Work

Prolonged overall survival of metastatic gastric cancer patients with BRCA germline mutations

Year: 2018

Type: article

Abstract: Introduction: Gastric cancer is the fifth most frequently diagnosed malignancy worldwide and the third leading cause of cancer related death. The prognosis of gastric cancer remains poor with median overall survival rates of less than 12 months in the advanced setting. Significant efforts are made to identify prognostic and predictive markers to tailor treatment decisions. BRCA1 and BRCA 2 germline mutations are an established predictive marker to a favorable response to DNA-damaging agents (platinum agents and Poly(ADP-ribose)polymerase inhibitors) in ovarian, breast prostate and pancreatic cancers. There is limited clinical data in regard to the efficacy of DNA-damaging agents on BRCA germline mutation carriers with gastric cancer. Methods: A multi-center retrospective analysis of genetic databases and patient’s files was performed in three medical centers to identify consecutive BRCA1/2 germline mutation carriers with gastric adenocarcinomas between the years 1994 to 2018. Patient's characteristics and disease course were collected and summarized. Results: Nine BRCA1/2 carriers with gastric adenocarcinomas were identified. Five of them were females. Six patients were from an Ashkenazi origin. Seven patients had BRCA2 mutation. Three patients had a personal history of a second malignancy. Two patients had a first-degree family member with gastric cancer. Mean age at diagnosis was 64 (range of 52-74 years). One patient demonstrated positive HER2 staining (IHC +3) in her tumor. We did not identify unique patterns in term of tumor location or histology. Six patients had metastatic disease. Five patients with metastatic disease received DNA-damaging agents. The median overall survival of the six metastatic patients was 25 months (range 13-43), three of them have ongoing durable responses. Conclusion: Germline BRCA1/2 mutations are associated with a relatively favorable prognosis in gastric cancer patients treated with DNA-damaging agents. Some patients in our cohort had a first degree relative with gastric cancer, possibly indicating a unique phenotype in some BRCA families. Further research is needed to determine the characteristics and long-term outcome of these patients.

Source: Annals of Oncology

DOI: 10.1093/annonc/mdy151.054