title: Risk of subsequent in situ and invasive breast cancer in human epidermal growth factor receptor 2-positive ductal carcinoma in situ.
abstract: BACKGROUND
  To assess the prognostic role of human epidermal growth factor receptor 2 (HER2) overexpression in patients with ductal carcinoma in situ (DCIS).
  
  
  METHODS
  We identified patients with HER2-positive DCIS among a population of 1667 cases, prospectively diagnosed and surgically treated at the European Institute of Oncology from 1996 to 2008. Rates of subsequent DCIS or invasive cancer in HER2-positive disease were estimated. We evaluated Cumulative Incidence of In Situ Breast Cancer Recurrence (isBCR), INvasive Breast Cancer Recurrence (IBCR) and any Breast Cancer Recurrence (BCR). isBCR, IBCR and BCR were defined as the time from surgery to breast cancer recurrence as first event (in situ, invasive or both, respectively) or last visit in case of no events.
  
  
  RESULTS
  We identified 560 (33.5%) patients with HER2-positive DCIS. The median follow-up was 7.6 years (interquartile range 5.9-9.5). We observed 422 events out of 1667 patients, with 141 in situ recurrences, 201 invasive recurrences and 80 other events (64 second primaries and 16 deaths). The 10-year isBCR proportions were 11.8% [95% confidence interval (CI) 9.0% to 15.4%] in the HER2-positive group and 8.8% (95% CI 6.9% to 11.0%) in the HER2-negative group (Gray test, P = 0.010). At multivariable analysis, the adjusted risk of isBCR was higher in the HER2-positive group than in the HER2-negative group [hazard ratio (HR) HER2 positive versus negative: 1.59 (95% CI 1.06-2.39)]. We observed significant differences both in BCR and isBCR for patients treated by quadrantectomy without radiotherapy versus patients treated with radiotherapy [adjusted HR HER2 positive versus negative: 1.53 (95% CI 1.07-2.18) and adjusted HR HER2 positive versus negative: 2.18 (95% CI 2.18-3.69), respectively].
  
  
  CONCLUSIONS
  HER2 overexpression predicts an increased risk of isBCR. Radiotherapy reduces local failure rates in HER2-positive DCIS.
authors.affiliation: Division of Experimental Therapeutics. Electronic address: giuseppe.curigliano@ieo.it.
authors.forename: G
authors.initials: G
authors.lastname: Curigliano
authors.affiliation: Division of Epidemiology and Biostatistics.
authors.forename: D
authors.initials: D
authors.lastname: Disalvatore
authors.affiliation: Division of Experimental Therapeutics.
authors.forename: A
authors.initials: A
authors.lastname: Esposito
authors.affiliation: Department of Pathology and Laboratory Medicine; School of Medicine, University of Milano, Milan.
authors.forename: G
authors.initials: G
authors.lastname: Pruneri
authors.affiliation: Division of Cancer Prevention and Genetics.
authors.forename: M
authors.initials: M
authors.lastname: Lazzeroni
authors.affiliation: Division of Cancer Prevention and Genetics.
authors.forename: A
authors.initials: A
authors.lastname: Guerrieri-Gonzaga
authors.affiliation: Division of Senology.
authors.forename: A
authors.initials: A
authors.lastname: Luini
authors.affiliation: School of Medicine, University of Milano, Milan; Department of Medical Imaging and Radiation Sciences.
authors.forename: R
authors.initials: R
authors.lastname: Orecchia
authors.affiliation: Breast Health Program, European Institute of Oncology, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
authors.affiliation: Division of Epidemiology and Biostatistics.
authors.forename: N
authors.initials: N
authors.lastname: Rotmensz
authors.affiliation: Division of Cancer Prevention and Genetics.
authors.forename: B
authors.initials: B
authors.lastname: Bonanni
authors.affiliation: Department of Pathology and Laboratory Medicine; School of Medicine, University of Milano, Milan.
authors.forename: G
authors.initials: G
authors.lastname: Viale
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: ductal carcinoma in situ; epidermal growth factor receptor 2 (HER2) overexpression