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

Abstract

UNLABELLED:

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.

• Authors: Violeta Serra, Ana Vivancos, Xose S Puente, Enriqueta Felip, Daniel Silberschmidt, Ginevra Caratù, Josep-Lluís Parra, Leticia De Mattos-Arruda, Judit Grueso, Javier Hernández-Losa, Joaquín Arribas, Ludmila Prudkin, Paolo Nuciforo, Maurizio Scaltriti, Joan Seoane, José Baselga
• Journal: Cancer discovery (Cancer Discov) Vol. 3 Issue 11 Pg. 1238-44 (Nov 2013) ISSN: 2159-8290 [Electronic] United States
• PMID: 23950206 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2013 AACR.

Chemical References

• Protein Kinase Inhibitors
• Quinazolines
• Lapatinib
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adult
• Exome
• Female
• Humans
• Lapatinib
• Li-Fraumeni Syndrome (drug therapy, genetics, metabolism, pathology)
• Mutation
• Neoplasm Metastasis
• Protein Kinase Inhibitors (therapeutic use)
• Quinazolines (therapeutic use)
• Receptor, ErbB-2 (genetics, metabolism)
• Signal Transduction (drug effects)
• Tumor Cells, Cultured