Evidence that Coexistent Synchronous Ipsilateral Lobular & Ductal Carcinoma are Related Clonal Processes

Background Biopsy‐proved in situ lobular carcinoma (LCIS) portends increased risk for subsequent invasive carcinoma, which often has a ductal phenotype. A plausible explanation is that such in situ (DCIS) & invasive ductal carcinoma (InvDC) is not a separate neoplastic process but is genetically related to LCIS. If true, we expect coexistent lobular & ductal carcinoma to have highly concordant genomic profiles. To test this hypothesis, we compared DNA abnormalities, as defined by array comparative genomic hybridization (aCGH), in concurrent LCIS, DCIS &, in some cases, InvDC. Design We used a 6,912 BAC clone microarray to identify & map gains & losses in DNA from cells microdissected from paraffin embedded tissues (PETs). Using our new aCGH pre‐processing software, specifically adapted to PETs, we calculated the number of concordant clone specific changes in each component of synchronous LCIS & DCIS (N=4) & LCIS, DCIS & InvDC (N=3). Results There were many concordant clone specific gains & losses in coexistent LCIS, DCIS & InvDC in each patient; similarity was much higher between different components within a patient than between patients. Conclusion Despite the clearly different morphologic appearances that have conventionally defined them, LCIS, DCIS & InvDC occurring in the same breast are not independent events but arise from a common abnormal progenitor. In part funded under a grant from the Pennsylvania Department of Health which specifically disclaims responsibility for any analyses, interpretations or conclusions.