Genetic heterogeneity in breast cancer: the road to personalized medicine?

BMC Medicine

Carlos Caldas¹  Richard D Baird² 

[1] Cancer Research UK Cambridge Research Institute, Li KaShing Centre, Robinson Way, Cambridge CB2 0RE, UK;Department of Oncology, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Box 97, Cambridge CB4 3EJ, UK

关键词: Heterogeneity;    Personalized medicine;    Molecular profiling;    Whole-genome sequencing;    Next-generation sequencing;    Breast cancer;   

Others  :  856979
DOI  :  10.1186/1741-7015-11-151

 received in 2012-12-21, accepted in 2013-05-29,  发布年份 2013

【 摘 要 】

More women die from breast cancer across the world today than from any other type of malignancy. The clinical course of breast cancer varies tremendously between patients. While some of this variability is explained by traditional clinico-pathological factors (including patient age, tumor stage, histological grade and estrogen receptor status), molecular profiling studies have defined breast cancer subtypes with distinct clinical outcomes. This mini-review considers recent studies which have used genomics technologies in an attempt to identify new biomarkers of prognosis and treatment response. These studies highlight the genetic heterogeneity that exists within breast cancers in space and time.

【 授权许可】

   
2013 Baird and Caldas; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001, 98:10869-10874.
• [2]Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, Lapuk A, Neve RM, Qian Z, Ryder T, Chen F, Feiler H, Tokuyasu T, Kingsley C, Dairkee S, Meng Z, Chew K, Pinkel D, Jain A, Ljung BM, Esserman L, Albertson DG, Waldman FM, Gray JW: Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 2006, 10:529-541.
• [3]Gatza ML, Lucas JE, Barry WT, Kim JW, Wang Q, Crawford MD, Datto MB, Kelley M, Mathey-Prevot B, Potti A, Nevins JR: A pathway-based classification of human breast cancer. Proc Natl Acad Sci U S A 2010, 107:6994-6999.
• [4]Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN: The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 2009, 14:320-368.
• [5]Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW, Harris CC, McLellan MD, Fulton RS, Fulton LL, Abbott RM, Hoog J, Dooling DJ, Koboldt DC, Schmidt H, Kalicki J, Zhang Q, Chen L, Lin L, Wendl MC, McMichael JF, Magrini VJ, Cook L, McGrath SD, Vickery TL, Appelbaum E, Deschryver K, Davies S, Guintoli T, Lin L, et al.: Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 2010, 464:999-1005.
• [6]Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet J-P, Ahmann GJ, Adli M, Anderson KC, Ardlie KG, Auclair D, Baker A, Bergsagel PL, Bernstein BE, Drier Y, Fonseca R, Gabriel SB, Hofmeister CC, Jagannath S, Jakubowiak AJ, Krishnan A, Levy J, Liefeld T, Lonial S, Mahan S, Mfuko B, Monti S, Perkins LM, et al.: Initial genome sequencing and analysis of multiple myeloma. Nature 2011, 471:467-472.
• [7]Pleasance ED, Cheetham RK, Stephens PJ, McBride DJ, Humphray SJ, Greenman CD, Varela I, Lin M-L, Ordóñez GR, Bignell GR, Ye K, Alipaz J, Bauer MJ, Beare D, Butler A, Carter RJ, Chen L, Cox AJ, Edkins S, Kokko-Gonzales PI, Gormley NA, Grocock RJ, Haudenschild CD, Hims MM, James T, Jia M, Kingsbury Z, Leroy C, Marshall J, Menzies A, et al.: A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 2010, 463:191-196.
• [8]Stratton MR: Exploring the genomes of cancer cells: progress and promise. Science 2011, 331:1553-1558.
• [9]Nowell PC: The clonal evolution of tumor cell populations. Science 1976, 194:23-28.
• [10]Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012, 366:883-892.
• [11]Shah SP, Morin RD, Khattra J, Prentice L, Pugh T, Burleigh A, Delaney A, Gelmon K, Guliany R, Senz J, Steidl C, Holt RA, Jones S, Sun M, Leung G, Moore R, Severson T, Taylor GA, Teschendorff AE, Tse K, Turashvili G, Varhol R, Warren RL, Watson P, Zhao Y, Caldas C, Huntsman D, Hirst M, Marra MA, Aparicio S: Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature 2009, 461:809-813.
• [12]Nik-Zainal S, Van Loo P, Wedge DC, Alexandrov LB, Greenman CD, Lau KW, Raine K, Jones D, Marshall J, Ramakrishna M, Shlien A, Cooke SL, Hinton J, Menzies A, Stebbings LA, Leroy C, Jia M, Rance R, Mudie LJ, Gamble SJ, Stephens PJ, McLaren S, Tarpey PS, Papaemmanuil E, Davies HR, Varela I, McBride DJ, Bignell GR, Leung K, Butler AP, et al.: The life history of 21 breast cancers. Cell 2012, 149:994-1007.
• [13]Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P, Greenman CD, Raine K, Jones D, Hinton J, Marshall J, Stebbings LA, Menzies A, Martin S, Leung K, Chen L, Leroy C, Ramakrishna M, Rance R, Lau KW, Mudie LJ, Varela I, McBride DJ, Bignell GR, Cooke SL, Shlien A, Gamble J, Whitmore I, Maddison M, Tarpey PS, Davies HR, Papaemmanuil E, et al.: Mutational processes molding the genomes of 21 breast cancers. Cell 2012, 149:979-993.
• [14]Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, Turashvili G, Ding J, Tse K, Haffari G, Bashashati A, Prentice LM, Khattra J, Burleigh A, Yap D, Bernard V, McPherson A, Shumansky K, Crisan A, Giuliany R, Heravi-Moussavi A, Rosner J, Lai D, Birol I, Varhol R, Tam A, Dhalla N, Zeng T, Ma K, Chan SK, et al.: The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature 2012, 486:395-399.
• [15]Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, Nik-Zainal S, Martin S, Varela I, Bignell GR, Yates LR, Papaemmanuil E, Beare D, Butler A, Cheverton A, Gamble J, Hinton J, Jia M, Jayakumar A, Jones D, Latimer C, Lau KW, McLaren S, McBride DJ, Menzies A, Mudie L, Raine K, Rad R, Chapman MS, Teague J, et al.: The landscape of cancer genes and mutational processes in breast cancer. Nature 2012, 486:400-404.
• [16]Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM, Lawrence MS, Sivachenko AY, Sougnez C, Zou L, Cortes ML, Fernandez-Lopez JC, Peng S, Ardlie KG, Auclair D, Bautista-Piña V, Duke F, Francis J, Jung J, Maffuz-Aziz A, Onofrio RC, Parkin M, Pho NH, Quintanar-Jurado V, Ramos AH, Rebollar-Vega R, Rodriguez-Cuevas S, Romero-Cordoba SL, Schumacher SE, Stransky N, et al.: Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 2012, 486:405-409.
• [17]Curtis C, Shah SP, Chin S-F, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Gräf S, Ha G, Haffari G, Bashashati A, Russell R, McKinney S, Langerød A, Green A, Provenzano E, Wishart G, Pinder S, Watson P, Markowetz F, Murphy L, Ellis IO, Purushotham A, Børresen-Dale A-L, Brenton JD, Tavaré S, Caldas C, METABRIC group, et al.: The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2012, 486:346-352.
• [18]Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA: Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011, 121:2750-2767.
• [19]Leth-Larsen R, Terp MG, Christensen AG, Elias D, Kühlwein T, Jensen ON, Petersen OW, Ditzel HJ: Functional heterogeneity within the CD44 high human breast cancer stem cell-like compartment reveals a gene signature predictive of distant metastasis. MolMed 2012, 18:1109-1121.
• [20]Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, Van Tine BA, Hoog J, Goiffon RJ, Goldstein TC, Ng S, Lin L, Crowder R, Snider J, Ballman K, Weber J, Chen K, Koboldt DC, Kandoth C, Schierding W, McMichael JF, Miller CA, Lu C, Harris CC, McLellan MD, Wendl MC, DeSchryver K, Allred DC, Esserman L, Unzeitig G, et al.: Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature 2012, 486:353-360.
• [21]Cancer Genome Atlas N, Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, Fulton LL, Dooling DJ, Ding L, Mardis ER, Wilson RK, Ally A, Balasundaram M, Butterfield YSN, Carlsen R, Carter C, Chu A, Chuah E, Chun H-JE, Coope RJN, Dhalla N, Guin R, Hirst C, Hirst M, Holt RA, Lee D, Li HI, Mayo M, Moore RA, Mungall AJ, et al.: Comprehensive molecular portraits of human breast tumours. Nature 2012, 490:61-70.
• [22]Meyerson M, Gabriel S, Getz G: Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet 2010, 11:685-696.
• [23]Aurilio G, Disalvatore D, Bagnardi V, Munzone E, Adamoli L, Curigliano G, Pruneri G, Sciandivasci A, De Vita F, Goldhirsch A, Nole F: A meta-analysis of receptor status discordance between primary breast cancer and metastases. 2012 ASCO Annual Meeting. J Clin Oncol 2012, 30:Abstract No 546.
• [24]Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DW, Kaper F, Dawson S-J, Piskorz AM, Jimenez-Linan M, Bentley D, Hadfield J, May AP, Caldas C, Brenton JD, Rosenfeld N: Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. SciTransl Med 2012, 4:136ra68.
• [25]Dawson S-J, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin S-F, Dunning MJ, Gale D, Forshew T, Mahler-Araujo B, Rajan S, Humphray S, Becq J, Halsall D, Wallis M, Bentley D, Caldas C, Rosenfeld N: Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 2013, 368:1199-1209.
• [26]Murtaza M, Dawson S-J, Tsui DW, Gale D, Forshew T, Piskorz AM, Parkinson C, Chin S-F, Kingsbury Z, Wong ASC, Marass F, Humphray S, Hadfield J, Bentley D, Chin TM, Brenton JD, Caldas C, Rosenfeld N: Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013, 497:108-112.
• [27]Farquhar C, Marjoribanks J, Basser R, Hetrick S, Lethaby A: High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer. Cochrane Database Syst Rev 2005. CD003142
• [28]Gatenby RA: A change of strategy in the war on cancer. Nature 2009, 459:508-509.
• [29]Baird RD, Kaye SB: Drug resistance reversal-are we getting closer? Eur J Cancer 2003, 39:2450-2461.
• [30]Yap TA, Sandhu SK, Workman P, De Bono JS: Envisioning the future of early anticancer drug development. Nat Rev Cancer 2010, 10:514-523.