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Cancer Discov. 2013 Nov;3(11):1238-44. doi: 10.1158/2159-8290.CD-13-0132. Epub 2013 Aug 15.

Clinical response to a lapatinib-based therapy for a Li-Fraumeni syndrome patient with a novel HER2V659E mutation.

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1Vall d'Hebron Institut d'Oncologia; 2Vall d'Hebron Institut de Recerca; 3Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona; 4Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain; and 5Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York.


Genomic characterization of recurrent breast and lung tumors developed over the course of 10 years in a 29-year-old patient with a germline TP53 mutation (Li-Fraumeni Syndrome) identified oncogenic alterations in the HER2 and EGFR genes across all tumors, including HER2 amplifications, an EGFR-exon 20 insertion, and the first-in-humans HER2V659E mutation showing a phenotypic convergent evolution toward HER2 and EGFR alterations. Following the identification of HER2-activating events in the most recent lung carcinoma and in circulating tumor cells, we treated the reminiscent metastatic lesions with a lapatinib-based therapy. A symptomatic and radiologic clinical response was achieved. HER2V659E sensitivity to lapatinib was confirmed in the laboratory.


The precise knowledge of the genomic alterations present in tumors is critical to selecting the optimal treatment for each patient. Here, we report the molecular characterization and clinical response to a lapatinib-based therapy for the tumors of a Li-Fraumeni patient showing prevalence of HER2 and EGFR genomic alterations.

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