Complete Response to Chemotherapy in Metastatic Pancreatic Carcinoma Associated with Double Heterozygous Germline Mutation in BRCA2 and CHEK2 Genes – a Case Report

Česká verze

Authors: Natália Pazderová ¹; Veronika Urbán ²; Marek Makovník ³; Dušan Macák ⁴; Pavol Janega ⁵; Michal Chovanec ¹; Katarína Rejleková ¹; Jozef Mardiak ¹; Michal Mego ¹
Authors place of work: II. onkologická klinika LF UK a NOÚ Bratislava, Slovenská republika ¹; Oddelenie lekárskej genetiky, NOÚ Bratislava, Slovenská republika ²; Rádiologické oddelenie, NOÚ Bratislava, Slovenská republika ³; Oddelenie patologickej anatómie, NOÚ Bratislava, Slovenská republika ⁴; Ústav patologickej anatómie, LF UK Bratislava, Slovenská republika ⁵
Published in the journal: Klin Onkol 2020; 33(3): 220-225
Category: Kazuistika
doi: https://doi.org/10.14735/amko2020220

Summary

Background: Metastatic pancreatic carcinoma is an aggressive disease with adverse prognosis. Despite slight advances in chemotherapy, complete remission of the disease is extremely rare.

Case: In this article we present a case of a patient with initially metastatic pancreatic adenocarcinoma, associated with double heterozygous germline mutation in BRCA2 and CHEK2 genes, with the description of clinical, radiological and histomorphological characteristics of the disease as well as the diagnostic and therapeutic procedure.

Results: The patient with initially metastatic pancreatic adenocarcinoma with multiple liver involvement achieved complete remission following first-line FOLFIRINOX chemotherapy. The treatment lasted for 12 months but due to increased neurotoxicity since the 9^th cycle, oxaliplatin was excluded from the regimen. Given the family history of several malignancies (prostate cancer, seminoma), genetic testing was performed, which confirmed heterozygous germline mutations in BRCA2 and CHEK2 genes. Since the treatment has been completed, the patient remains in complete remission at 30 months.

Conclusion: Given the low incidence of complete remissions in patients with metastatic pancreatic cancer, the further therapeutic approach is not clearly established, an individual treatment is important. Universal genetic testing is recommended in patients with pancreatic cancer as it may affect the treatment strategy.

Keywords:

Chemotherapy – BRCA2 – CHEK2 – Pancreatic cancer – germline mutation – remission – DNA repair

Zdroje

1. Hlodáková V, Safaei Diba C. Incidencia zhubných nádorov v Slovenskej republike 2011. Bratislava: Vydavateľstvo NCZI 2018.

2. McGuigan A, Kelly P, Turkington RC et al. Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol 2018; 24 (43): 4846–4861. doi: 10.3748/wjg.v24.i43.4846.

3. Kašperová B, Jurišová S, Macúch J et al. Undifferentiated carcinoma of the pancreas – a case report. Klin Onkol 2018; 31 (6): 453–456. doi: 10.14735/amko2018453.

4. Conroy T, Desseigne F, Ychou M et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364 (19): 1817–1825. doi: 10.1056/nejmoa1011923.

5. Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F et al. Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol 2013; 31 (1): 23–29. doi: 10.1200/jco.2012.44.4869.

6. Von Hoff DD, Ervin T, Arena FP et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369 (18): 1691–1703. doi: 10.1056/nejmoa1304369.

7. NCCN Clinical practice guidelines in oncology – pancreatic adenocarcinoma, [online]. Available from: https: //www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf.

8. Sonnenblick A, Kadouri L, Appelbaum Liat et al. Complete remission in BRCA2 mutation carrier with metastatic pancreatic adenocarcinoma, treated with cisplatin based therapy. Cancer Biol Ther 2011; 12 (3): 165–168. doi: 10.4161/cbt.12.3.16292.

9. Navarro EB, López EV, Quijano Y et al. Impact of BRCA1/2 gene mutations on survival of patients with pancreatic cancer: a case-series analysis. Ann Hepatobiliary Pancreat Surg 2019; 23 (2): 200–205. doi: 10.14701/ahbps.2019.23.2.200.

10. Golan T, Hammel P, Reni M et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med 2019; 381 (4): 317–327. doi: 10.1056/nejmoa1903387.

11. Aldubayan SH, Pyle L, Gamulin M et al. Association of inherited pathogenic variants in checkpoint kinase 2 (CHEK2) with susceptibility to testicular germ cell tumors. JAMA Oncol 2019; 5 (4): 514–522. doi: 10.1001/jamaoncol.2018.6477.

12. Bartsch DK, Krysewski K, Sina-Frey M et al. Low frequency of CHEK2 mutations in familial pancreatic cancer. Fam Cancer 2006; 5 (4): 305–308. doi: 10.1007/s10689-006-7850-4.

13. Young EL, Thompson BA, Neklason DW et al. Pancreatic cancer as a sentinel for hereditary cancer predisposition. BMC Cancer 2018; 18 (1): 697. doi: 10.1186/s12885-018-4573-5.

14. Pilarski R. The role of BRCA testing in hereditary pancreatic and prostate cancer families. Am Soc Clin Oncol Educ Book 2019; 39: 79–86. doi: 10.1200/EDBK_238977.