title: Clonality of lobular carcinoma in situ (LCIS) and metachronous invasive breast cancer.
abstract: 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.
authors: Department of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany. sebastian_aulmann@med.uni-heidelberg.de
authors: Sebastian
authors: S
authors: Aulmann
authors: Roland
authors: R
authors: Penzel
authors: Thomas
authors: T
authors: Longerich
authors: Benjamin
authors: B
authors: Funke
authors: Peter
authors: P
authors: Schirmacher
authors: Hans Peter
authors: HP
authors: Sinn
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D015820:Cadherins / Q000032:analysis; D002278:Carcinoma in Situ / Q000235:genetics / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000235:genetics / Q000473:pathology*; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000473:pathology*
chemical_list: D015820:Cadherins; D004272:DNA, Mitochondrial