic pitfall in HER2 testing in breast cancer. Breast Cancer Res Treat 2012, 132(3):925-935.
• [67]She X, Horvath JE, Jiang Z, Liu G, Furey TS, Christ L, Clark R, Graves T, Gulden CL, Alkan C: The structure and evolution of centromeric transition regions within the human genome. Nature 2004, 430(7002):857-864.
• [68]Baehner FL, Achacoso N, Maddala T, Shak S, Quesenberry CP Jr, Goldstein LC, Gown AM, Habel LA: Human epidermal growth factor receptor 2 assessment in a case–control study: comparison of fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction performed by central laboratories. J Clin Oncol 2010, 28(28):4300-4306.
• [69]Zaczek A, Markiewicz A, Supernat A, Bednarz-Knoll N, Brandt B, Seroczynska B, Skokowski J, Szade J, Czapiewski P, Biernat W: Prognostic Value of TOP2A Gene Amplification and Chromosome 17 Polysomy in Early Breast Cancer. Pathol Oncol Res 2012, 18(4):885-894.
• [70]Munro AF, Cameron DA, Bartlett JM: Targeting anthracyclines in early breast cancer: new candidate predictive biomarkers emerge. Oncogene 2010, 29(38):5231-5240.
• [71]Pritchard KI, Munro A, O’Malley FP, Tu D, Li X, Levine MN, Shepherd L, Chia S, Bartlett JM: Chromosome 17 centromere (CEP17) duplication as a predictor of anthracycline response: evidence from the NCIC Clinical Trials Group (NCIC CTG) MA.5 Trial. Breast Cancer Res Treat 2012, 131(2):541-551.
• [72]Kim A, Shin HC, Bae YK, Kim MK, Kang SH, Lee SJ, Lee EH: Multiplication of Chromosome 17 Centromere Is Associated with Prognosis in Patients with Invasive Breast Cancers Exhibiting Normal HER2 and TOP2A Status. J Breast Cancer 2012, 15(1):24-33.
• [73]Vanden Bempt I, Drijkoningen M, De Wolf-Peeters C: The complexity of genotypic alterations underlying HER2-positive breast cancer: an explanation for its clinical heterogeneity. Curr Opin Oncol 2007, 19(6):552-557.
• [74]Hayashi N, Nakamura S, Yagata H, Shimoda Y, Ota H, Hortobagyi GN, Cristofanilli M, Ueno NT: Chromosome 17 polysomy in circulating tumor cells in patients with metastatic breast cancer: a case series. Int J Clin Oncol 2011, 16(5):596-600.
• [75]Torrisi R, Rotmensz N, Bagnardi V, Viale G, Curto BD, Dell’orto P, Veronesi P, Luini A, D’Alessandro C, Cardillo A: HER2 status in early breast cancer: relevance of cell staining patterns, gene amplification and polysomy 17. Eur J Cancer 2007, 43(16):2339-2344.
• [76]Krishnamurti U, Hammers JL, Atem FD, Storto PD, Silverman JF: Poor prognostic significance of unamplified chromosome 17 polysomy in invasive breast carcinoma. Mod Pathol 2009, 22(8):1044-1048.
• [77]Watters AD, Going JJ, Cooke TG, Bartlett JM: Chromosome 17 aneusomy is associated with poor prognostic factors in invasive breast carcinoma. Breast Cancer Res Treat 2003, 77(2):109-114.
• [78]Bose S, Mohammed M, Shintaku P, Rao PN: Her-2/neu gene amplification in low to moderately expressing breast cancers: possible role of chromosome 17/Her-2/neu polysomy. Breast J 2001, 7(5):337-344.
• [79]Ross JS: Human epidermal growth factor receptor 2 testing in 2010: does chromosome 17 centromere copy number make any difference? J Clin Oncol 2010, 28(28):4293-4295.