HER2/neu and Ki-67 expression predict non-invasive recurrence following breast-conserving therapy for ductal carcinoma in situ

Br J Cancer. 2012 Mar 13;106(6):1160-5. doi: 10.1038/bjc.2012.41. Epub 2012 Feb 23.


Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer that may progress to invasive cancer. Identification of factors that predict recurrence and distinguish DCIS from invasive recurrence would facilitate treatment recommendations. We examined the prognostic value of nine molecular markers on the risks of local recurrence (DCIS and invasive) among women treated with breast-conserving therapy.

Methods: A total of 213 women who were treated with breast-conserving therapy between 1982 and 2000 were included; 141 received breast-conserving surgery alone and 72 cases received radiotherapy. We performed immunohistochemical staining on the DCIS specimen for nine markers: oestrogen receptor, progesterone receptor, Ki-67, p53, p21, cyclinD1, HER2/neu, calgranulin and psoriasin. We performed univariable and multivariable survival analyses to identify markers associated with the recurrence.

Results: The rate of recurrence at 10 years was 36% for patients treated with breast-conserving surgery alone and 18% for women who received breast-conserving surgery and radiotherapy. HER2/neu+/Ki-67+ expression was associated with an increased risk of DCIS recurrence, independent of grade and age (HR=3.22; 95% CI: 1.47-7.03; P=0.003). None of the nine markers were predictive of invasive recurrence.

Conclusion: Women with a HER2/neu/neu+/Ki67+ DCIS have a higher risk of developing DCIS local recurrence after breast-conserving surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Carcinoma, Intraductal, Noninfiltrating / metabolism*
  • Carcinoma, Intraductal, Noninfiltrating / mortality
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Carcinoma, Intraductal, Noninfiltrating / surgery
  • Cohort Studies
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism*
  • Mastectomy, Segmental
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local*
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Treatment Outcome


  • Biomarkers, Tumor
  • Ki-67 Antigen
  • ERBB2 protein, human
  • Receptor, ErbB-2