An emerging entity: Pancreatic adenocarcinoma associated with a known brca mutation: Clinical descriptors, treatment implications, and future directions Journal Article
| Authors: | Lowery, M. A.; Kelsen, D. P.; Stadler, Z. K.; Yu, K. H.; Janjigian, Y. Y.; Ludwig, E.; D'adamo, D. R.; Salo-Mullen, E.; Robson, M. E.; Allen, P. J.; Kurtz, R. C.; O'Reilly, E. M. |
| Article Title: | An emerging entity: Pancreatic adenocarcinoma associated with a known brca mutation: Clinical descriptors, treatment implications, and future directions |
| Abstract: | 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 aBRCA1(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. © AlphaMed Press. |
| Keywords: | adult; clinical article; controlled study; middle aged; gene mutation; genetics; cisplatin; fluorouracil; systemic therapy; capecitabine; gemcitabine; cancer radiotherapy; pancreatic neoplasms; temozolomide; antineoplastic agent; adenocarcinoma; metastasis; breast cancer; genetic association; docetaxel; irinotecan; oncogene; tumor suppressor gene; genes, brca1; genes, brca2; folinic acid; drug response; pancreas adenocarcinoma; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; flavopiridol; platinum complex; oxaliplatin; acinar cell carcinoma; jews; brca1; brca2; germ-line mutation; pancreas surgery; parp |
| Journal Title: | The Oncologist |
| Volume: | 16 |
| Issue: | 10 |
| ISSN: | 1083-7159 |
| Publisher: | Oxford University Press |
| Date Published: | 2011-01-01 |
| Start Page: | 1397 |
| End Page: | 1402 |
| Language: | English |
| DOI: | 10.1634/theoncologist.2011-0185 |
| PROVIDER: | scopus |
| PUBMED: | 21934105 |
| PMCID: | PMC3228075 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 9 December 2011" - "CODEN: OCOLF" - "Source: Scopus" |
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