Abstract
BackgroundPatients with DNA-damage response genes (DDR)-related pancreas cancer (BRCA1/2 or other DNA-damage related genes) may have improved outcomes secondary to increased sensitivity to DNA-damaging drugs (platinum chemotherapy/ poly ADP ribose polymerase (PARP)-inhibitors). However, data is scarce pertaining to outcomes in this subset of patients. Our objective was to retrospectively identify DDR-related pancreas cancer patients and report on clinical outcomes.MethodsPancreas cancer patients with a germline pathogenic variant in BRCA1/2 or other DDR gene were identified retrospectively through review of medical records (medical genetics/oncology) and genetic testing results at our institution. Data regarding clinical outcomes, therapy received, and survival was subsequently extracted.ResultsA total of 11 patients with pancreas cancer were identified to carry a pathogenic DDR-variant: BRCA1 (3), ATM (4), BRCA2 (2), PALB2 (1) and FANCC (1). Five of these individuals had prior history of other cancers. Clinically these tumors were localized (4), locally advanced (3), and metastatic (4) at diagnosis. Four out of 11 patients were still alive at time of data review. Survival in the 7 patients who had died was 13.7, 140.0, 20.5, 22.3, 23.5, 25.8, and 111.5 months. All patients with advanced disease had exposure to platinum chemotherapy.ConclusionsHistorical survival in patients with advanced and metastatic pancreas cancer is poor. Results of this DDR-subset of patients do show significantly superior outcomes, likely secondary to exposure to platinum drugs. This data, alongside other similar cohorts, would favor the DDR-genes being a predictive marker with improved survival if exposed to these drugs and the new class of drugs, PARP-inhibitors.
Highlights
Patients with DNA-damage response genes (DDR)-related pancreas cancer (BRCA1/2 or other DNAdamage related genes) may have improved outcomes secondary to increased sensitivity to DNA-damaging drugs (platinum chemotherapy/ poly ADP ribose polymerase (PARP)-inhibitors)
Treatment alterations can be considered if a cancer shows mismatch repair (MMR) or DNA damage repair (DDR) deficiency [2,3,4,5]
Pathogenic variants detected were within BRCA1 [2], ATM [3], BRCA2 [4], PALB2 [1] and FANCC [1]
Summary
Patients with DNA-damage response genes (DDR)-related pancreas cancer (BRCA1/2 or other DNAdamage related genes) may have improved outcomes secondary to increased sensitivity to DNA-damaging drugs (platinum chemotherapy/ poly ADP ribose polymerase (PARP)-inhibitors). Our objective was to retrospectively identify DDR-related pancreas cancer patients and report on clinical outcomes. Germline testing for hereditary cancer syndromes was completed largely to provide guidance for future surveillance and provided little to no clinical utility for those already affected with pancreatic cancer. Developments in our understanding of pancreatic cancer pathology opened additional applications for genetic results. Germline and somatic results can influence management recommendations and possibly general prognosis as well. Individuals with a DDR-related cancer can include those with a pathogenic, germline or somatic BRCA1/2 variant and other genes within the homologous recombination and Fanconi anemia
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