title: Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer.
abstract: BACKGROUND
  At least four major categories of invasive breast cancer that are associated with different clinical outcomes have been identified by gene expression profiling: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and basal-like. However, the prevalence of these phenotypes among cases of ductal carcinoma in situ (DCIS) has not been previously evaluated in detail. The purpose of this study was to compare the prevalence of these distinct molecular subtypes among cases of DCIS and invasive breast cancer.
  
  
  METHODS
  We constructed tissue microarrays (TMAs) from breast cancers that developed in 2897 women enrolled in the Nurses' Health Study (1976 to 1996). TMA slides were immunostained for oestrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR). Using these immunostain results, cases were grouped into molecularly defined subtypes.
  
  
  RESULTS
  The prevalence of the distinct molecular phenotypes differed significantly between DCIS (n = 272) and invasive breast cancers (n = 2249). The luminal A phenotype was significantly more frequent among invasive cancers (73.4%) than among DCIS lesions (62.5%) (p = 0.0002). In contrast, luminal B and HER2 molecular phenotypes were both more frequent among DCIS (13.2% and 13.6%, respectively) as compared with invasive tumours (5.2% and 5.7%, respectively) (p < 0.0001). The basal-like phenotype was more frequent among the invasive cancers (10.9%) than DCIS (7.7%), although this difference was not statistically significant (p = 0.15). High-grade DCIS and invasive tumours were more likely to be HER2 type and basal-like than low- or intermediate-grade lesions. Among invasive tumours, basal-like and HER2 type tumours were more likely to be more than 2 cm in size, high-grade and have nodal involvement compared with luminal A tumours.
  
  
  CONCLUSIONS
  The major molecular phenotypes previously identified among invasive breast cancers were also identified among cases of DCIS. However, the prevalence of the luminal A, luminal B and HER2 phenotypes differed significantly between DCIS and invasive breast cancers.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA. Rulla.Tamimi@channing.harvard.edu
authors.forename: Rulla M
authors.initials: RM
authors.lastname: Tamimi
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Baer
authors.forename: Jonathan
authors.initials: J
authors.lastname: Marotti
authors.forename: Mark
authors.initials: M
authors.lastname: Galan
authors.forename: Laurie
authors.initials: L
authors.lastname: Galaburda
authors.forename: Yineng
authors.initials: Y
authors.lastname: Fu
authors.forename: Anne C
authors.initials: AC
authors.lastname: Deitz
authors.forename: James L
authors.initials: JL
authors.lastname: Connolly
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Schnitt
authors.forename: Graham A
authors.initials: GA
authors.lastname: Colditz
authors.forename: Laura C
authors.initials: LC
authors.lastname: Collins
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D015995:Prevalence; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D007633:Keratins; D066246:ErbB Receptors