期刊
ONCOLOGIST
卷 16, 期 10, 页码 1397-1402出版社
WILEY
DOI: 10.1634/theoncologist.2011-0185
关键词
BRCA1; BRCA2; Pancreas adenocarcinoma; Genetics; PARP
类别
资金
- Boehringer Ingelheim
- Bayer
- Genentech
- AstraZeneca
- KuDos Pharmaceuticals
- Amgen
- sanofi-aventis
- Enzon
- Pfizer
- Bristol-Myers Squibb
- Methylgene
- Novartis
- Ardea
- Exelixis
- FibroGen
- Incyte
- ArQule
- GlaxoSmithKline
Background. BRCA1 and BRCA2 germline mutations are associated with an elevated risk for pancreas adenocarcinoma (PAC). Other BRCA-associated cancers have been shown to have greater sensitivity to platinum and poly (ADP-ribose) polymerase (PARP) inhibitors with better clinical outcomes than in sporadic cases; however, outcomes in BRCA-associated PAC have not been reported. Methods. Patients with a known BRCA1 or BRCA2 mutation and a diagnosis of PAC were identified from the Gastrointestinal Oncology Service, Familial Pancreas Cancer Registry, and Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center. Results. Fifteen patients, five male, with a BRCA1 (n = 4) or BRCA2 (n = 11) mutation and PAC and one patient with a BRCA1 mutation and acinar cell carcinoma of the pancreas were identified. Seven female patients (70%) had a prior history of breast cancer. Four patients received a PARP inhibitor alone or in combination with chemotherapy; three demonstrated an initial radiographic partial response by Response Evaluation Criteria in Solid Tumors whereas one patient had stable disease for 6 months. Six patients received platinum-based chemotherapy first line for metastatic disease; five of those patients had a radiographic partial response. Conclusion. BRCA mutation-associated PAC represents an underidentified, but clinically important, subgroup of patients. This is of particular relevance given the ongoing development of therapeutic agents targeting DNA repair, which may potentially offer a significant benefit to a genetically selected population. We anticipate that further study and understanding of the clinical and biologic features of BRCA-mutant PAC will aid in the identification of tissue biomarkers indicating defective tumor DNA repair pathways in sporadic PAC. The Oncologist 2011; 16: 1397-1402
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