Breast Cancer Research and Treatment

, Volume 107, Issue 3, pp 331–335

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


    • Department of PathologyUniversity of Heidelberg
  • Roland Penzel
    • Department of PathologyUniversity of Heidelberg
  • Thomas Longerich
    • Department of PathologyUniversity of Heidelberg
  • Benjamin Funke
    • Department of PathologyUniversity of Heidelberg
  • Peter Schirmacher
    • Department of PathologyUniversity of Heidelberg
  • Hans Peter Sinn
    • Department of PathologyUniversity of Heidelberg
Preclinical Study

DOI: 10.1007/s10549-007-9557-0

Cite this article as:
Aulmann, S., Penzel, R., Longerich, T. et al. Breast Cancer Res Treat (2008) 107: 331. doi:10.1007/s10549-007-9557-0


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 cancerClonalityLobular carcinoma in situ (LCIS)Mitochondrial DNA heteroplasmy

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© Springer Science+Business Media, LLC 2007