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Background  Lobular carcinoma  in situ  (LCIS) is a non-invasive breast lesion that is typically found incidentally on biopsy and is often associated with invasive lobular carcinoma (ILC). LCIS is considered by some to be a risk factor for future breast cancer rather than a true precursor lesion. The aim of this study was to identify genetic changes that could be used as biomarkers of progression of LCIS to invasive disease using cases of pure LCIS and comparing their genetic profiles to LCIS which presented contemporaneously with associated ILC, on the hypothesis that the latter represents LCIS that has already progressed.    Methods  Somatic copy number aberrations (SCNAs) were assessed by SNP array in three subgroups: pure LCIS, LCIS associated with ILC and the paired ILC. In addition exome sequencing was performed on seven fresh frozen samples of LCIS associated with ILC, to identify recurrent somatic mutations.    Results  The copy number profiles of pure LCIS and LCIS associated with ILC were almost identical. However, four SCNAs were more frequent in ILC than LCIS associated with ILC, including gain/amplification of  CCND1.  CCND1 protein over-expression assessed by immunohistochemical analysis in a second set of samples from 32 patients with pure LCIS and long-term follow up, was associated with invasive recurrence ( P  = 0.02, Fisher’s exact test). Exome sequencing revealed that  PIK3CA  mutations were as frequent as  CDH1  mutations in LCIS, but were not a useful biomarker of LCIS progression as they were as frequent in pure LCIS as in LCIS associated with ILC. We also observed heterogeneity of  PIK3CA  mutations and evidence of sub-clonal populations in LCIS irrespective of whether they were associated with ILC.    Conclusions  Our data shows that pure LCIS and LCIS co-existing with ILC have very similar SCNA profiles, supporting the hypothesis that LCIS is a true precursor lesion. We have provided evidence that over-expression of CCND1 may identify a subgroup of patients with pure LCIS who are more likely to develop invasive disease, in contrast to  PIK3CA  mutations, which occur too early in lobular tumorigenesis to be informative.    Electronic supplementary material  The online version of this article (doi:10.1186/s13058-016-0789-y) contains supplementary material, which is available to authorized users.

PIK3CA mutations are common in lobular carcinoma in situ, but are not a biomarker of progression