Clonal alteration of breast cancer receptors between primary ductal carcinoma in situ (DCIS) and corresponding local events

Eur J Cancer. 2014 Feb;50(3):517-24. doi: 10.1016/j.ejca.2013.10.020. Epub 2013 Nov 22.

Abstract

Background: Emerging data propose biomarker alteration due to clonal selection between the primary invasive breast cancer and corresponding metastases. In addition, impact on survival has been demonstrated. The present study investigates the relationship between the oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) between primary ductal carcinoma in situ (DCIS) and intra-individually matched ipsilateral event.

Materials and methods: The cohort includes 1504 patients, diagnosed with a primary DCIS between 1986 and 2004. Of the 274 patients who developed a local relapse, 135 developed a new in situ carcinoma and 139 an invasive cancer up to 31st December 2011. ER and PR were identified by immunohistochemistry (IHC) and HER2 by silver-enhanced in situ hybridisation (SISH) as well as IHC.

Results: ER (n=112), PR (n=113) and HER2 (n=114) status from both the primary DCIS and the corresponding relapse were assessed and were demonstrated to be discordant in 15.1%, 29.2% and 10.5% respectively. The receptor conversion was both from negative to positive and from positive to negative with no general pattern being seen in spite of sub-dividing into in situ relapse and invasive relapse. However, primary DCIS was HER2 positive in 40.3% whereas in situ and invasive relapses were HER2 positive in 42.9% and 34.5% respectively.

Conclusions: Receptor conversion for ER, PR and HER2 status occurred between primary DCIS and corresponding local relapse in 10-30%. This study could not confirm that HER2 overexpression in primary DCIS had any impact on tumour progression to invasive cancer which has been proposed.

Keywords: Breast cancer; DCIS; Ductal carcinoma in situ; ER; HER2; Hormonal receptor; Human epidermal growth factor receptor 2; Oestrogen receptor; PR; Progesterone receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Intraductal, Noninfiltrating / genetics
  • Carcinoma, Intraductal, Noninfiltrating / metabolism*
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Clone Cells
  • Cohort Studies
  • Female
  • Humans
  • Middle Aged
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2