title: Molecular phenotypes of DCIS predict overall and invasive recurrence.
abstract: BACKGROUND
  Molecular phenotypes of invasive breast cancer predict early recurrence. Ductal carcinoma in situ (DCIS) exhibits similar phenotypes, but their frequency and significance remain unclear. To determine whether DCIS molecular phenotypes predict recurrence, 314 women (median age 57.7 years) with primary DCIS who were screened or entered DCIS trials in a specialist breast unit from 1990 to 2010 were studied.
  
  
  METHODS
  Expression of Ki67, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) within primary DCIS was established using immunohistochemistry (IHC). Patients were subdivided into molecular phenotypes using IHC surrogates [Luminal A (ER/PR+HER2-), Luminal B (ER/PR+/HER2+), HER2 type (ER and PR-/HER2+) or triple negative (ER/PR/HER2)] and recurrence rates compared.
  
  
  RESULTS
  Overall, there were 57 (18.2%) recurrences, 35 (11.2%) DCIS and 22 (7%) invasive cancer. A low rate of recurrence at 5 years was seen in Luminal A DCIS (7.6%), compared with 15.8%-36.1% in other phenotypes. Independent predictors of overall recurrence on multivariate analysis were involved (<1 mm) surgical margins (HR 4.31, P < 0.001), high-grade lesions (HR 2.28, P < 0.024) and molecular phenotype (HR 5.14, P = 0.001 for Luminal B; HR 6.46, P < 0.001 for HER2 type and HR 3.27, P = 0.028 for triple-negative disease compared with Luminal A DCIS). Independent predictors for invasive recurrence were high Ki67 expression (HR 1.04, P = 0.021) and molecular phenotype (HR 13.4, P = 0.014 for Luminal B; HR 11.4, P = 0.027 for HER2 type and HR 10.3, P = 0.031 for triple negative compared with Luminal A DCIS).
  
  
  CONCLUSIONS
  DCIS molecular phenotype predicts for both overall and invasive recurrence. HER2 testing of DCIS could help clinicians individualise the treatment of patients with DCIS.
authors: Department of Academic Surgery, University Hospital of South Manchester, Manchester.
authors: K E
authors: KE
authors: Williams
authors: Department of Academic Surgery, University Hospital of South Manchester, Manchester.
authors: N L P
authors: NLP
authors: Barnes
authors: Department of Oncology Cytogenetics, The Christie NHS Foundation Trust, Manchester.
authors: A
authors: A
authors: Cramer
authors: Department of Academic Surgery, University Hospital of South Manchester, Manchester.
authors: R
authors: R
authors: Johnson
authors: Department of Academic Surgery, University Hospital of South Manchester, Manchester.
authors: K
authors: K
authors: Cheema
authors: Department of Medical Statistics.
authors: J
authors: J
authors: Morris
authors: Department of Histopathology, University Hospital of South Manchester, Manchester, UK.
authors: M
authors: M
authors: Howe
authors: Department of Academic Surgery, University Hospital of South Manchester, Manchester. Electronic address: bundredn@manchester.ac.uk.
authors: N J
authors: NJ
authors: Bundred
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D004739:England; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: DCIS; Luminal A; molecular phenotype; recurrence