Breast Cancer Research and Treatment

, Volume 107, Issue 3, pp 331–335 | Cite as

Clonality of lobular carcinoma in situ (LCIS) and metachronous invasive breast cancer

  • Sebastian Aulmann
  • Roland Penzel
  • Thomas Longerich
  • Benjamin Funke
  • Peter Schirmacher
  • Hans Peter Sinn
Preclinical Study


Lobular carcinoma in situ (LCIS) of the breast is generally considered an indicator for a bilaterally increased risk of invasive breast cancer (IBC). However, as recent studies suggested a clonal relationship between a subset of synchronous LCIS and invasive lobular carcinomas (ILC), we aimed to examine a possible precursor role for LCIS and IBC occurring in the same breast at a later time. Out of a consecutive series of 88 LCIS, nine patients developed IBC (5 ILC and 4 invasive ductal carcinomas) between 2 and 10 years after initial biopsy. For each case, mitochondrial DNA heteroplasmy was analyzed in normal mammary gland epithelia, LCIS and IBC by PCR, direct DNA sequencing and phylogenetic tree clustering. Two cases of LCIS and ILC showed identical patterns of heteroplasmy. In one further case, additional mtDNA mutations were present in the ILC following LCIS. The remaining two cases of ILC and all 4 IDC were clonally unrelated to the previously diagnosed LCIS. While the overall risk for the development of invasive breast cancer following LCIS is relatively low and the majority of cases are clonally unrelated, our data clearly show that some LCIS eventually do progress to ILC. Thus, LCIS represents both an indicator lesion for an increased risk of subsequent invasive breast cancer and in some cases a precursor of ILC.


Breast cancer Clonality Lobular carcinoma in situ (LCIS) Mitochondrial DNA heteroplasmy 



Part of this work was supported by a grant from the Heidelberg University (3542.2). The authors would like to thank A. Boenisch, S. Fendrich and W. Schmitz for excellent technical assistance.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Sebastian Aulmann
    • 1
  • Roland Penzel
    • 1
  • Thomas Longerich
    • 1
  • Benjamin Funke
    • 1
  • Peter Schirmacher
    • 1
  • Hans Peter Sinn
    • 1
  1. 1.Department of PathologyUniversity of HeidelbergHeidelbergGermany

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