Clinical characteristics of patients with Breast and / or Ovarian Cancer with mutations in the BRCA1 and BRCA2 genes in Córdoba, Argentina
DOI:
https://doi.org/10.31053/1853.0605.v79.n3.34533Keywords:
genes brca1, genes brca2, breast neoplasms, ovarian neoplasmsAbstract
Introduction: Hereditary predisposition syndromes to cancer represent 5-10% of cancer cases, the most studied being HBOC produced by mutations in the BRCA1/2 genes. Objectives: To describe clinical, histopathological and PV characteristics in patients with HBOC in Córdoba, Argentina and compare it with those without BRCA1/2 mutations. Methods: Cross-sectional, correlational and observational analysis of patients from Córdoba. The ANOVA, Student's t test contingency tables and Fisher exact test were used the significance level was α = 0.05. Results: 155 women with BC, OC and BC/OC were studied. 40 BRCA1 / 2 mutations were identified. No differences were found in the age of diagnosis between patients with and without BRCA1/2 mutations. A significant association was found between VP in BRCA1/2 and the type of cancer (p = 0.003); all cases with BC/OC presented mutations in BRCA1/2. No significant association was found between mutated/non-mutated and personal history, family background, and ER-PR-HER2. 23.1% and 38.1% of BC cases were TN in individuals with VP in BRCA 1 and 2, respectively. The prevalence of mutations was 25.8% and the prevalence of novel PV was 10.0%. Conclusions: Patients with BC-VP BRCA1/2 are associated with ductal histology, and younger age of presentation with VP BRCA1. We did not find significant differences in the age at diagnosis of BC between patients with BRCA1 and BRCA2 mutations, a higher proportion of BC TN is observed than in the general population. In our sample, the prevalence of BRCA1/2 mutations among patients who meet criteria for HBOC is 25.8%, with 10% new pathogenic variant.
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References
Diez Gilbert, O. Síndrome de cáncer de mama-ovario hereditario y susceptibilidad genética al cáncer de mama: Aspectos moleculares. En: Alonso MA, Balmaña J, Benavides MM, Blanco I, Bruneti, J, García-Foncillas J, González E, González S, Graña B, Guillén C, Lastra E, Mayordomo JI, Pérez P, Robles L, Urioste M, editores. Cáncer Hereditario. Madrid: Sociedad Española de Oncología Médica (SEOM); 2011. p. 383-417.
Antoniou AC, Easton DF. Risk prediction models for familial breast cancer. Future Oncol. 2006 Apr;2(2):257-74. doi: 10.2217/14796694.2.2.257.
Paluch-Shimon S, Cardoso F, Sessa C, Balmana J, Cardoso MJ, Gilbert F, Senkus E; ESMO Guidelines Committee. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann Oncol. 2016 Sep;27(suppl 5):v103-v110. doi: 10.1093/annonc/mdw327. Erratum in: Ann Oncol. 2017 Jul 1;28(suppl_4):iv167-iv168.
Urbina-Jara LK, Rojas-Martinez A, Martinez-Ledesma E, Aguilar D, Villarreal-Garza C, Ortiz-Lopez R. Landscape of Germline Mutations in DNA Repair Genes for Breast Cancer in Latin America: Opportunities for PARP-Like Inhibitors and Immunotherapy. Genes (Basel). 2019 Oct 10;10(10):786. doi: 10.3390/genes10100786.
Copson ER, Maishman TC, Tapper WJ, Cutress RI, Greville-Heygate S, Altman DG, Eccles B, Gerty S, Durcan LT, Jones L, Evans DG, Thompson AM, Pharoah P, Easton DF, Dunning AM, Hanby A, Lakhani S, Eeles R, Gilbert FJ, Hamed H, Hodgson S, Simmonds P, Stanton L, Eccles DM. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. Lancet Oncol. 2018 Feb;19(2):169-180. doi: 10.1016/S1470-2045(17)30891-4.
Incorvaia L, Fanale D, Badalamenti G, Bono M, Calò V, Cancelliere D, Castiglia M, Fiorino A, Pivetti A, Barraco N, Cutaia S, Russo A, Bazan V. Hereditary Breast and Ovarian Cancer in Families from Southern Italy (Sicily)-Prevalence and Geographic Distribution of Pathogenic Variants in BRCA1/2 Genes. Cancers (Basel). 2020 May 5;12(5):1158. doi: 10.3390/cancers12051158.
Cock-Rada AM, Ossa CA, Garcia HI, Gomez LR. A multi-gene panel study in hereditary breast and ovarian cancer in Colombia. Fam Cancer. 2018 Jan;17(1):23-30. doi: 10.1007/s10689-017-0004-z..
da Costa E Silva Carvalho S, Cury NM, Brotto DB, de Araujo LF, Rosa RCA, Texeira LA, Plaça JR, Marques AA, Peronni KC, Ruy PC, Molfetta GA, Moriguti JC, Carraro DM, Palmero EI, Ashton-Prolla P, de Faria Ferraz VE, Silva WA Jr. Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: analysis of a 21 gene panel in the Brazilian population. BMC Med Genomics. 2020 Feb 10;13(1):21. doi: 10.1186/s12920-019-0652-y.
Cancer today. [Internet]. Lyon: International Agency for Research on Cancer; c2020 [citado 2021 Jul 30]. Dsiponible en: https://gco.iarc.fr/today/online-analysis-map?v=2018&mode=population&mode_population=continents&population=900&populations=900&key=asr&sex=2&cancer=20&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&nb_items=10&group_cancer=1&include_nmsc=1&include_nmsc_other=1&projection=natural-earth&color_palette=default&map_scale=quantile&map_nb_colors=5&continent=0&rotate=%255B10%252C0%255D.
Atchley DP, Albarracin CT, Lopez A, Valero V, Amos CI, Gonzalez-Angulo AM, Hortobagyi GN, Arun BK. Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer. J Clin Oncol. 2008 Sep 10;26(26):4282-8. doi: 10.1200/JCO.2008.16.6231.
Rakha EA, Reis-Filho JS, Ellis IO. Basal-like breast cancer: a critical review. J Clin Oncol. 2008 May 20;26(15):2568-81. doi: 10.1200/JCO.2007.13.1748.
Foulkes WD, Stefansson IM, Chappuis PO, Bégin LR, Goffin JR, Wong N, Trudel M, Akslen LA. Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst. 2003 Oct 1;95(19):1482-5. doi: 10.1093/jnci/djg050.
Lacroix M, Leclercq G. The "portrait" of hereditary breast cancer. Breast Cancer Res Treat. 2005 Feb;89(3):297-304. doi: 10.1007/s10549-004-2172-4.
Lakhani SR, Reis-Filho JS, Fulford L, Penault-Llorca F, van der Vijver M, Parry S, Bishop T, Benitez J, Rivas C, Bignon YJ, Chang-Claude J, Hamann U, Cornelisse CJ, Devilee P, Beckmann MW, Nestle-Krämling C, Daly PA, Haites N, Varley J, Lalloo F, Evans G, Maugard C, Meijers-Heijboer H, Klijn JG, Olah E, Gusterson BA, Pilotti S, Radice P, Scherneck S, Sobol H, Jacquemier J, Wagner T, Peto J, Stratton MR, McGuffog L, Easton DF; Breast Cancer Linkage Consortium. Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res. 2005 Jul 15;11(14):5175-80. doi: 10.1158/1078-0432.CCR-04-2424.
Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM, Roeb W, Agnew KJ, Stray SM, Wickramanayake A, Norquist B, Pennington KP, Garcia RL, King MC, Swisher EM. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18032-7. doi: 10.1073/pnas.1115052108.
Alsop K, Fereday S, Meldrum C, deFazio A, Emmanuel C, George J, Dobrovic A, Birrer MJ, Webb PM, Stewart C, Friedlander M, Fox S, Bowtell D, Mitchell G. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol. 2012 Jul 20;30(21):2654-63. doi: 10.1200/JCO.2011.39.8545. Epub 2012 Jun 18. Erratum in: J Clin Oncol. 2012 Nov 20;30(33):4180.
Solano AR, Aceto GM, Delettieres D, Veschi S, Neuman MI, Alonso E, Chialina S, Chacón RD, Renato MC, Podestá EJ. BRCA1 And BRCA2 analysis of Argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin. Springerplus. 2012 Sep 25;1:20. doi: 10.1186/2193-1801-1-20.
Solano AR, Cardoso FC, Romano V, Perazzo F, Bas C, Recondo G, Santillan FB, Gonzalez E, Abalo E, Viniegra M, Michel JD, Nuñez LM, Noblia CM, Mc Lean I, Canton ED, Chacon RD, Cortese G, Varela EB, Greco M, Barrientos ML, Avila SA, Vuotto HD, Lorusso A, Podesta EJ, Mando OG. Spectrum of BRCA1/2 variants in 940 patients from Argentina including novel, deleterious and recurrent germline mutations: impact on healthcare and clinical practice. Oncotarget. 2016 Jul 24;8(36):60487-60495. doi: 10.18632/oncotarget.10814.
Frey MK, Kopparam RV, Ni Zhou Z, Fields JC, Buskwofie A, Carlson AD, Caputo T, Holcomb K, Chapman-Davis E. Prevalence of nonfounder BRCA1/2 mutations in Ashkenazi Jewish patients presenting for genetic testing at a hereditary breast and ovarian cancer center. Cancer. 2019 Mar 1;125(5):690-697. doi: 10.1002/cncr.31856.
Núñez LM, Cólica V., Valdez R., Telias D. Schenone, G. Asesoramiento genético en oncología: manual para la práctica clínica. Buenos Aires: Instituto Nacional del Cáncer: Ministerio de Salud. Presidencia de la Nación; 2013.
Rebbeck TR, Friebel TM, Friedman E, Hamann U, Huo D, Kwong A, Olah E, Olopade OI, Solano AR, Teo SH, Thomassen M, Weitzel JN, Chan TL, Couch FJ, Goldgar DE, Kruse TA, Palmero EI, Park SK, Torres D, van Rensburg EJ, McGuffog L, Parsons MT, Leslie G, Aalfs CM, Abugattas J, Adlard J, Agata S, Aittomäki K, Andrews L, Andrulis IL, Arason A, Arnold N, Arun BK, Asseryanis E, Auerbach L, Azzollini J, Balmaña J, Barile M, Barkardottir RB, Barrowdale D, Benitez J, Berger A, Berger R, Blanco AM, Blazer KR, Blok MJ, Bonadona V, Bonanni B, Bradbury AR, Brewer C, Buecher B, Buys SS, Caldes T, Caliebe A, Caligo MA, Campbell I, Caputo SM, Chiquette J, Chung WK, Claes KBM, Collée JM, Cook J, Davidson R, de la Hoya M, De Leeneer K, de Pauw A, Delnatte C, Diez O, Ding YC, Ditsch N, Domchek SM, Dorfling CM, Velazquez C, Dworniczak B, Eason J, Easton DF, Eeles R, Ehrencrona H, Ejlertsen B; EMBRACE, Engel C, Engert S, Evans DG, Faivre L, Feliubadaló L, Ferrer SF, Foretova L, Fowler J, Frost D, Galvão HCR, Ganz PA, Garber J, Gauthier-Villars M, Gehrig A; GEMO Study Collaborators, Gerdes AM, Gesta P, Giannini G, Giraud S, Glendon G, Godwin AK, Greene MH, Gronwald J, Gutierrez-Barrera A, Hahnen E, Hauke J; HEBON, Henderson A, Hentschel J, Hogervorst FBL, Honisch E, Imyanitov EN, Isaacs C, Izatt L, Izquierdo A, Jakubowska A, James P, Janavicius R, Jensen UB, John EM, Vijai J, Kaczmarek K, Karlan BY, Kast K, Investigators K, Kim SW, Konstantopoulou I, Korach J, Laitman Y, Lasa A, Lasset C, Lázaro C, Lee A, Lee MH, Lester J, Lesueur F, Liljegren A, Lindor NM, Longy M, Loud JT, Lu KH, Lubinski J, Machackova E, Manoukian S, Mari V, Martínez-Bouzas C, Matrai Z, Mebirouk N, Meijers-Heijboer HEJ, Meindl A, Mensenkamp AR, Mickys U, Miller A, Montagna M, Moysich KB, Mulligan AM, Musinsky J, Neuhausen SL, Nevanlinna H, Ngeow J, Nguyen HP, Niederacher D, Nielsen HR, Nielsen FC, Nussbaum RL, Offit K, Öfverholm A, Ong KR, Osorio A, Papi L, Papp J, Pasini B, Pedersen IS, Peixoto A, Peruga N, Peterlongo P, Pohl E, Pradhan N, Prajzendanc K, Prieur F, Pujol P, Radice P, Ramus SJ, Rantala J, Rashid MU, Rhiem K, Robson M, Rodriguez GC, Rogers MT, Rudaitis V, Schmidt AY, Schmutzler RK, Senter L, Shah PD, Sharma P, Side LE, Simard J, Singer CF, Skytte AB, Slavin TP, Snape K, Sobol H, Southey M, Steele L, Steinemann D, Sukiennicki G, Sutter C, Szabo CI, Tan YY, Teixeira MR, Terry MB, Teulé A, Thomas A, Thull DL, Tischkowitz M, Tognazzo S, Toland AE, Topka S, Trainer AH, Tung N, van Asperen CJ, van der Hout AH, van der Kolk LE, van der Luijt RB, Van Heetvelde M, Varesco L, Varon-Mateeva R, Vega A, Villarreal-Garza C, von Wachenfeldt A, Walker L, Wang-Gohrke S, Wappenschmidt B, Weber BHF, Yannoukakos D, Yoon SY, Zanzottera C, Zidan J, Zorn KK, Hutten Selkirk CG, Hulick PJ, Chenevix-Trench G, Spurdle AB, Antoniou AC, Nathanson KL. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Hum Mutat. 2018 May;39(5):593-620. doi: 10.1002/humu.23406.
Muranen TA, Khan S, Fagerholm R, Aittomäki K, Cunningham JM, Dennis J, Leslie G, McGuffog L, Parsons MT, Simard J, Slager S, Soucy P, Easton DF, Tischkowitz M, Spurdle AB; kConFab Investigators, Schmutzler RK, Wappenschmidt B, Hahnen E, Hooning MJ; HEBON Investigators, Singer CF, Wagner G, Thomassen M, Pedersen IS, Domchek SM, Nathanson KL, Lazaro C, Rossing CM, Andrulis IL, Teixeira MR, James P, Garber J, Weitzel JN; SWE-BRCA Investigators, Jakubowska A, Yannoukakos D, John EM, Southey MC, Schmidt MK, Antoniou AC, Chenevix-Trench G, Blomqvist C, Nevanlinna H. Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer. NPJ Breast Cancer. 2020 Sep 10;6:44. doi: 10.1038/s41523-020-00185-6.
Santonocito C, Rizza R, Paris I, Marchis L, Paolillo C, Tiberi G, Scambia G, Capoluongo E. Spectrum of Germline BRCA1 and BRCA2 Variants Identified in 2351 Ovarian and Breast Cancer Patients Referring to a Reference Cancer Hospital of Rome. Cancers (Basel). 2020 May 19;12(5):1286. doi: 10.3390/cancers12051286.
Gallardo-Rincón D, Álvarez-Gómez RM, Montes-Servín E, Toledo-Leyva A, Montes-Servín E, Michel-Tello D, Alamilla-García G, Bahena-González A, Hernández-Nava E, Fragoso-Ontiveros V, Espinosa-Romero R, Cetina-Pérez L. Clinical Evaluation of BRCA1/2 Mutation in Mexican Ovarian Cancer Patients. Transl Oncol. 2020 Feb;13(2):212-220. doi: 10.1016/j.tranon.2019.11.003.
Solano AR, Liria NC, Jalil FS, Faggionato DM, Mele PG, Mampel A, Cardoso FC, Podesta EJ. BRCA1 and BRCA2 Mutations Other Than the Founder Alleles Among Ashkenazi Jewish in the Population of Argentina. Front Oncol. 2018 Aug 21;8:323. doi: 10.3389/fonc.2018.00323.
Zhu Y, Wu J, Zhang C, Sun S, Zhang J, Liu W, Huang J, Zhang Z. BRCA mutations and survival in breast cancer: an updated systematic review and meta-analysis. Oncotarget. 2016 Oct 25;7(43):70113-70127. doi: 10.18632/oncotarget.12158.
Ossa CA, Torres D. Founder and Recurrent Mutations in BRCA1 and BRCA2 Genes in Latin American Countries: State of the Art and Literature Review. Oncologist. 2016 Jul;21(7):832-9. doi: 10.1634/theoncologist.2015-0416.
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