Combined treatment for locally advanced BRCA1-associated pancreatic cancer: a case report

   Pancreatic cancer (PC) remains one of the most aggressive malignancies with poor prognosis, particularly in locally advanced and metastatic forms. Germline BRCA1/2 mutations, found in approximately 5 % of PC patients, are associated with increased sensitivity to platinum-based chemotherapy (CT) and PARP inhibitor therapy. This article presents a clinical case of successful combined treatment for locally advanced BRCA1-associated PC. The reported case demonstrates the efficacy of a comprehensive approach incorporating platinum-based CT, irreversible electroporation (IRE), pancreatic resection, stereotactic radiotherapy (RT), and PARP inhibitor targeted therapy in BRCA1-associated PC. The study highlights the crucial importance of molecular genetic testing at initial diagnosis for optimal treatment strategy selection. The findings confirm both the efficacy and safety of prolonged olaparib administration, warranting further investigation of this therapeutic approach in clinical trials.

1. Malignant Neoplasms in Russia in 2023 (Morbidity and Mortality) / ed. by A. D. Kaprin [et al.]. Moscow: P. A. Herzen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 2024. 276 p.: ill.

2. Klein AP. Genetic susceptibility to pancreatic cancer. Mol Carcinog. 2012; 51 (1): 14–24. DOI: 10.1002/mc.20759

3. Solomon S, Das S, Brand R, Whitcomb DC. Inherited pancreatic cancer syndromes. Cancer J. 2012; 18 (6): 485–91. DOI: 10.1097/PPO.0b013e318278c4a6

4. Stadler ZK, Salo-Mullen E, Patil SM, et al. Prevalence of BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and pancreatic cancer. Cancer. 2012; 118 (2): 493–9. DOI: 10.1002/cncr.26191

5. Lowery MA, Wong W, Jordan EJ. et al. Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms. J Natl Cancer Inst. 2018; 110 (10): 1067–74. DOI: 10.1093/jnci/djy024

6. Chartron E, Theillet C, Guiu S, Jacot W. Targeting homologous repair deficiency in breast and ovarian cancers: biological pathways, preclinical and clinical data. Crit Rev Oncol Hematol. 2019; 133: 58–73. DOI: 10.1016/j.critrevonc.2018.10.012

7. The Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst. 1999; 91 (15): 1310–6. DOI: 10.1093/jnci/91.15.1310

8. Iqbal J, Ragone A, Lubinski J, et al. The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer. 2012; 107 (12): 2005–9. DOI: 10.1038/bjc.2012.483

9. Brose MS, Rebbeck TR, Calzone KA, Stopfer JE, Nathanson KL, Weber BL. Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst. 2002; 94 (18): 1365–72. DOI: 10.1093/jnci/94.18.1365

10. National Cancer Institute. SEER Cancer Stat Facts: Pancreatic Cancer. 2024.

11. Friedenson B. BRCA1 and BRCA2 pathways and the risk of cancers other than breast or ovarian. MedGenMed. 2005; 7 (2): 60. PMID: 16369442.

12. Wallace AJ. New challenges for BRCA testing: a view from the diagnostic laboratory. Eur J Hum Genet. 2016; 24 (Suppl 1): S 10–8. DOI: 10.1038/ejhg.2016.94

13. Wattenberg MM, Asch D, Yu S. et al. Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB 2 mutation. Br J Cancer. 2020; 122 (3): 333–9. DOI: 10.1038/s41416-019-0582-7

14. Golan T, Kanji ZS, Epelbaum R. et al. Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers. Br J Cancer. 2014; 111 (6): 1132–8. DOI: 10.1038/bjc.2014.418

15. Reiss KA, Yu S, Judy R. et al. Retrospective survival analysis of patients with advanced pancreatic ductal adenocarcinoma and germline BRCA or PALB 2 mutations. JCO Precis Oncol. 2018; 2: 1–9. DOI: 10.1200/PO.17.00152

16. Yu S, Agarwal P, Mamtani R. et al. Retrospective survival analysis of patients with resected pancreatic ductal adenocarcinoma and a germline BRCA or PALB 2 mutation. JCO Precis Oncol. 2019; 3: 1–11. DOI: 10.1200/PO.18.0027

17. Golan T, Hammel P, Reni M. et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019; 381 (4): 317–27. DOI: 10.1056/NEJMoa1903387

18. Astakhov D. A., Panchenkov D. N., Ivanov Yu.V. et al. Irreversible electroporation in locally advanced pancreatic cancer. Annals of Surgical Hepatology. 2018; 23(2): 59–68.

19. Okusaka T. Treatment for postoperative recurrence of pancreatic cancer : a narrative review. Chin Clin Oncol. 2022; 11 (3): 19. DOI: 10.21037/cco-21-87