title: Expression of HER2neu in ductal carcinoma in situ is associated with local recurrence.
abstract: OBJECTIVE
  Determination of the risk of recurrence after local excision of ductal carcinoma in situ (DCIS) remains a challenge. Molecular profiling based on immunohistochemical staining to oestrogen receptor (ER), progesterone receptor (PR) and HER2neu improved risk prediction in invasive breast cancer, but few studies have evaluated if molecular classification of DCIS predicts local recurrence. We evaluated the expression of ER, PR and HER2neu in DCIS to determine if molecular classification predicts local recurrence after breast-conserving therapy for DCIS.
  
  
  METHODS
  We reviewed the records of patients with DCIS treated between 1987 and 2000, carried out a pathology review and immunohistochemical staining for ER, PR and HER2neu and categorised cases into four molecular phenotypes [luminal A (ER+ and/or PR+, HER2neu-), luminal B (ER+ and/or PR+, HER2neu+), HER2neu subtype (ER-, PR-, HER2neu+), triple negative (ER-, PR-, HER2neu-)]. We evaluated the association between the molecular subtype and the development of local recurrence.
  
  
  RESULTS
  In total, 180 cases of DCIS were included in the study (luminal A, n=113; luminal B, n=25; HER2neu type, n=29; triple negative, n=13). The median follow-up time was 8.7 years. We observed higher rates of local recurrence among luminal B (40%) and HER2neu type (38%) DCIS compared with luminal A (21%) and triple negative (15%) DCIS. On multivariable analysis, HER2neu overexpression was associated with an increased risk of local recurrence (hazard ratio=1.98; 95% confidence interval: 1.11, 3.53, P=0.02).
  
  
  CONCLUSIONS
  HER2neu expression in DCIS is a significant predictor of local recurrence, whereas luminal A and triple negative phenotypes are associated with relatively low risks of local recurrence.
authors.affiliation: Department of Radiation Oncology, University of Toronto, Toronto, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Han
authors.forename: S
authors.initials: S
authors.lastname: Nofech-Mozes
authors.forename: S
authors.initials: S
authors.lastname: Narod
authors.forename: W
authors.initials: W
authors.lastname: Hanna
authors.forename: D
authors.initials: D
authors.lastname: Vesprini
authors.forename: R
authors.initials: R
authors.lastname: Saskin
authors.forename: C
authors.initials: C
authors.lastname: Taylor
authors.forename: I
authors.initials: I
authors.lastname: Kong
authors.forename: L
authors.initials: L
authors.lastname: Paszat
authors.forename: E
authors.initials: E
authors.lastname: Rakovitch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone