Clinical response to a lapatinib-based therapy of a Li-Fraumeni Syndrome patient with a novel HER2-V659E mutation

Clinical response to a lapatinib-based therapy of a Li-Fraumeni Syndrome patient with a novel HER2-V659E mutation

1. Violeta Serra1,
2. Ana Vivancos2,
3. Xose S Puente3,
4. Enriqueta Felip4,
5. Daniel Silberschmidt5,
6. Ginevra Caratu5,
7. Josep Lluis Parra6,
8. Leticia De Mattos-Arruda7,
9. Judit Grueso8,
10. Javier Hernandez-Losa9,
11. Joaquin Arribas10,
12. Ludmila Prudkin11,
13. Paolo Nuciforo12,
14. Maurizio Scaltriti13,
15. Joan Seoane14 and
16. Jose Baselga15,*

+ Author Affiliations

1. ¹Experimental Therapeutics Group, Vall d'Hebron Institute of Oncology
2. ²Oncology, Vall d'Hebron Institute of Oncology
3. ³Dpt. Bioquimica y Biologia Molecular, IUOPA-Universidad de Oviedo
4. ⁴Thoracic Tumors Group, Vall d'Hebron Institute of Oncology
5. ⁵Cancer Genomics Group, Vall d'Hebron Institute of Oncology
6. ⁶Medical Oncology Research Program, Vall d'Hebron Insitute of Oncology
7. ⁷Translational Research Program, Medical Oncology Department, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital
8. ⁸Experimental Therapeutics Laboratory, Vall d'Hebron Institute of Oncology (VHIO)
9. ⁹Pathology, Fundacio Insitut de Recerca. Vall d'Hebron University Hospital
10. ¹⁰Pre-Clinical Research, Vall d'Hebron Insitute of Oncology
11. ¹¹Molecular Pathology, Vall d'Hebron University Hospital
12. ¹²Molecular Oncology Group, Vall d'Hebron Institute of Oncology
13. ¹³Human Oncology & Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center
14. ¹⁴Vall d'Hebron Institute of Oncology Barcelona, Spain
15. ¹⁵Human Oncology and Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center

1. ↵* Corresponding Author:
   Jose Baselga, Human Oncology and Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, NY, 10065, United States baselgaj@mskcc.org

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 p53 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-human HER2-V659E mutation showing a phenotypic convergent evolution towards 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 clinical response both symptomatic and radiologic was achieved. HER2-V659E sensitivity to lapatinib was confirmed in the laboratory.

• Received March 26, 2013.
• Revision received July 11, 2013.
• Accepted August 6, 2013.

• Copyright © 2013, American Association for Cancer Research.