medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2023-36-7-12medalphabet-3475Research ArticleСтатьиКлиническое значение герминальных мутаций в гене BRCA1/2 при протоковой аденокарциноме поджелудочной железы (обзор литературы)Clinical significance of germline mutations in BRCA1/2 gene in pancreatic ductal adenocarcinoma (literature review)https://orcid.org/0000-0002-5058-8821МоисеенкоВ. Е.MoiseenkoV. E.

Моисеенко Владислав Евгеньевич, к. м. н., врач-хирург, онколог отделения хирургии № 2.

Санкт-Петербург

Moiseenko Vladislav E. - PhD Med, surgeon, oncologist of Dept of Surgery No. 2.

Saint Petersburg

tmpr@inbox.ruhttps://orcid.org/0000-0003-3994-1329ПавловскийА. В.PavlovskiiA. V.

Павловский Александр Васильевич - д. м. н., г. н. с.

Санкт-Петербург

Pavlovsky Alexander V. - DM Sci (habil.), chief researcher.

Saint Petersburg

prof.pavlovskiy@mail.ruhttps://orcid.org/0000-0004-5158-8895ПоповС. А.PopovS. A.

Попов Сергей Александрович - к. м. н., врач-хирург, онколог отделения хирургии № 2.

Санкт-Петербург

Popov Sergey A. - PhD Med, surgeon, oncologist of Dept of Surgery No. 2.

Saint Petersburg

spsergey@inbox.ruhttps://orcid.org/0000-0002-8746-8452ГрановД. А.GranovD. A.

Гранов Дмитрий Анатольевич - д. м. н., проф., акад. РАН, научный руководитель.

Санкт-Петербург

Granov Dmitry A. - DM Sci (habil.), professor, academician of RAS, scientific director.

Saint Petersburg

d.granov@gmail.ruhttps://orcid.org/0000-0002-2207-767XТурлакА. С.TurlakA. S.

Турлак Анастасия Сергеевна - клинический ординатор кафедры радиологии, хирургии и онкологии.

Санкт-Петербург

Turlak Anastasia S. - clinical resident of Dept of Radiology, Surgery and Oncology.

Saint Petersburg

a_turlak18@mail.ruАванесянГ. Р.AvanesyanG. R.

Аванесян Гарри Рубенович - студент VI курса педиатрического факультета.

Санкт-Петербург

Avanesyan Garry R. - 6th year student of Faculty of Pediatrics.

Saint Petersburg

ФГБУ «Российский научный центр радиологии и хирургических технологий имени академика А.М. Гранова» Минздрава РоссииРоссияRussian Scientific Centre of Radiology and Surgical Technologies n. a. academician A.M. GranovRussian FederationФГБОУ ВО «Санкт-Петербургский государственный педиатрический университет» Минздрава РоссииРоссияSaint Petersburg State Pediatric Medical UniversityRussian Federation202317012024036Диагностика и терапия (4)712Copyright © Моисеенко В.Е., Павловский А.В., Попов С.А., Гранов Д.А., Турлак А.С., Аванесян Г.Р., 20242024Моисеенко В.Е., Павловский А.В., Попов С.А., Гранов Д.А., Турлак А.С., Аванесян Г.Р.Moiseenko V.E., Pavlovskii A.V., Popov S.A., Granov D.A., Turlak A.S., Avanesyan G.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/3475

Протоковая аденокарцинома поджелудочной железы занимает лидирующие позиции по смертности среди всех злокачественных новообразований. Пятилетняя выживаемость больных составляет менее 9 %. При мутации в гене BRCA риск возникновения опухоли повышается, однако влияние данной мутации на клиническое течение болезни мало изучено и представляет определенный научно-практический интерес. Представлен обзор мировой литературы о клиническом значении герминальных мутаций – рисках возникновения злокачественного новообразования, выборе тактики лечения.

Pancreatic ductal adenocarcinoma occupies a leading position in mortality among other malignant neoplasms. The five-year survival of patients is less than 9 %. Risk of a tumor development increases with a mutation in the BRCA gene, however, the effect of this mutation on the clinical course of the disease has been poorly studied and is of certain scientific and practical interest. A review of the world literature on the clinical significance of germline mutations – the risks of malignancy, the choice of treatment tactics – is presented.

герминальные мутациирак поджелудочной железыBRCA1/2germline mutationspancreatic cancerBRCA1/2ReferencesSiegel R. L., Miller K. D., Wagle N. S., Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023; 73 (1): 17–48. https://doi.org/10.3322/caac.21763Siegel R. L., Miller K. D., Wagle N. S., Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023; 73 (1): 17–48. https://doi.org/10.3322/caac.21763Моисеенко В. Е., Павловский А. В., Гранов Д. А., Карданова И. Г., Кочорова Л. В., Додонова И. В. Показатели заболеваемости злокачественными новообразованиями поджелудочной железы в Российской Федерации: ретроспективное когортное исследование. Кубанский научный медицинский вестник. 2021; 28 (3): 97–111. https://doi.org/10.25207/1608–6228–2021–28–3–97–111Moiseenko V. E., Pavlovsky A. V., Granov D. A., Kardanova I. G., Kochorova L. V., Dodonova I. V. Incidence rates of pancreatic malignancies in the Russian Federation: A retrospective cohort study. Kuban Scientific Medical Bulletin. 2021; 28 (3): 97–111. https://doi.org/10.25207/1608–6228–2021–28–3–97–111Каприн А. Д., Старинский В.В, Шахзодова А. О. Злокачественные новообразования в России в 2020 году (заболеваемость и смертность). М.: МНИОИ им. П. А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России. 2021; 252.Kaprin A. D., Starinsky V. V., Shakhzodova A. O. Malignant neoplasms in Russia in 2020 (morbidity and mortality). M.: Moscow Research Institute of Oncology n. a. P. A. Herzen – a Branch of the National Medical Research Centre of Radiology. 2021; 252.Моисеенко В. Е., Павловский А. В., Гранов Д. А., Кочорова Л. В., Додонов, И.В., Хижа В. В., Язенок А. В., Яковенко Т. В. Анализ статистических показателей населения СанктПетербурга, страдающих злокачественными новообразованиями поджелудочной железы. Вестник Российской Военно-медицинской академии. 2021; 23 (2): 155–164. https://doi.org/10.17816/brmma60343Moiseenko V. E., Pavlovsky A. V., Granov D. A., Kochorova L. V., Dodonov, I.V., Khizha V. V., Yazenok A. V., Yakovenko T. V. Analysis of statistical indicators of the population of St. Petersburg suffering from malignant neoplasms of the pancreas. Bulletin of the Russian Military Medical Academy. 2021; 23 (2): 155–164. https://doi.org/10.17816/brmma60343Моисеенко В. Е., Пономарев П. А., Павловский А. В., Гранов Д. А., Кочорова Л. В., Вишняков Н. И. Анализ клинических характеристик пациентов со злокачественными новообразованиями поджелудочной железы, получивших медицинскую помощь в стационарах Санкт-Петербурга в период с 2015 по 2020 год. Ученые записки Первого СанктПетербургского государственного медицинского университета имени академика И. П. Павлова. 2022; 29 (2): 16–23. https://doi.org/10.24884/1607–4181–2022–29–2–16–23Moiseenko V. E., Ponomarev P. A., Pavlovsky A. V., Granov D. A., Kochorova L. V., Vishnyakov N. I. Analysis of the clinical characteristics of patients with malignant neoplasms of the pancreas who received medical care in hospitals in St. Petersburg in the period from 2015 to 2020. Scientific notes of the First St. Petersburg State Medical University n. a. academician I. P. Pavlova. 2022; 29 (2): 16–23. https://doi.org/10.24884/1607–4181–2022–29–2–16–23Trikudanathan G., Lou E., Maitra A., Majumder S. Early detection of pancreatic cancer: Current state and future opportunities. Curr Opin Gastroenterol. 2021; 37 (5): 532–538. https://doi.org/10.1097/mog.0000000000000770Trikudanathan G., Lou E., Maitra A., Majumder S. Early detection of pancreatic cancer: Current state and future opportunities. Curr Opin Gastroenterol. 2021; 37 (5): 532–538. https://doi.org/10.1097/mog.0000000000000770Neoptolemos J. P., Palmer D. H., Ghaneh P., Psarelli E. E., Valle J. W., Hallora C. M., Faluyi O., O’Reilly D.A., Cunningham D., Wadsley J., Darby S., Meyer T., Gillmore R., Anthoney A., Lind P., Glimelius B., Falk S., Izbicki J. R., Middleton G. W., Büchler M. W. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): A multicentre, open-label, randomised, phase 3 trial. The Lancet. 2017; 389 (10073): 1011–1024. https://doi.org/10.1016/s0140–6736(16)32409–6Neoptolemos J. P., Palmer D. H., Ghaneh P., Psarelli E. E., Valle J. W., Hallora C. M., Faluyi O., O’Reilly D.A., Cunningham D., Wadsley J., Darby S., Meyer T., Gillmore R., Anthoney A., Lind P., Glimelius B., Falk S., Izbicki J. R., Middleton G. W., Büchler M. W. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): A multicentre, open-label, randomised, phase 3 trial. The Lancet. 2017; 389 (10073): 1011–1024. https://doi.org/10.1016/s0140–6736(16)32409–6Conroy T., Desseigne F., Ychou M., et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011; 364 (19): 1817–1825. https://doi.org/10.1056/nejmoa1011923Conroy T., Desseigne F., Ychou M., et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011; 364 (19): 1817–1825. https://doi.org/10.1056/nejmoa1011923Murphy K. M., Brune K. A., Griffin C. et al. Evaluation of candidate genes MAP2K4, MADH4, ACVR 1B, and BRCA2 in familial pancreatic cancer: Deleterious BRCA2 mutations in 17 %. Cancer Res. 2002; 62 (13): 3789–3793.Murphy K. M., Brune K. A., Griffin C. et al. Evaluation of candidate genes MAP2K4, MADH4, ACVR 1B, and BRCA2 in familial pancreatic cancer: Deleterious BRCA2 mutations in 17 %. Cancer Res. 2002; 62 (13): 3789–3793.Roberts N. J., Norris A. L., Petersen G. M. et al. Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer. Cancer Discov. 2016; 6 (2): 166–175. https://doi.org/10.1158/2159–8290.cd-15–0402Roberts N. J., Norris A. L., Petersen G. M. et al. Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer. Cancer Discov. 2016; 6 (2): 166–175. https://doi.org/10.1158/2159–8290.cd-15–0402Salo-Mullen E.E., O’Reilly E.M., Kelsen D. P., Ashraf A. M., Lowery M. A., Yu K. H., Reidy D. L., Epstein A. S., Lincoln A., Saldia A., Jacobs L. M., Rau-Murthy R., Zhang L. et al. Identification of germline genetic mutations in patients with pancreatic cancer. Cancer. 2015; 121: 4382–4388. https://doi.org/10.1002/cncr.29664Salo-Mullen E.E., O’Reilly E.M., Kelsen D. P., Ashraf A. M., Lowery M. A., Yu K. H., Reidy D. L., Epstein A. S., Lincoln A., Saldia A., Jacobs L. M., Rau-Murthy R., Zhang L. et al. Identification of germline genetic mutations in patients with pancreatic cancer. Cancer. 2015; 121: 4382–4388. https://doi.org/10.1002/cncr.29664Greer J. B., Lynch H. T., Brand R. E. Hereditary pancreatic cancer: A clinical perspective. Best Pract Res Clin Gastroenterol. 2009; 23: 159–70. https://doi.org/10.1016/j.bpg.2009.02.001Greer J. B., Lynch H. T., Brand R. E. Hereditary pancreatic cancer: A clinical perspective. Best Pract Res Clin Gastroenterol. 2009; 23: 159–70. https://doi.org/10.1016/j.bpg.2009.02.001Greer J. B., Whitcomb D. C., Brand R. E. Genetic predisposition to pancreatic cancer: A brief review. Am J Gastroenterol. 2007; 102: 2564–2569. https://doi.org/10.1111/j.1572–0241.2007.01475.xGreer J. B., Whitcomb D. C., Brand R. E. Genetic predisposition to pancreatic cancer: A brief review. Am J Gastroenterol. 2007; 102: 2564–2569. https://doi.org/10.1111/j.1572–0241.2007.01475.xZhen D. B., Rabe K. G., Gallinger S., Syngal S., Schwartz A. G., Goggins M. G., Hruban R. H., Cote M. L., McWilliams R.R., Roberts N. J., Cannon-Albright L.A., Li D., Moyes K., Wenstrup R. J., Hartman A. R., Seminara D., Klein A. P., Petersen G. M. BRCA1, BRCA2, PALB 2, and CDKN 2A mutations in familial pancreatic cancer: A PACGENE study. Genetics in Medicine. 2015; 17 (7): 569–577. https://doi.org/10.1038/gim.2014.153Zhen D. B., Rabe K. G., Gallinger S., Syngal S., Schwartz A. G., Goggins M. G., Hruban R. H., Cote M. L., McWilliams R.R., Roberts N. J., Cannon-Albright L.A., Li D., Moyes K., Wenstrup R. J., Hartman A. R., Seminara D., Klein A. P., Petersen G. M. BRCA1, BRCA2, PALB 2, and CDKN 2A mutations in familial pancreatic cancer: A PACGENE study. Genetics in Medicine. 2015; 17 (7): 569–577. https://doi.org/10.1038/gim.2014.153Møller P., Hagen A. I., Apold J., Maehle L., Clark N., Fiane B., Løvslett K., Hovig E., Vabø A. Genetic epidemiology of BRCA mutations – family history detects less than 50 % of the mutation carriers. Eur J Cancer. 2007; 43: 1713–1717. https://doi.org/10.1016/j.ejca.2007.04.023Møller P., Hagen A. I., Apold J., Maehle L., Clark N., Fiane B., Løvslett K., Hovig E., Vabø A. Genetic epidemiology of BRCA mutations – family history detects less than 50 % of the mutation carriers. Eur J Cancer. 2007; 43: 1713–1717. https://doi.org/10.1016/j.ejca.2007.04.023Holter S., Borgida A., Dodd A., Grant R., Semotiuk K., Hedley D., Dhani N., Narod S., Akbari M., Moore M., Gallinger S. Germline BRCA mutations in a large clinic-based cohort of patients with pancreatic adenocarcinoma. J Clin Oncol. 2015; 33: 3124–3129. https://doi.org/10.1200/jco.2014.59.7401Holter S., Borgida A., Dodd A., Grant R., Semotiuk K., Hedley D., Dhani N., Narod S., Akbari M., Moore M., Gallinger S. Germline BRCA mutations in a large clinic-based cohort of patients with pancreatic adenocarcinoma. J Clin Oncol. 2015; 33: 3124–3129. https://doi.org/10.1200/jco.2014.59.7401Shindo K., Yu J., Suenaga M., Fesharakizadeh S., Cho C., Macgregor-Das A., Siddiqui A., Witmer P. D., Tamura K., Song T. J., Navarro Almario J. A., Brant A., Borges M., Ford M., Barkley T., He J., Weiss M. J., Wolfgang C. L., Roberts N. J., Hruban R. H., Klein A. P., Goggins M. Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma. J Clin Oncol. 2017; 35: 3382–3390. https://doi.org/10.1200/jco.2017.72.3502Shindo K., Yu J., Suenaga M., Fesharakizadeh S., Cho C., Macgregor-Das A., Siddiqui A., Witmer P. D., Tamura K., Song T. J., Navarro Almario J. A., Brant A., Borges M., Ford M., Barkley T., He J., Weiss M. J., Wolfgang C. L., Roberts N. J., Hruban R. H., Klein A. P., Goggins M. Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma. J Clin Oncol. 2017; 35: 3382–3390. https://doi.org/10.1200/jco.2017.72.3502Kondo T., Kanai M., Kou T., Sakuma T., Mochizuki H., Kamada M., Nakatsui M., Uza N., Kodama Y., Masui T., Takaori K., Matsumoto S., Miyake H., Okuno Y., Muto M. Association between homologous recombination repair gene mutations and response to oxaliplatin in pancreatic cancer. Oncotarget. 2018; 9: 19817–19825. https://doi.org/10.18632/oncotarget.24865Kondo T., Kanai M., Kou T., Sakuma T., Mochizuki H., Kamada M., Nakatsui M., Uza N., Kodama Y., Masui T., Takaori K., Matsumoto S., Miyake H., Okuno Y., Muto M. Association between homologous recombination repair gene mutations and response to oxaliplatin in pancreatic cancer. Oncotarget. 2018; 9: 19817–19825. https://doi.org/10.18632/oncotarget.24865Gabai-Kapara E., Lahad A., Kaufman B., Friedman E., Segev S., Renbaum P., Beeri R., Gal M., Grinshpun-Cohen J., Djemal K., Mandell J. B., Lee M. K., Beller U., Catane R., King M. C., Levy-Lahad E. Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2. Proc Natl Acad Sci USA. 2014; 111: 14205–14210. https://doi.org/10.1073/pnas.1415979111Gabai-Kapara E., Lahad A., Kaufman B., Friedman E., Segev S., Renbaum P., Beeri R., Gal M., Grinshpun-Cohen J., Djemal K., Mandell J. B., Lee M. K., Beller U., Catane R., King M. C., Levy-Lahad E. Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2. Proc Natl Acad Sci USA. 2014; 111: 14205–14210. https://doi.org/10.1073/pnas.1415979111Manchanda R., Loggenberg K., Sanderson S., Burnell M., Wardle J., Gessler S., Side L., Balogun N., Desai R., Kumar A., Dorkins H., Wallis Y., Chapman C., Taylor R., Jacobs C., Tomlinson I., McGuire A., Beller U., Menon U., Jacobs I. Population testing for cancer predisposing BRCA1/BRCA2 mutations in the Ashkenazi-Jewish community: A randomized controlled trial. J Natl Cancer Inst. 2015; 107: 379–390. https://doi.org/10.1093/jnci/dju379Manchanda R., Loggenberg K., Sanderson S., Burnell M., Wardle J., Gessler S., Side L., Balogun N., Desai R., Kumar A., Dorkins H., Wallis Y., Chapman C., Taylor R., Jacobs C., Tomlinson I., McGuire A., Beller U., Menon U., Jacobs I. Population testing for cancer predisposing BRCA1/BRCA2 mutations in the Ashkenazi-Jewish community: A randomized controlled trial. J Natl Cancer Inst. 2015; 107: 379–390. https://doi.org/10.1093/jnci/dju379Metcalfe K. A., Poll A., Royer R., Llacuachaqui M., Tulman A., Sun P., Narod S. A. Screening for founder mutations in BRCA1 and BRCA2 in unselected Jewish women. J Clin Oncol. 2010; 28: 387–391. https://doi.org/10.1200/jco.2009.25.0712Metcalfe K. A., Poll A., Royer R., Llacuachaqui M., Tulman A., Sun P., Narod S. A. Screening for founder mutations in BRCA1 and BRCA2 in unselected Jewish women. J Clin Oncol. 2010; 28: 387–391. https://doi.org/10.1200/jco.2009.25.0712Tennen R. I., Laskey S. B., Koelsch B. L., McIntyre M.H., Tung J. Y. Identifying Ashkenazi jewish BRCA1/2 founder variants in individuals who do not self-report Jewish ancestry. Sci Rep. 2020; 10: 7669. https://doi.org/10.1038/s41598–020–63466-xTennen R. I., Laskey S. B., Koelsch B. L., McIntyre M.H., Tung J. Y. Identifying Ashkenazi jewish BRCA1/2 founder variants in individuals who do not self-report Jewish ancestry. Sci Rep. 2020; 10: 7669. https://doi.org/10.1038/s41598–020–63466-xMandelker D., Zhang L., Kemel Y., Stadler Z. K., Joseph V., Zehir A., Pradhan N., Arnold A., Walsh M. F., Li Y., Balakrishnan A. R., Syed A., Prasad M., Nafa K., Carlo M. I., Cadoo K. A., Sheehan M., Fleischut M. H., Salo-Mullen E., Trottier M., Lipkin S. M., Lincoln A., Mukherjee S., Ravichandran V., Cambria R., Galle J., Abida W., Arcila M. E., Benayed R., Shah R., Yu K., Bajorin D. F., Coleman J. A., Leach S. D., Lowery M. A., Garcia-Aguilar J., Kantoff P. W., Sawyers C. L., Dickler M. N., Saltz L., Motzer R. J., O’Reilly E.M., Scher H. I., Baselga J., Klimstra D. S., Solit D. B., Hyman D. M., Berger M. F., Ladanyi M., Robson M. E., Offit K. Mutation detection in patients with advanced cancer by universal sequencing of cancer-related genes in tumor and normal DNA vs guideline-based germline testing. JAMA. 2017; 318: 825–835. https://doi.org/10.1001/jama.2017.11137Mandelker D., Zhang L., Kemel Y., Stadler Z. K., Joseph V., Zehir A., Pradhan N., Arnold A., Walsh M. F., Li Y., Balakrishnan A. R., Syed A., Prasad M., Nafa K., Carlo M. I., Cadoo K. A., Sheehan M., Fleischut M. H., Salo-Mullen E., Trottier M., Lipkin S. M., Lincoln A., Mukherjee S., Ravichandran V., Cambria R., Galle J., Abida W., Arcila M. E., Benayed R., Shah R., Yu K., Bajorin D. F., Coleman J. A., Leach S. D., Lowery M. A., Garcia-Aguilar J., Kantoff P. W., Sawyers C. L., Dickler M. N., Saltz L., Motzer R. J., O’Reilly E.M., Scher H. I., Baselga J., Klimstra D. S., Solit D. B., Hyman D. M., Berger M. F., Ladanyi M., Robson M. E., Offit K. Mutation detection in patients with advanced cancer by universal sequencing of cancer-related genes in tumor and normal DNA vs guideline-based germline testing. JAMA. 2017; 318: 825–835. https://doi.org/10.1001/jama.2017.11137Daly M. B., Pilarski R., Yurgelun M. B., Berry M. P., Buys S. S., Dickson P., Domchek S. M., Elkhanany A., Friedman S., Garber J. E., Goggins M., Hutton M. L., Khan S., Klein C., Kohlmann W., Kurian A. W., Laronga C., Litton J. K., Mak J. S., Menendez C. S., Merajver S. D., Norquist B. S., Offit K., Pal T., Pederson H. J., Reiser G., Shannon K. M., Visvanathan K., Weitzel J. N., Wick M. J., Wisinski K. B., Dwyer M. A., Darlow S. D. NCCN Guidelines. Genetic/familial highrisk assessment: Breast, ovarian, and pancreatic version 1.2020. J Natl Compr Cancer Netw. 2020; 18: 380–391. https://doi.org/10.6004/jnccn.2020.0017Daly M. B., Pilarski R., Yurgelun M. B., Berry M. P., Buys S. S., Dickson P., Domchek S. M., Elkhanany A., Friedman S., Garber J. E., Goggins M., Hutton M. L., Khan S., Klein C., Kohlmann W., Kurian A. W., Laronga C., Litton J. K., Mak J. S., Menendez C. S., Merajver S. D., Norquist B. S., Offit K., Pal T., Pederson H. J., Reiser G., Shannon K. M., Visvanathan K., Weitzel J. N., Wick M. J., Wisinski K. B., Dwyer M. A., Darlow S. D. NCCN Guidelines. Genetic/familial highrisk assessment: Breast, ovarian, and pancreatic version 1.2020. J Natl Compr Cancer Netw. 2020; 18: 380–391. https://doi.org/10.6004/jnccn.2020.0017Zhen D. B., Rabe K. G., Gallinger S., Syngal S., Schwartz A. G., Goggins M. G., Hruban R. H., Cote M. L., McWilliams R.R., Roberts N. J., Cannon-Albright L.A., Li D., Moyes K., Wenstrup R. J., Hartman A. R., Seminara D., Klein A. P., Petersen G. M. BRCA1, BRCA2, PALB 2 and CDKN 2A mutations in familial pancreatic cancer: A PACGENE study. Genet Med. 2015; 17: 569–577. https://doi.org/10.1038/gim.2014.153Zhen D. B., Rabe K. G., Gallinger S., Syngal S., Schwartz A. G., Goggins M. G., Hruban R. H., Cote M. L., McWilliams R.R., Roberts N. J., Cannon-Albright L.A., Li D., Moyes K., Wenstrup R. J., Hartman A. R., Seminara D., Klein A. P., Petersen G. M. BRCA1, BRCA2, PALB 2 and CDKN 2A mutations in familial pancreatic cancer: A PACGENE study. Genet Med. 2015; 17: 569–577. https://doi.org/10.1038/gim.2014.153Smith A. L., Wong C., Cuggia A., Borgida A., Holter S., Hall A., Connor A. A., Bascuñana C., Asselah J., Bouganim N., Poulin V., Jolivet J., Vafiadis P., Le P., Martel G., Lemay F., Beaudoin A., Rafatzand K., Chaudhury P., Barkun J., Metrakos P., Marcus V., Omeroglu A., Chong G., Akbari M. R., Foulkes W. D., Gallinger S., Zogopoulos G. Reflex testing for germline BRCA1, BRCA2, PALB 2 and ATM mutations in pancreatic cancer: Mutation prevalence and clinical outcomes from two canadian research registries. JCO Precision Oncology. 2018; 2: 1–16. https://doi.org/10.1200/po.17.00098Smith A. L., Wong C., Cuggia A., Borgida A., Holter S., Hall A., Connor A. A., Bascuñana C., Asselah J., Bouganim N., Poulin V., Jolivet J., Vafiadis P., Le P., Martel G., Lemay F., Beaudoin A., Rafatzand K., Chaudhury P., Barkun J., Metrakos P., Marcus V., Omeroglu A., Chong G., Akbari M. R., Foulkes W. D., Gallinger S., Zogopoulos G. Reflex testing for germline BRCA1, BRCA2, PALB 2 and ATM mutations in pancreatic cancer: Mutation prevalence and clinical outcomes from two canadian research registries. JCO Precision Oncology. 2018; 2: 1–16. https://doi.org/10.1200/po.17.00098Ferrone C. R., Levine D. A., Tang L. H., Allen P. J., Jarnagin W., Brennan M. F., Offit K., Robson M. E. BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. J Clin Oncol. 2009; 27: 433–438. https://doi.org/10.1200/jco.2008.18.5546Ferrone C. R., Levine D. A., Tang L. H., Allen P. J., Jarnagin W., Brennan M. F., Offit K., Robson M. E. BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. J Clin Oncol. 2009; 27: 433–438. https://doi.org/10.1200/jco.2008.18.5546Golan T., Kanji Z. S., Epelbaum R., Devaud N., Dagan E., Holter S., Aderka D., Paluch-Shimon S., Kaufman B., Gershoni-Baruch R., Hedley D., Moore M. J., Friedman E., Gallinger S. Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers. Br J Cancer. 2014; 111: 1132–1138. https://doi.org/10.1038/bjc.2014.418Golan T., Kanji Z. S., Epelbaum R., Devaud N., Dagan E., Holter S., Aderka D., Paluch-Shimon S., Kaufman B., Gershoni-Baruch R., Hedley D., Moore M. J., Friedman E., Gallinger S. Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers. Br J Cancer. 2014; 111: 1132–1138. https://doi.org/10.1038/bjc.2014.418Golan T., Sella T., O’Reilly E.M., Katz M. H., Epelbaum R., Kelsen D. P., Borgida A., Maynard H., Kindler H., Friedmen E., Javle M., Gallinger S. Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer. Br J Cancer. 2017; 116: 697–702. https://doi.org/10.1038/bjc.2017.19Golan T., Sella T., O’Reilly E.M., Katz M. H., Epelbaum R., Kelsen D. P., Borgida A., Maynard H., Kindler H., Friedmen E., Javle M., Gallinger S. Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer. Br J Cancer. 2017; 116: 697–702. https://doi.org/10.1038/bjc.2017.19Pishvaian M. J., Blais E. M., Brody J. R., Lyons E., DeArbeloa P., Hendifar A., Mikhail S., Chung V., Sahai V., Sohal D. P.S., Bellakbira S., Thach D., Rahib L., Madhavan S., Matrisian L. M., Petricoin E. F. 3rd. Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: A retrospective analysis of the Know Your Tumor registry trial. Lancet Oncol 2020; 21: 508–518 https://doi.org/10.1016/s1470–2045(20)30074–7Pishvaian M. J., Blais E. M., Brody J. R., Lyons E., DeArbeloa P., Hendifar A., Mikhail S., Chung V., Sahai V., Sohal D. P.S., Bellakbira S., Thach D., Rahib L., Madhavan S., Matrisian L. M., Petricoin E. F. 3rd. Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: A retrospective analysis of the Know Your Tumor registry trial. Lancet Oncol 2020; 21: 508–518 https://doi.org/10.1016/s1470–2045(20)30074–7Perri G., Prakash L., Qiao W., Varadhachary G. R., Wolff R., Fogelman D., Overman M., Pant S., Javle M., Koay E. J., Herman J., Kim M., Ikoma N., Tzeng C. W., Lee J. E., Katz M. H.G. Response and survival associated with first-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel chemotherapy for localized pancreatic ductal adenocarcinoma. JAMA Surg 2020; 155: 832–839 https://doi.org/10.1001/jamasurg.2020.2286Perri G., Prakash L., Qiao W., Varadhachary G. R., Wolff R., Fogelman D., Overman M., Pant S., Javle M., Koay E. J., Herman J., Kim M., Ikoma N., Tzeng C. W., Lee J. E., Katz M. H.G. Response and survival associated with first-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel chemotherapy for localized pancreatic ductal adenocarcinoma. JAMA Surg 2020; 155: 832–839 https://doi.org/10.1001/jamasurg.2020.2286Williet N., Saint A., Pointet A. L., Tougeron D., Pernot S., Pozet A., Bechade D., Trouilloud I., Lourenco N., Hautefeuille V., Locher C., Desrame J., Artru P., Thirot Bidault A., Le Roy B., Pezet D., Phelip J. M., Taieb J. Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: A comparative propensity score study. Therapeutic Advances in Gastroenterology. 2019; 12: 1756284819878660 https://doi.org/10.1177/1756284819878660Williet N., Saint A., Pointet A. L., Tougeron D., Pernot S., Pozet A., Bechade D., Trouilloud I., Lourenco N., Hautefeuille V., Locher C., Desrame J., Artru P., Thirot Bidault A., Le Roy B., Pezet D., Phelip J. M., Taieb J. Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: A comparative propensity score study. Therapeutic Advances in Gastroenterology. 2019; 12: 1756284819878660 https://doi.org/10.1177/1756284819878660Bhattacharyya A., Ear U. S., Koller B. H., Weichselbaum R. R., Bishop D. K. The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. Journal of Biological Chemistry. 2000; 275: 23899–23903 https://doi.org/10.1074/jbc.c000276200Bhattacharyya A., Ear U. S., Koller B. H., Weichselbaum R. R., Bishop D. K. The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. Journal of Biological Chemistry. 2000; 275: 23899–23903 https://doi.org/10.1074/jbc.c000276200Mylavarapu S., Das A., Roy M. Role of BRCA mutations in the modulation of response to platinum therapy. Frontiers in Oncology. 2018; 8: 16 https://doi.org/10.3389/fonc.2018.00016Mylavarapu S., Das A., Roy M. Role of BRCA mutations in the modulation of response to platinum therapy. Frontiers in Oncology. 2018; 8: 16 https://doi.org/10.3389/fonc.2018.00016Golan T., Kanji Z. S., Epelbaum R., Devaud N., Dagan E., Holter S., Aderka D., Paluch-Shimon S., Kaufman B., Gershoni-Baruch R., Hedley D., Moore M. J., Friedman E., Gallinger S. Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers. Br J Cancer. 2014; 111: 1132–1138 https://doi.org/10.1038/bjc.2014.418Golan T., Kanji Z. S., Epelbaum R., Devaud N., Dagan E., Holter S., Aderka D., Paluch-Shimon S., Kaufman B., Gershoni-Baruch R., Hedley D., Moore M. J., Friedman E., Gallinger S. Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers. Br J Cancer. 2014; 111: 1132–1138 https://doi.org/10.1038/bjc.2014.418Blair A. B., Groot V. P., Gemenetzis G., Wei J., Cameron J. L., Weiss M. J., Goggins M., Wolfgang C. L., Yu J., He J. BRCA1/BRCA2 germline mutation carriers and sporadic pancreatic ductal adenocarcinoma. Journal of the American College of Surgeons. 2018; 226: 630–637. https://doi.org/10.1016/j.jamcollsurg.2017.12.021Blair A. B., Groot V. P., Gemenetzis G., Wei J., Cameron J. L., Weiss M. J., Goggins M., Wolfgang C. L., Yu J., He J. BRCA1/BRCA2 germline mutation carriers and sporadic pancreatic ductal adenocarcinoma. Journal of the American College of Surgeons. 2018; 226: 630–637. https://doi.org/10.1016/j.jamcollsurg.2017.12.021Reiss K. A., Yu S., Judy R., Symecko H., Nathanson K. L., Domchek S. M. Retrospective survival analysis of patients with advanced pancreatic ductal adenocarcinoma and germline BRCA or PALB 2 mutations. JCO PrecisOncol. 2018; 2: 1–9 https://doi.org/10.1200/po.17.00152Reiss K. A., Yu S., Judy R., Symecko H., Nathanson K. L., Domchek S. M. Retrospective survival analysis of patients with advanced pancreatic ductal adenocarcinoma and germline BRCA or PALB 2 mutations. JCO PrecisOncol. 2018; 2: 1–9 https://doi.org/10.1200/po.17.00152Yu S., Agarwal P., Mamtani R., Symecko H., Spielman K., O’Hara M., O’Dwyer P.J., Schneider C., Teitelbaum U., Nathanson K. L., Domchek S. M., Reiss K. A. Retrospective survival analysis of patients with resected pancreatic ductal adenocarcinoma and a germline BRCA or PALB 2 mutation. JCO Precis Oncol 2019; 2: 1–11 https://doi.org/10.1200/po.18.00271Yu S., Agarwal P., Mamtani R., Symecko H., Spielman K., O’Hara M., O’Dwyer P.J., Schneider C., Teitelbaum U., Nathanson K. L., Domchek S. M., Reiss K. A. Retrospective survival analysis of patients with resected pancreatic ductal adenocarcinoma and a germline BRCA or PALB 2 mutation. JCO Precis Oncol 2019; 2: 1–11 https://doi.org/10.1200/po.18.00271Farmer H., McCabe N., Lord C. J., Tutt A. N., Johnson D. A., Richardson T. B., Santarosa M., Dillon K. J., Hickson I., Knights C., Martin N. M., Jackson S. P., Smith G. C., Ashworth A. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005; 434: 917–92. https://doi.org/10.1038/nature03445Farmer H., McCabe N., Lord C. J., Tutt A. N., Johnson D. A., Richardson T. B., Santarosa M., Dillon K. J., Hickson I., Knights C., Martin N. M., Jackson S. P., Smith G. C., Ashworth A. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005; 434: 917–92. https://doi.org/10.1038/nature03445Mirza M. R., Coleman R. L., González-Martín A., Moore K. N., Colombo N., Ray-Coquard I., Pignata S. The forefront of ovarian cancer therapy: Update on PARP inhibitors. Ann Oncol. 2020; 31: 1148–1159 https://doi.org/10.1016/j.annonc.2020.06.004Mirza M. R., Coleman R. L., González-Martín A., Moore K. N., Colombo N., Ray-Coquard I., Pignata S. The forefront of ovarian cancer therapy: Update on PARP inhibitors. Ann Oncol. 2020; 31: 1148–1159 https://doi.org/10.1016/j.annonc.2020.06.004Mirza M. R., Monk B. J., Herrstedt J., Oza A. M., Mahner S., Redondo A., Fabbro M., Ledermann J. A., Lorusso D., Vergote I., Ben-Baruch N.E., Marth C., Mądry R., Christensen R. D., Berek J. S., Dørum A., Tinker A. V., du Bois A., González-Martín A., Follana P., Benigno B., Rosenberg P., Gilbert L., Rimel B. J., Buscema J., Balser J. P., Agarwal S., Matulonis U. A. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. New England Journal of Medicine. 2016; 375: 2154–2164 https://doi.org/10.1056/nejmoa1611310Mirza M. R., Monk B. J., Herrstedt J., Oza A. M., Mahner S., Redondo A., Fabbro M., Ledermann J. A., Lorusso D., Vergote I., Ben-Baruch N.E., Marth C., Mądry R., Christensen R. D., Berek J. S., Dørum A., Tinker A. V., du Bois A., González-Martín A., Follana P., Benigno B., Rosenberg P., Gilbert L., Rimel B. J., Buscema J., Balser J. P., Agarwal S., Matulonis U. A. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. New England Journal of Medicine. 2016; 375: 2154–2164 https://doi.org/10.1056/nejmoa1611310Litton J. K., Rugo H. S., Ettl J., Hurvitz S. A., Gonçalves A., Lee K. H., Fehrenbacher L., Yerushalmi R., Mina L. A., Martin M., Roché H., Im Y. H., Quek R. G.W., Markova D., Tudor I. C., Hannah A. L., Eiermann W., Blum J. L. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med 2018; 379: 753–763 https://doi.org/10.1056/nejmoa1802905Litton J. K., Rugo H. S., Ettl J., Hurvitz S. A., Gonçalves A., Lee K. H., Fehrenbacher L., Yerushalmi R., Mina L. A., Martin M., Roché H., Im Y. H., Quek R. G.W., Markova D., Tudor I. C., Hannah A. L., Eiermann W., Blum J. L. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med 2018; 379: 753–763 https://doi.org/10.1056/nejmoa1802905O’Reilly E.M., Lee J. W., Zalupski M., Capanu M., Park J., Golan T., Tahover E., Lowery M. A., Chou J. F., Sahai V., Brenner R., Kindler H. L., Yu K. H., Zervoudakis A., Vemuri S., Stadler Z. K., Do R. K.G., Dhani N., Chen A. P., Kelsen D. P. Randomized, multicenter, phase II trial of gemcitabine and cisplatin with or without veliparib in patients with pancreas adenocarcinoma and a germline BRCA/PALB 2 mutation. J Clin Oncol. 2020; 38: 1378–1388. PMID: 31976786 DOI: 10.1200/JCO.19.02931.O’Reilly E.M., Lee J. W., Zalupski M., Capanu M., Park J., Golan T., Tahover E., Lowery M. A., Chou J. F., Sahai V., Brenner R., Kindler H. L., Yu K. H., Zervoudakis A., Vemuri S., Stadler Z. K., Do R. K.G., Dhani N., Chen A. P., Kelsen D. P. Randomized, multicenter, phase II trial of gemcitabine and cisplatin with or without veliparib in patients with pancreas adenocarcinoma and a germline BRCA/PALB 2 mutation. J Clin Oncol. 2020; 38: 1378–1388. PMID: 31976786 DOI: 10.1200/JCO.19.02931.Lowery M. A., Kelsen D. P., Capanu M., Smith S. C., Lee J. W., Stadler Z. K., Moore M. J., Kindler H. L., Golan T., Segal A., Maynard H., Hollywood E., Moynahan M., Salo-Mullen E.E., Do R. K.G., Chen A. P., Yu K. H., Tang L. H., O’Reilly E. M. Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma. Eur J Cancer. 2018; 89: 19–26. https://doi.org/10.1016/j.ejca.2017.11.004Lowery M. A., Kelsen D. P., Capanu M., Smith S. C., Lee J. W., Stadler Z. K., Moore M. J., Kindler H. L., Golan T., Segal A., Maynard H., Hollywood E., Moynahan M., Salo-Mullen E.E., Do R. K.G., Chen A. P., Yu K. H., Tang L. H., O’Reilly E. M. Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma. Eur J Cancer. 2018; 89: 19–26. https://doi.org/10.1016/j.ejca.2017.11.004Kaufman B., Shapira-Frommer R., Schmutzler R. K., Audeh M. W., Friedlander M., Balmaña J., Mitchell G., Fried G., Stemmer S. M., Hubert A., Rosengarten O., Steiner M., Loman N., Bowen K., Fielding A., Domchek S. M. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 2015; 33: 244–250. https://doi.org/10.1200/jco.2014.56.2728Kaufman B., Shapira-Frommer R., Schmutzler R. K., Audeh M. W., Friedlander M., Balmaña J., Mitchell G., Fried G., Stemmer S. M., Hubert A., Rosengarten O., Steiner M., Loman N., Bowen K., Fielding A., Domchek S. M. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 2015; 33: 244–250. https://doi.org/10.1200/jco.2014.56.2728Golan T., Hammel P., Reni M., Van Cutsem E., Macarulla T., Hall M. J., Park J. O., Hochhauser D., Arnold D., Oh D. Y., Reinacher-Schick A., Tortora G., Algül H., O’Reilly E.M., McGuinness D., Cui K. Y., Schlienger K., Locker G. Y., Kindler H. L. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019; 381: 317–327. https://doi.org/10.1056/nejmoa1903387Golan T., Hammel P., Reni M., Van Cutsem E., Macarulla T., Hall M. J., Park J. O., Hochhauser D., Arnold D., Oh D. Y., Reinacher-Schick A., Tortora G., Algül H., O’Reilly E.M., McGuinness D., Cui K. Y., Schlienger K., Locker G. Y., Kindler H. L. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019; 381: 317–327. https://doi.org/10.1056/nejmoa1903387Waddell N., Pajic M., Patch A. M., Chang D. K., Kassahn K. S., Bailey P., Johns A. L., Miller D., Nones K., Quek K., Quinn M. C., Robertson A. J., Fadlullah M. Z., Bruxner T. J., Christ A. N., Harliwong I., Idrisoglu S., Manning S., Nourse C., Nourbakhsh E., Wani S., Wilson P. J., Markham E., et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 2015; 518: 495–501 https://doi.org/10.1371/journal.pone.0074380Waddell N., Pajic M., Patch A. M., Chang D. K., Kassahn K. S., Bailey P., Johns A. L., Miller D., Nones K., Quek K., Quinn M. C., Robertson A. J., Fadlullah M. Z., Bruxner T. J., Christ A. N., Harliwong I., Idrisoglu S., Manning S., Nourse C., Nourbakhsh E., Wani S., Wilson P. J., Markham E., et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 2015; 518: 495–501 https://doi.org/10.1371/journal.pone.0074380Sato H., Niimi A., Yasuhara T., Permata T. B.M., Hagiwara Y., Isono M., Nuryadi E., Sekine R., Oike T., Kakoti S., Yoshimoto Y., Held K. D., Suzuki Y., Kono K, Miyagawa K., Nakano T., Shibata A. DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells. Nat Commun 2017; 8: 175. htps://doi.org/10.1038/s41467–017–01883–9Sato H., Niimi A., Yasuhara T., Permata T. B.M., Hagiwara Y., Isono M., Nuryadi E., Sekine R., Oike T., Kakoti S., Yoshimoto Y., Held K. D., Suzuki Y., Kono K, Miyagawa K., Nakano T., Shibata A. DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells. Nat Commun 2017; 8: 175. htps://doi.org/10.1038/s41467–017–01883–9Seeber A., Zimmer K., Kocher F., Puccini A., Xiu J., Nabhan C., Elliott A., Goldberg R. M., Grothey A., Shields A. F., Battaglin F., El-Deiry W.S., Philip P. A., Marshall J. L., Hall M., Korn W. M., Lenz H. J., Wolf D., Feistritzer C., Spizzo G. Molecular characteristics of BRCA1/2 and PALB 2 mutations in pancreatic ductal adenocarcinoma. ESMO Open. 2020; 5: e000942. PMID: 33229504. https://doi.org/10.1136/esmoopen-2020–000942Seeber A., Zimmer K., Kocher F., Puccini A., Xiu J., Nabhan C., Elliott A., Goldberg R. M., Grothey A., Shields A. F., Battaglin F., El-Deiry W.S., Philip P. A., Marshall J. L., Hall M., Korn W. M., Lenz H. J., Wolf D., Feistritzer C., Spizzo G. Molecular characteristics of BRCA1/2 and PALB 2 mutations in pancreatic ductal adenocarcinoma. ESMO Open. 2020; 5: e000942. PMID: 33229504. https://doi.org/10.1136/esmoopen-2020–000942Vikas P., Borcherding N., Chennamadhavuni A., Garje R. Therapeutic potential of combining PARP inhibitor and immunotherapy in solid tumors. Front Oncol. 2020; 10: 570. https://doi.org/10.3389/fonc.2020.00570Vikas P., Borcherding N., Chennamadhavuni A., Garje R. Therapeutic potential of combining PARP inhibitor and immunotherapy in solid tumors. Front Oncol. 2020; 10: 570. https://doi.org/10.3389/fonc.2020.00570

The authors declare that there are no conflicts of interest present.