Clinical Response to a Lapatinib-Based Therapy for a Li-Fraumeni Syndrome Patient with a Novel

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) identifi ed oncogenic alterations in the HER2 and EGFR genes across all tumors, including HER2 amplifi cations, an EGFR -exon 20 insertion, and the fi rst-in-humans HER2 V659E muta- tion showing a phenotypic convergent evolution toward HER2 and EGFR alterations. Following the identifi cation 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. HER2 V659E sensitivity to lapatinib was confi rmed 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 preva- lence of HER2 and EGFR genomic alterations. Cancer Discov; 3(11); 1-7. ©2013 AACR.