Clonal profiling of mixed lobular and ductal carcinoma revealed by multiplex ligation‐dependent probe amplification and fluorescence in situ hybridization

A needle biopsy of a mass in the right breast of a 36‐year‐old woman revealed invasive ductal carcinoma (IDC), and approximately 20% of cancer cells showed unequivocal membranous staining with the HercepTest. After systemic therapy with trastuzumab and paclitaxel followed by FEC (fluorouracil + epirubicin + cyclophosphamide), a right mastectomy was performed. By histological and immunohistochemical examinations, the resected tumor consisted mainly of E‐cadherin‐negative invasive lobular carcinoma (ILC), and the rest was ERBB2‐positive IDC; thus, the diagnosis was mixed ductal and lobular carcinoma. Multiplex ligation‐dependent probe amplification and fluorescence in situ hybridization (FISH) analyses revealed that ILC and IDC shared high‐level amplification of CCND1 in homogeneously staining regions (HSR) and that IDC had an additional HSR‐type amplicon of ERBB2. These findings strongly indicate that IDC and ILC had a common precursor cell with CCND1 amplification. Review of the biopsy specimen with FISH showed IDC with gene amplifications of CCND1 and ERBB2 as a minor component, IDC without amplification of CCND1 or ERBB2 as a major component, and a minute portion of ILC with CCND1 amplification. We speculate that chemotherapy and trastuzumab caused a marked reduction in IDC; however, ILC with CCND1 amplification was resistant to chemotherapy and grew.