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Naama Halpern,1,2 Albert Grinshpun,3 Ben Boursi,1,2 Talia Golan,1,2 Ofer Margalit,1,2 Dan Aderka,1,2 Eitan Friedman,2,4 Yael Laitman,2,3 Ayala Hubert,3 Luna Kadouri,3 Tamar Hamburger,3 Inbal Barnes-Kedar,2,5 Zohar Levi,2,6 Irit Ben-Aharon,2,7 Baruch Brenner,2,7 Yael Goldberg,2,5 Tamar Peretz,3 Einat Shacham-Shmueli1,2 1Department of Oncology, Sheba Medical Center, Tel-Hashomer, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 4The Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer, Israel; 5Recanati Genetics Institute, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel; 6Division of Gastroenterology, Rabin Medical Center, Early Detection and High Risk Unit, Petach Tikva, Israel; 7Institute of Oncology, Davidoff Center, Rabin Medical Center, Petach Tikva, IsraelCorrespondence: Naama HalpernDepartment of Oncology, Sheba Medical Center, Tel-Hashomer, Rmat Gan, IsraelTel +972-3-530-2668Fax +972-3-5304958Email naama.halpern@sheba.gov.ilBackground: The prognosis of gastric cancer (GC) is poor with a median overall survival (OS) of less than 12 months in advanced-stage disease. The search for distinct genetic subgroups of GC patients and predictive biomarkers is ongoing. While BRCA1 or BRCA2 germline mutations (gBRCAm) have potential therapeutic implications in ovarian, breast and pancreatic cancers, their significance in GC patients has not been established.Patients and Methods: A retrospective multi-center data analysis of GC patients with gBRCAm was conducted, detailing the clinical characteristics and disease course in this unique subset of patients.Results: Ten GC patients with gBRCAm were identified, six of them with metastatic disease. The median OS of all ten GC patients was 47.5 (13– 192) months. Median OS for patients diagnosed with operable disease was 55.5 (13– 192) months and of the patients with metastatic disease (calculated from metastatic disease diagnosis) 32 (15– 52) months with an exceptional 1-, 2- and 3-year survival rate of 100%, 83.3% and 50%, respectively.Conclusion: These preliminary data suggest that gBRCAm in GC patients are associated with a favorable prognosis. Furthermore, gBRCAm might be a predictive biomarker to DNA-damaging agents response in GC patients, similarly to its established role in other malignancies. Further research is needed to confirm our findings.Keywords: gastric cancer, BRCA1, BRCA2, DNA-damaging agents, PARP inhibitors |
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