title: A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast.
abstract: BACKGROUND
  For women with ductal carcinoma in situ (DCIS) of the breast, the risk of developing an ipsilateral breast event (IBE; defined as local recurrence of DCIS or invasive carcinoma) after surgical excision without radiation is not well defined by clinical and pathologic characteristics.
  
  
  METHODS
  The Oncotype DX breast cancer assay was performed for patients with DCIS treated with surgical excision without radiation in the Eastern Cooperative Oncology Group (ECOG) E5194 study. The association of the prospectively defined DCIS Score (calculated from seven cancer-related genes and five reference genes) with the risk of developing an IBE was analyzed using Cox regression. All statistical tests were two-sided.
  
  
  RESULTS
  There were 327 patients with adequate tissue for analysis. The continuous DCIS Score was statistically significantly associated with the risk of developing an IBE (hazard ratio [HR] = 2.31, 95% confidence interval [CI] = 1.15 to 4.49; P = .02) when adjusted for tamoxifen use (prespecified primary analysis) and with invasive IBE (unadjusted HR = 3.68, 95% CI = 1.34 to 9.62; P = .01). For the prespecified DCIS risk groups of low, intermediate, and high, the 10-year risks of developing an IBE were 10.6%, 26.7%, and 25.9%, respectively, and for an invasive IBE, 3.7%, 12.3%, and 19.2%, respectively (both log rank P ≤ .006). In multivariable analyses, factors associated with IBE risk were DCIS Score, tumor size, and menopausal status (all P ≤ .02).
  
  
  CONCLUSIONS
  The DCIS Score quantifies IBE risk and invasive IBE risk, complements traditional clinical and pathologic factors, and provides a new clinical tool to improve selecting individualized treatment for women with DCIS who meet the ECOG E5194 criteria.
authors: Department of Radiation Oncology, Albert Einstein Medical Center, Philadelphia, PA 19141, USA. solin@einstein.edu
authors: Lawrence J
authors: LJ
authors: Solin
authors: Robert
authors: R
authors: Gray
authors: Frederick L
authors: FL
authors: Baehner
authors: Steven M
authors: SM
authors: Butler
authors: Lorie L
authors: LL
authors: Hughes
authors: Carl
authors: C
authors: Yoshizawa
authors: Diana B
authors: DB
authors: Cherbavaz
authors: Steven
authors: S
authors: Shak
authors: David L
authors: DL
authors: Page
authors: George W
authors: GW
authors: Sledge
authors: Nancy E
authors: NE
authors: Davidson
authors: James N
authors: JN
authors: Ingle
authors: Edith A
authors: EA
authors: Perez
authors: William C
authors: WC
authors: Wood
authors: Joseph A
authors: JA
authors: Sparano
authors: Sunil
authors: S
authors: Badve
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D015412:Mastectomy, Segmental; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor
references: J Natl Cancer Inst. 2011 Mar 16;103(6):478-88
references: 21398619
references: J Clin Oncol. 2009 Nov 10;27(32):5319-24
references: 19826126
references: J Clin Oncol. 2012 Apr 20;30(12):1268-73
references: 22393101
references: J Natl Cancer Inst Monogr. 2010;2010(41):162-77
references: 20956824
references: J Clin Oncol. 2001 Apr 15;19(8):2263-71
references: 11304780
references: Clin Chem. 2007 Jun;53(6):1084-91
references: 17463177
references: Br J Cancer. 2007 Sep 17;97(6):725-9
references: 17848911
references: Breast J. 2012 Jan-Feb;18(1):8-15
references: 22107336
references: J Clin Oncol. 2006 Mar 1;24(7):1031-6
references: 16461781
references: Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1397-403
references: 16750316
references: J Clin Oncol. 1998 Feb;16(2):441-52
references: 9469327
references: N Engl J Med. 1999 May 13;340(19):1455-61
references: 10320383
references: J Clin Oncol. 2008 Mar 10;26(8):1247-52
references: 18250350
references: J Natl Cancer Inst Monogr. 2010;2010(41):130-3
references: 20956816
references: N Engl J Med. 2004 Dec 30;351(27):2817-26
references: 15591335
references: Arch Pathol Lab Med. 2009 Jan;133(1):15-25
references: 19123730
references: Cancer. 2000 Feb 15;88(4):946-54
references: 10679665
references: Cancer. 1999 Aug 1;86(3):429-38
references: 10430251
references: Lancet. 1999 Jun 12;353(9169):1993-2000
references: 10376613
references: Breast Cancer Res. 2006;8(3):R25
references: 16737553
references: N Engl J Med. 2004 Apr 1;350(14):1430-41
references: 15070793
references: J Clin Oncol. 2010 Apr 1;28(10):1677-83
references: 20065188
references: J Natl Cancer Inst. 2009 Nov 4;101(21):1446-52
references: 19815849
references: J Natl Cancer Inst. 2010 Feb 3;102(3):161-9
references: 20071686
references: J Clin Pathol. 2010 Jun;63(6):513-7
references: 20498025
references: Breast J. 2001 Sep-Oct;7(5):292-302
references: 11906438
references: Br J Cancer. 2012 Mar 13;106(6):1160-5
references: 22361634
references: Lancet Oncol. 2011 Jan;12(1):21-9
references: 21145284
references: Semin Oncol. 2001 Aug;28(4):400-18
references: 11498833
references: J Natl Cancer Inst. 2004 Mar 17;96(6):443-8
references: 15026469
references: J Clin Oncol. 2011 Nov 1;29(31):4160-7
references: 21947828
references: Am J Pathol. 2004 Jan;164(1):35-42
references: 14695316
references: J Natl Cancer Inst. 2010 May 5;102(9):627-37
references: 20427430
references: Hum Pathol. 1998 Sep;29(9):915-23
references: 9744307
references: J Natl Cancer Inst Monogr. 2010;2010(41):187-92
references: 20956827
references: J Clin Oncol. 2006 Jul 20;24(21):3381-7
references: 16801628
references: Breast Cancer Res Treat. 2011 May;127(1):251-7
references: 20931276
references: J Natl Cancer Inst Monogr. 2010;2010(41):193-6
references: 20956828