Biology of DCIS and Progression to Invasive Disease

  • Sanaz A. Jansen
Part of the Medical Radiology book series (MEDRAD)


Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer in which neoplastic cells are confined within the breast milk duct basement membrane. Prior to the widespread use of screening mammography DCIS was a rare diagnosis, but now comprises 20–30 % of all newly diagnosed breast cancers in the US. This diagnosis is often treated in a fashion similar to invasive breast cancer. Standard treatment typically consists of breast-conserving surgery (with or without radiotherapy) or mastectomy. There is a growing clinical concern that many patients with DCIS are being over-treated since their disease will never progress to invasive life-threatening carcinomas. But how can this indolent subset be identified? A better understanding of the biology of DCIS and how it transforms into invasive cancer will shed light on this important clinical goal. In this chapter, we identify important molecular pathways responsible for regulating cellular proliferation, apoptosis, and genome integrity that are altered in DCIS. We find surprisingly few differences on a genomic or gene-expression level between DCIS and invasive disease. We introduce diverse models of DCIS progression that are stochastic versus predetermined and discuss how the empirical data supports or challenges these models. Due to the considerable difficulty of studying DCIS, many unanswered questions remain. Improvements in molecular assays and model systems may provide further insights into the etiology and natural history of this disease entity.


Invasive Ductal Carcinoma Intratumor Heterogeneity Comedo Necrosis Genetically Engineer Mouse Preinvasive Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Ductal carcinoma in situ


Deoxyribonucleic acid


Estrogen receptor


Fluorescence in situ hybridization


Genetically engineered mice


Human epidermal growth factor receptor 2


Invasive ductal carcinoma




Mammary intraepithelial neoplasia


Magnetic resonance imaging


Progesterone receptor


Ribonucleic acid


Terminal ductal lobular unit



I would like to thank Dr. Amit Adhikari and the NIH Fellows Editorial Board for useful feedback.


  1. Allegra CJ, Aberle DR, Ganschow P, Hahn SM, Lee CN, Millon-Underwood S, Pike MC, Reed SD, Saftlas AF, Scarvalone SA, Schwartz AM, Slomski C, Yothers G, Zon R (2010) National Institutes of Health state-of-the-science conference statement: diagnosis and management of ductal carcinoma in situ september 22–24, 2009. J Natl Cancer Inst 102:161–169CrossRefPubMedGoogle Scholar
  2. Allinen M, Beroukhim R, Cai L, Brennan C, Lahti-Domenici J, Huang H, Porter D, Hu M, Chin L, Richardson A, Schnitt S, Sellers WR, Polyak K (2004) Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell 6:17–32CrossRefPubMedGoogle Scholar
  3. Allred DC (2010) Ductal carcinoma in situ: terminology, classification, and natural history. J Natl Cancer Inst Monogr 2010:134–138CrossRefPubMedGoogle Scholar
  4. Allred DC, Wu Y, Mao S, Nagtegaal ID, Lee S, Perou CM, Mohsin SK, O’Connell P, Tsimelzon A, Medina D (2008) Ductal carcinoma in situ and the emergence of diversity during breast cancer evolution. Clin Cancer Res 14:370–378CrossRefPubMedGoogle Scholar
  5. Altintas S, Lambein K, Huizing MT, Braems G, Asjoe FT, Hellemans H, Van Marck E, Weyler J, Praet M, Van den Broecke R, Vermorken JB, Tjalma WA (2009) Prognostic significance of oncogenic markers in ductal carcinoma in situ of the breast: a clinicopathologic study. Breast J 15:120–132CrossRefPubMedGoogle Scholar
  6. Arun B, Vogel KJ, Lopez A, Hernandez M, Atchley D, Broglio KR, Amos CI, Meric-Bernstam F, Kuerer H, Hortobagyi GN, Albarracin CT (2009) High prevalence of preinvasive lesions adjacent to BRCA1/2-associated breast cancers. Cancer Prev Res (Phila) 2:122–127CrossRefGoogle Scholar
  7. Behbod F, Kittrell FS, LaMarca H, Edwards D, Kerbawy S, Heestand JC, Young E, Mukhopadhyay P, Yeh HW, Allred DC, Hu M, Polyak K, Rosen JM, Medina D (2009) An intraductal human-in-mouse transplantation model mimics the subtypes of ductal carcinoma in situ. Breast Cancer Res 11:R66CrossRefPubMedPubMedCentralGoogle Scholar
  8. Bijker N, van Tienhoven G (2010) Local and systemic outcomes in DCIS based on tumor and patient characteristics: the radiation oncologist’s perspective. J Natl Cancer Inst Monogr 2010:178–180CrossRefPubMedGoogle Scholar
  9. Boland GP, Butt IS, Prasad R, Knox WF, Bundred NJ (2004) COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ. Br J Cancer 90:423–429CrossRefPubMedPubMedCentralGoogle Scholar
  10. Bombonati A, Sgroi DC (2011) The molecular pathology of breast cancer progression. J Pathol 223:307–317CrossRefPubMedPubMedCentralGoogle Scholar
  11. Bose S, Chandran S, Mirocha JM, Bose N (2006) The Akt pathway in human breast cancer: a tissue-array-based analysis. Mod Pathol 19:238–245CrossRefPubMedGoogle Scholar
  12. Buerger H, Otterbach F, Simon R, Poremba C, Diallo R, Decker T, Riethdorf L, Brinkschmidt C, Dockhorn-Dworniczak B, Boecker W (1999a) Comparative genomic hybridization of ductal carcinoma in situ of the breast-evidence of multiple genetic pathways. J Pathol 187:396–402CrossRefPubMedGoogle Scholar
  13. Buerger H, Otterbach F, Simon R, Schafer KL, Poremba C, Diallo R, Brinkschmidt C, Dockhorn-Dworniczak B, Boecker W (1999b) Different genetic pathways in the evolution of invasive breast cancer are associated with distinct morphological subtypes. J Pathol 189:521–526CrossRefPubMedGoogle Scholar
  14. Cardiff RD, Borowsky AD (2010) Precancer: sequentially acquired or predetermined? Toxicol Pathol 38:171–179CrossRefPubMedGoogle Scholar
  15. Cardiff RD, Anver MR, Gusterson BA, Hennighausen L, Jensen RA, Merino MJ, Rehm S, Russo J, Tavassoli FA, Wakefield LM, Ward JM, Green JE (2000) The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting. Oncogene 19:968–988CrossRefPubMedGoogle Scholar
  16. Chin K, de Solorzano CO, Knowles D, Jones A, Chou W, Rodriguez EG, Kuo WL, Ljung BM, Chew K, Myambo K, Miranda M, Krig S, Garbe J, Stampfer M, Yaswen P, Gray JW, Lockett SJ (2004) In situ analyses of genome instability in breast cancer. Nat Genet 36:984–988CrossRefPubMedGoogle Scholar
  17. Clark SE, Warwick J, Carpenter R, Bowen RL, Duffy SW, Jones JL (2011) Molecular subtyping of DCIS: heterogeneity of breast cancer reflected in pre-invasive disease. Br J Cancer 104:120–127CrossRefPubMedPubMedCentralGoogle Scholar
  18. Claus EB, Petruzella S, Matloff E, Carter D (2005) Prevalence of BRCA1 and BRCA2 mutations in women diagnosed with ductal carcinoma in situ. JAMA 293:964–969CrossRefPubMedGoogle Scholar
  19. Correa C, McGale P, Taylor C, Wang Y, Clarke M, Davies C, Peto R, Bijker N, Solin L, Darby S (2010) Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast. J Natl Cancer Inst Monogr 2010:162–177CrossRefPubMedGoogle Scholar
  20. Damonte P, Hodgson JG, Chen JQ, Young LJ, Cardiff RD, Borowsky AD (2008) Mammary carcinoma behavior is programmed in the precancer stem cell. Breast Cancer Res: BCR 10:R50CrossRefPubMedPubMedCentralGoogle Scholar
  21. D’Orsi CJ (2010) Imaging for the diagnosis and management of ductal carcinoma in situ. J Natl Cancer Inst Monogr 2010:214–217CrossRefPubMedGoogle Scholar
  22. Eng-Wong J, Costantino JP, Swain SM (2010) The impact of systemic therapy following ductal carcinoma in situ. J Natl Cancer Inst Monogr 2010:200–203CrossRefPubMedGoogle Scholar
  23. Erbas B, Provenzano E, Armes J, Gertig D (2006) The natural history of ductal carcinoma in situ of the breast: a review. Breast Cancer Res Treat 97:135–144CrossRefPubMedGoogle Scholar
  24. Espina V, Liotta LA (2011) What is the malignant nature of human ductal carcinoma in situ? Nat Rev Cancer 11:68–75CrossRefPubMedPubMedCentralGoogle Scholar
  25. Frech MS, Halama ED, Tilli MT, Singh B, Gunther EJ, Chodosh LA, Flaws JA, Furth PA (2005) Deregulated estrogen receptor alpha expression in mammary epithelial cells of transgenic mice results in the development of ductal carcinoma in situ. Cancer Res 65:681–685PubMedGoogle Scholar
  26. Gauthier ML, Berman HK, Miller C, Kozakeiwicz K, Chew K, Moore D, Rabban J, Chen YY, Kerlikowske K, Tlsty TD (2007) Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors. Cancer Cell 12:479–491CrossRefPubMedPubMedCentralGoogle Scholar
  27. Glover JA, Hughes CM, Cantwell MM, Murray LJ (2011) A systematic review to establish the frequency of cyclooxygenase-2 expression in normal breast epithelium, ductal carcinoma in situ, microinvasive carcinoma of the breast and invasive breast cancer. Br J Cancer 105:13–17CrossRefPubMedPubMedCentralGoogle Scholar
  28. Green JE, Shibata MA, Yoshidome K, Liu ML, Jorcyk C, Anver MR, Wigginton J, Wiltrout R, Shibata E, Kaczmarczyk S, Wang W, Liu ZY, Calvo A, Couldrey C (2000) The C3(1)/SV40 T-antigen transgenic mouse model of mammary cancer: ductal epithelial cell targeting with multistage progression to carcinoma. Oncogene 19:1020–1027CrossRefPubMedGoogle Scholar
  29. Guidi AJ, Fischer L, Harris JR, Schnitt SJ (1994) Microvessel density and distribution in ductal carcinoma in situ of the breast. J Natl Cancer Inst 86:614–619CrossRefPubMedGoogle Scholar
  30. Hernandez L, Wilkerson PM, Lambros MB, Campion-Flora A, Rodrigues DN, Gauthier A, Cabral C, Pawar V, Mackay A, A’Hern R, Marchio C, Palacios J, Natrajan R, Weigelt B, Reis-Filho JS (2012) Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection. J Pathol 227(1):42–52CrossRefPubMedGoogle Scholar
  31. Hieken TJ, Farolan M, D’Alessandro S, Velasco JM (2001) Predicting the biologic behavior of ductal carcinoma in situ: an analysis of molecular markers. Surgery 130:593–600 discussion 600–591CrossRefPubMedGoogle Scholar
  32. Hu M, Yao J, Cai L, Bachman KE, van den Brule F, Velculescu V, Polyak K (2005) Distinct epigenetic changes in the stromal cells of breast cancers. Nat Genet 37:899–905CrossRefPubMedGoogle Scholar
  33. Hu M, Yao J, Carroll DK, Weremowicz S, Chen H, Carrasco D, Richardson A, Violette S, Nikolskaya T, Nikolsky Y, Bauerlein EL, Hahn WC, Gelman RS, Allred C, Bissell MJ, Schnitt S, Polyak K (2008) Regulation of in situ to invasive breast carcinoma transition. Cancer Cell 13:394–406CrossRefPubMedPubMedCentralGoogle Scholar
  34. Hu M, Peluffo G, Chen H, Gelman R, Schnitt S, Polyak K (2009) Role of COX-2 in epithelial-stromal cell interactions and progression of ductal carcinoma in situ of the breast. Proc Natl Acad Sci U S A 106:3372–3377CrossRefPubMedPubMedCentralGoogle Scholar
  35. Hwang ES (2010) The impact of surgery on ductal carcinoma in situ outcomes: the use of mastectomy. J Natl Cancer Inst Monogr 2010:197–199CrossRefPubMedGoogle Scholar
  36. Hwang ES, DeVries S, Chew KL, Moore DH 2nd, Kerlikowske K, Thor A, Ljung BM, Waldman FM (2004) Patterns of chromosomal alterations in breast ductal carcinoma in situ. Clin Cancer Res 10:5160–5167CrossRefPubMedGoogle Scholar
  37. Hwang ES, McLennan JL, Moore DH, Crawford BB, Esserman LJ, Ziegler JL (2007) Ductal carcinoma in situ in BRCA mutation carriers. J Clin Oncol (Official Journal of the American Society of Clinical Oncology) 25:642–647CrossRefGoogle Scholar
  38. Jansen SA (2011) Ductal carcinoma in situ: detection, diagnosis, and characterization with magnetic resonance imaging. Semin Ultrasound CT MR 32:306–318CrossRefPubMedGoogle Scholar
  39. Jansen SA, Newstead GM, Abe H, Shimauchi A, Schmidt RA, Karczmar GS (2007) Pure ductal carcinoma in situ: kinetic and morphologic MR characteristics compared with mammographic appearance and nuclear grade. Radiology 245:684–691CrossRefPubMedGoogle Scholar
  40. Jansen SA, Conzen SD, Fan X, Markiewicz EJ, Newstead GM, Karczmar GS (2009) Magnetic resonance imaging of the natural history of in situ mammary neoplasia in transgenic mice: a pilot study. Breast Cancer Res 11:R65CrossRefPubMedPubMedCentralGoogle Scholar
  41. Johnson CE, Gorringe KL, Thompson ER, Opeskin K, Boyle SE, Wang Y, Hill P, Mann GB, Campbell IG (2011) Identification of copy number alterations associated with the progression of DCIS to invasive ductal carcinoma. Breast Cancer Res Treat Google Scholar
  42. Kane RL, Virnig BA, Shamliyan T, Wang SY, Tuttle TM, Wilt TJ (2010) The impact of surgery, radiation, and systemic treatment on outcomes in patients with ductal carcinoma in situ. J Natl Cancer Inst Monogr 2010:130–133CrossRefPubMedGoogle Scholar
  43. Kerlikowske K (2010) Epidemiology of ductal carcinoma in situ. J Natl Cancer Inst Monogr 2010:139–141CrossRefPubMedGoogle Scholar
  44. Kerlikowske K, Molinaro AM, Gauthier ML, Berman HK, Waldman F, Bennington J, Sanchez H, Jimenez C, Stewart K, Chew K, Ljung BM, Tlsty TD (2010) Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis. J Natl Cancer Inst 102:627–637CrossRefPubMedPubMedCentralGoogle Scholar
  45. King TA, Sakr RA, Muhsen S, Andrade VP, Giri D, Van Zee KJ, Morrow M (2011) Is there a low-grade precursor pathway in breast cancer? Ann Surg Oncol 19:1115–1121CrossRefPubMedGoogle Scholar
  46. Knudsen ES, Ertel A, Davicioni E, Kline J, Schwartz GF, Witkiewicz AK (2011) Progression of ductal carcinoma in situ to invasive breast cancer is associated with gene expression programs of EMT and myoepithelia. Breast Cancer Res TreatGoogle Scholar
  47. Kuerer HM, Albarracin CT, Yang WT, Cardiff RD, Brewster AM, Symmans WF, Hylton NM, Middleton LP, Krishnamurthy S, Perkins GH, Babiera G, Edgerton ME, Czerniecki BJ, Arun BK, Hortobagyi GN (2009) Ductal carcinoma in situ: state of the science and roadmap to advance the field. J Clin Oncol (Official Journal of the American Society of Clinical Oncology) 27:279–288CrossRefGoogle Scholar
  48. Kuhl CK, Schrading S, Bieling HB, Wardelmann E, Leutner CC, Koenig R, Kuhn W, Schild HH (2007) MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study. Lancet 370:485–492CrossRefPubMedGoogle Scholar
  49. Kulkarni S, Patil DB, Diaz LK, Wiley EL, Morrow M, Khan SA (2008) COX-2 and PPARgamma expression are potential markers of recurrence risk in mammary duct carcinoma in situ. BMC Cancer 8:36CrossRefPubMedPubMedCentralGoogle Scholar
  50. Lari SA, Kuerer HM (2011) Biological markers in DCIS and risk of breast recurrence: a systematic review. J Cancer 2:232–261CrossRefPubMedPubMedCentralGoogle Scholar
  51. Lehman CD (2010) Magnetic resonance imaging in the evaluation of ductal carcinoma in situ. J Natl Cancer Inst Monogr 2010:150–151CrossRefPubMedGoogle Scholar
  52. Li Y, Zhang Y, Hill J, Kim HT, Shen Q, Bissonnette RP, Lamph WW, Brown PH (2008) The rexinoid, bexarotene, prevents the development of premalignant lesions in MMTV-erbB2 mice. Br J Cancer 98:1380–1388CrossRefPubMedPubMedCentralGoogle Scholar
  53. Livasy CA, Perou CM, Karaca G, Cowan DW, Maia D, Jackson S, Tse CK, Nyante S, Millikan RC (2007) Identification of a basal-like subtype of breast ductal carcinoma in situ. Human Pathol 38:197–204CrossRefGoogle Scholar
  54. Ma XJ, Salunga R, Tuggle JT, Gaudet J, Enright E, McQuary P, Payette T, Pistone M, Stecker K, Zhang BM, Zhou YX, Varnholt H, Smith B, Gadd M, Chatfield E, Kessler J, Baer TM, Erlander MG, Sgroi DC (2003) Gene expression profiles of human breast cancer progression. Proc Natl Acad Sci U S A 100:5974–5979CrossRefPubMedPubMedCentralGoogle Scholar
  55. Ma XJ, Dahiya S, Richardson E, Erlander M, Sgroi DC (2009) Gene expression profiling of the tumor microenvironment during breast cancer progression. Breast Cancer Res: BCR 11:R7CrossRefPubMedPubMedCentralGoogle Scholar
  56. Maglione JE, Moghanaki D, Young LJ, Manner CK, Ellies LG, Joseph SO, Nicholson B, Cardiff RD, MacLeod CL (2001) Transgenic polyoma middle-T mice model premalignant mammary disease. Cancer Res 61:8298–8305PubMedGoogle Scholar
  57. Maglione JE, McGoldrick ET, Young LJ, Namba R, Gregg JP, Liu L, Moghanaki D, Ellies LG, Borowsky AD, Cardiff RD, MacLeod CL (2004) Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths: single origin, divergent evolution, and multiple outcomes. Mol Cancer Ther 3:941–953PubMedGoogle Scholar
  58. Maley CC, Galipeau PC, Finley JC, Wongsurawat VJ, Li X, Sanchez CA, Paulson TG, Blount PL, Risques RA, Rabinovitch PS, Reid BJ (2006) Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat Genet 38:468–473CrossRefPubMedGoogle Scholar
  59. Maroulakou IG, Anver M, Garrett L, Green JE (1994) Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene. Proc Natl Acad Sci U S A 91:11236–11240CrossRefPubMedPubMedCentralGoogle Scholar
  60. Marusyk A, Polyak K (2010) Tumor heterogeneity: causes and consequences. Biochim Biophys Acta 1805:105–117PubMedPubMedCentralGoogle Scholar
  61. Medina D, Kittrell FS, Shepard A, Stephens LC, Jiang C, Lu J, Allred DC, McCarthy M, Ullrich RL (2002) Biological and genetic properties of the p53 null preneoplastic mammary epithelium. FASEB J 16:881–883PubMedGoogle Scholar
  62. Millar EK, Tran K, Marr P, Graham PH (2007) p27KIP-1, cyclin A and cyclin D1 protein expression in ductal carcinoma in situ of the breast: p27KIP-1 correlates with hormone receptor status but not with local recurrence. Pathol Int 57:183–189CrossRefPubMedGoogle Scholar
  63. Miller FR, Santner SJ, Tait L, Dawson PJ (2000) xenograft model of human comedo ductal carcinoma in situ. J Natl Cancer Inst 92:1185–1186CrossRefPubMedGoogle Scholar
  64. Namba R, Maglione JE, Young LJ, Borowsky AD, Cardiff RD, MacLeod CL, Gregg JP (2004) Molecular characterization of the transition to malignancy in a genetically engineered mouse-based model of ductal carcinoma in situ. Mol Cancer Res 2:453–463PubMedGoogle Scholar
  65. Namba R, Maglione JE, Davis RR, Baron CA, Liu S, Carmack CE, Young LJ, Borowsky AD, Cardiff RD, Gregg JP (2006) Heterogeneity of mammary lesions represent molecular differences. BMC Cancer 6:275CrossRefPubMedPubMedCentralGoogle Scholar
  66. Okumura Y, Yamamoto Y, Zhang Z, Toyama T, Kawasoe T, Ibusuki M, Honda Y, Iyama K, Yamashita H, Iwase H (2008) Identification of biomarkers in ductal carcinoma in situ of the breast with microinvasion. BMC Cancer 8:287CrossRefPubMedPubMedCentralGoogle Scholar
  67. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752CrossRefPubMedGoogle Scholar
  68. Polyak K (2007) Breast cancer: origins and evolution. J Clin Invest 117:3155–3163CrossRefPubMedPubMedCentralGoogle Scholar
  69. Polyak K (2010) Molecular markers for the diagnosis and management of ductal carcinoma in situ. J Natl Cancer Inst Monogr 2010:210–213CrossRefPubMedGoogle Scholar
  70. Porter DA, Krop IE, Nasser S, Sgroi D, Kaelin CM, Marks JR, Riggins G, Polyak K (2001) A SAGE (serial analysis of gene expression) view of breast tumor progression. Cancer Res 61:5697–5702PubMedGoogle Scholar
  71. Porter D, Lahti-Domenici J, Keshaviah A, Bae YK, Argani P, Marks J, Richardson A, Cooper A, Strausberg R, Riggins GJ, Schnitt S, Gabrielson E, Gelman R, Polyak K (2003) Molecular markers in ductal carcinoma in situ of the breast. Mol Cancer Res 1:362–375PubMedGoogle Scholar
  72. Rakovitch E, Nofech-Mozes S, Hanna W, Narod S, Thiruchelvam D, Saskin R, Spayne J, Taylor C, Paszat L (2012) HER2/neu and Ki-67 expression predict non-invasive recurrence following breast-conserving therapy for ductal carcinoma in situ. Br J Cancer 106:1160–1165CrossRefPubMedPubMedCentralGoogle Scholar
  73. Roylance R, Gorman P, Harris W, Liebmann R, Barnes D, Hanby A, Sheer D (1999) Comparative genomic hybridization of breast tumors stratified by histological grade reveals new insights into the biological progression of breast cancer. Cancer Res 59:1433–1436PubMedGoogle Scholar
  74. Sardanelli F, Podo F, Santoro F, Manoukian S, Bergonzi S, Trecate G, Vergnaghi D, Federico M, Cortesi L, Corcione S, Morassut S, Di Maggio C, Cilotti A, Martincich L, Calabrese M, Zuiani C, Preda L, Bonanni B, Carbonaro LA, Contegiacomo A, Panizza P, Di Cesare E, Savarese A, Crecco M, Turchetti D, Tonutti M, Belli P, Maschio AD (2010) Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the high breast cancer risk italian 1 study): final results. Invest Radiol 46:94–105CrossRefGoogle Scholar
  75. Schnitt SJ (2010) Local outcomes in ductal carcinoma in situ based on patient and tumor characteristics. J Natl Cancer Inst Monogr 2010:158–161CrossRefPubMedGoogle Scholar
  76. Schulze-Garg C, Lohler J, Gocht A, Deppert W (2000) A transgenic mouse model for the ductal carcinoma in situ (DCIS) of the mammary gland. Oncogene 19:1028–1037CrossRefPubMedGoogle Scholar
  77. Sgroi DC (2010) Preinvasive breast cancer. Ann Rev Pathol 5:193–221CrossRefGoogle Scholar
  78. Shamliyan T, Wang SY, Virnig BA, Tuttle TM, Kane RL (2010) Association between patient and tumor characteristics with clinical outcomes in women with ductal carcinoma in situ. J Natl Cancer Inst Monogr 2010:121–129CrossRefPubMedGoogle Scholar
  79. Smart CE, Simpson PT, Vargas AC, Lakhani SR (2011) Genetic alterations in normal and malignant breast tissue. In: Tot T (ed) Breast cancer: a lobar disease. Springer, LondonGoogle Scholar
  80. Smith KL, Adank M, Kauff N, Lafaro K, Boyd J, Lee JB, Hudis C, Offit K, Robson M (2007) BRCA mutations in women with ductal carcinoma in situ. Clin Cancer Res (Official Journal of the American Association for Cancer Research) 13:4306–4310CrossRefGoogle Scholar
  81. Solin LJ (2010) The impact of adding radiation treatment after breast conservation surgery for ductal carcinoma in situ of the breast. J Natl Cancer Inst Monogr 2010:187–192CrossRefPubMedGoogle Scholar
  82. Sontag L, Axelrod DE (2005) Evaluation of pathways for progression of heterogeneous breast tumors. J Theor Biol 232:179–189CrossRefPubMedGoogle Scholar
  83. Sorlie T (2011) How to personalise treatment in early breast cancer. Eur J Cancer 47(Suppl 3):S310–S311CrossRefPubMedGoogle Scholar
  84. Sorlie 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, Eystein Lonning P, Borresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874CrossRefPubMedPubMedCentralGoogle Scholar
  85. Tamimi RM, Baer HJ, Marotti J, Galan M, Galaburda L, Fu Y, Deitz AC, Connolly JL, Schnitt SJ, Colditz GA, Collins LC (2008) Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer. Breast Cancer Res 10:R67CrossRefPubMedPubMedCentralGoogle Scholar
  86. Tot T (2010) The origins of early breast carcinoma. Semin Diagn Pathol 27:62–68CrossRefPubMedGoogle Scholar
  87. Tot T (2011) Subgross morphology, the sick lobe hypothesis, and the success of breast conservation. Int J Breast Cancer 2011:634021CrossRefPubMedPubMedCentralGoogle Scholar
  88. Valdez KE, Fan F, Smith W, Allred DC, Medina D, Behbod F (2011) Human primary ductal carcinoma in situ (DCIS) subtype-specific pathology is preserved in a mouse intraductal (MIND) xenograft model. J Pathol 225:565–573CrossRefPubMedPubMedCentralGoogle Scholar
  89. Vincent-Salomon A, Lucchesi C, Gruel N, Raynal V, Pierron G, Goudefroye R, Reyal F, Radvanyi F, Salmon R, Thiery JP, Sastre-Garau X, Sigal-Zafrani B, Fourquet A, Delattre O (2008) Integrated genomic and transcriptomic analysis of ductal carcinoma in situ of the breast. Clin Cancer Res 14:1956–1965CrossRefPubMedGoogle Scholar
  90. Virnig BA, Wang SY, Shamilyan T, Kane RL, Tuttle TM (2010) Ductal carcinoma in situ: risk factors and impact of screening. J Natl Cancer Inst Monogr 2010:113–116CrossRefPubMedGoogle Scholar
  91. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532CrossRefPubMedGoogle Scholar
  92. Warner E, Causer PA, Wong JW, Wright FC, Jong RA, Hill KA, Messner SJ, Yaffe MJ, Narod SA, Plewes DB (2011) Improvement in DCIS detection rates by MRI over time in a high-risk breast screening study. Breast J 17:9–17CrossRefPubMedGoogle Scholar
  93. Wellings SR, Jensen HM, Marcum RG (1975) An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J Natl Cancer Inst 55:231–273PubMedGoogle Scholar
  94. Witkiewicz AK, Rivadeneira DB, Ertel A, Kline J, Hyslop T, Schwartz GF, Fortina P, Knudsen ES (2011) Association of RB/p16-pathway perturbations with DCIS recurrence: dependence on tumor versus tissue microenvironment. Am J Pathol 179:1171–1178CrossRefPubMedPubMedCentralGoogle Scholar
  95. Yu KD, Wu LM, Liu GY, Wu J, Di GH, Shen ZZ, Shao ZM (2011) Different distribution of breast cancer subtypes in breast ductal carcinoma in situ (DCIS), DCIS with microinvasion, and DCIS with invasion component. Ann Surg Oncol 18:1342–1348CrossRefPubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Mouse Cancer Genetics ProgramNational Cancer Institute, Frederick National Laboratory for Cancer ResearchFrederickUSA

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