title: Molecular subtypes in ductal carcinoma in situ of the breast and their relation to prognosis: a population-based cohort study.
abstract: BACKGROUND
  Different molecular subtypes of breast cancer have been identified based on gene expression profiling. Treatment suggestions based on an approximation of these subtypes by immunohistochemical criteria have been published by the St Gallen international expert consensus panel. Ductal carcinoma in situ (DCIS) can be classified into the same molecular subtypes. Our aim was to study the relation between these newly defined subtypes and prognosis in DCIS.
  
  
  METHODS
  TMA including 458 women from a population-based cohort with DCIS diagnosed 1986-2004 was used. Stainings for ER, PR, HER2 and Ki67 were used to classify the surrogate molecular subtypes according to the St Gallen criteria from 2011. The associations with prognosis were examined using Kaplan-Meier analyses and Cox proportional hazards regression models.
  
  
  RESULTS
  Surrogate molecular subtyping could be done in 381 cases. Mean follow up was 164 months. Of the classified DCIS 186 were Luminal A (48.8%), 33 Luminal B/HER2- (8.7%), 74 Luminal B/HER2+ (17.4%), 61 HER2+/ER- (16.0%) and 27 Triple Negative (7.1%). One hundred and two women had a local recurrence of which 58 were invasive. Twenty-two women had generalised disease, 8 without a prior local recurrence. We could not find a prognostic significance of the molecular subtypes other than a higher risk of developing breast cancer after more than 10 years of follow-up among women with a Triple Negative DCIS (OR 3.2; 95% CI 1.1-9.8).
  
  
  CONCLUSIONS
  The results from this large population-based cohort, with long-term follow up failed to demonstrate a prognostic value for the surrogate molecular subtyping of DCIS using the St Gallen criteria up to ten years after diagnosis. More than ten years after diagnosis Triple Negative DCIS had an elevated risk of recurrence.
authors.affiliation: Department of Surgical Science, Uppsala University, Uppsala SE-75105, Sweden. wenjing.zh@gmail.com.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhou
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Amini
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Fjällskog
authors.forename: Thomas
authors.initials: T
authors.lastname: Sollie
authors.forename: Henrik
authors.initials: H
authors.lastname: Lindman
authors.forename: Therese
authors.initials: T
authors.lastname: Sørlie
authors.forename: Carl
authors.initials: C
authors.lastname: Blomqvist
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wärnberg
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human