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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.

Author information

1
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.

Abstract

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.

SIGNIFICANCE:

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.

PMID:
23950206
DOI:
10.1158/2159-8290.CD-13-0132
[Indexed for MEDLINE]
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