Panorama brasileiro e mundial da predisposição genética para a Síndrome do Câncer Hereditário de Mama e Ovário: uma revisão sistemática: Brazilian and global overview of genetic predisposition for Hereditary Breast and Ovarian Cancer syndrome: a systematic review

Isabela Ramos Forlin; Júlia Fernandes Silva; Eduardo Eiji Fernandes Seguchi; Clarissa  Torresan

doi:10.17765/2176-9206.2025v18e13100

Authors

Isabela Ramos Forlin Cesumar University https://orcid.org/0000-0001-5068-0823
Júlia Fernandes Silva Cesumar University https://orcid.org/0000-0002-7758-437X
Júlia Pontifical Catholic University of Campinas https://orcid.org/0009-0007-9202-3814
Clarissa Torresan Cesumar University https://orcid.org/0000-0001-8548-7150

DOI:

https://doi.org/10.17765/2176-9206.2025v18e13100

Keywords:

Hereditary Breast and Ovarian Cancer Syndrome, Genetic Testing, BRCA1 Gene, BRCA2 Gene

Abstract

Objective: This study aimed to perform a systematic literature review on the scenario of genetic predisposition testing for the Hereditary Breast and Ovarian Cancer Syndrome in Brazil and worldwide, specifically regarding the BRCA1 and BRCA2 genes. Method: Through the search of the keywords “Hereditary Breast and Ovarian Cancer Syndrome,” “Genetic Testing,” “BRCA1 Gene,” and “BRCA2 Gene,” and the application of exclusion and inclusion criteria. Results: The total of articles identified was 116,159, with 36 meeting the inclusion criteria. The results highlighted the importance of tailoring guidelines to meet the specific needs of different populations, crucial for patient follow-up, considering factors beyond the test itself. Conclusion: It was concluded that there is an advantage in identifying specific mutations in the demographic regions considering the country's great heterogeneity and that the inclusion of genetic predisposition testing for HBOC Syndrome in the Unified Health System is feasible and beneficial for the Brazilian population.

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Author Biographies

Isabela Ramos Forlin, Cesumar University

5th year (10th period) undergraduate student of Medicine at Cesumar University

Júlia Fernandes Silva, Cesumar University

5th year (10th period) undergraduate student of Medicine at Cesumar University

Júlia, Pontifical Catholic University of Campinas

6th year (12th period) undergraduate student of Medicine at the Pontifical Catholic University of Campinas

Clarissa Torresan, Cesumar University

PhD in Genetics from the Federal University of Paraná (2011) and Georgetown University - Washington DC, USA. Master's degree in Genetics (UFPR - 2006) and a degree in Biological Sciences from the Federal University of Santa Catarina (2004). Experience in Genetics, with emphasis on Human Genetics, Medical Genetics and Oncogenetics, working mainly on the following topics: breast cancer, CNVs, genetic polymorphisms, molecular genetic techniques and classical and molecular cytogenetics.

References

1. Macleod K. Tumor suppressor genes. Curr Opin Genet Dev. 1o de fevereiro de 2000;10(1):81–93. https://doi.org/10.1016/S0959-437X(99)00041-6

2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. novembro de 2018;68(6):394–424. https://doi.org/10.3322/caac.21492

3. Câncer - OPAS/OMS | Organização Pan-Americana da Saúde [Internet]. 2024 [citado 18 de novembro de 2024]. Disponível em: https://www.paho.org/pt/topicos/cancer

4. Cancer Tomorrow [Internet]. [citado 25 de novembro de 2024]. Disponível em: https://gco.iarc.who.int/today/

5. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12–49. https://doi.org/10.3322/caac.21820

6. Instituto Nacional de Câncer - INCA [Internet]. [citado 18 de novembro de 2024]. Estatísticas de câncer. Disponível em: https://www.gov.br/inca/pt-br/assuntos/cancer/numeros/estatisticas-de-cancer

7. Câncer de mama agora forma mais comum de câncer: OMS tomando medidas [Internet]. [citado 25 de novembro de 2024]. Disponível em: https://www.who.int/pt/news/item/03-02-2021-breast-cancer-now-most-common-form-of-cancer-who-taking-action

8. Teixeira LA, Araújo Neto LA. Câncer de mama no Brasil: medicina e saúde pública no século XX. Saúde E Soc. 2020;29(3):e180753. https://doi.org/10.1590/S0104-12902020180753

9. Rosenthal TC, Puck SM. Screening for Genetic Risk of Breast Cancer. Am Fam Physician. 1o de janeiro de 1999;59(1):99.

10. Amendola LCB, Vieira R. A contribuição dos genes BRCA na predisposição hereditária ao câncer de mama. Rev Bras Cancerol. 30 de dezembro de 2005;51(4):325–30. https://doi.org/10.32635/2176-9745.RBC.2005v51n4.1927

11. Pereira TL, Lima EV, Cardoso PB, Destro LRS, Mattos Z. MUTAÇÃO NOS GENES BRCA 1 E 2 E OS RISCOS PARA CÂNCER DE MAMA. 2019;2(2).

12. Marmolejo DH, Wong MYZ, Bajalica-Lagercrantz S, Tischkowitz M, Balmaña J, Patócs AB, et al. Overview of hereditary breast and ovarian cancer (HBOC) guidelines across Europe. Eur J Med Genet. dezembro de 2021;64(12):104350. https://doi.org/10.1016/j.ejmg.2021.104350

13. Pantoja REDL, Monteiro MCC, Nascimento BDS, Mota DAD, Balla IL, Rocha IMD, et al. A aplicação do mapeamento genético na identificação dos polimorfismos do câncer de mama e o direcionamento da terapia alvo. Res Soc Dev. 7 de agosto de 2022;11(10):e450111032762.

14. Sousa MC, Santos E Silva LD, Sousa CC. Diagnóstico de câncer de mama por exames genéticos: uma revisão de literatura. Braz J Health Rev. 2020;3(2):1786–97.

15. El Ansari FZ, Jouali F, Marchoudi N, Bennani MM, Ghailani NN, Barakat A, et al. Screening of BRCA1/2 genes mutations and copy number variations in patients with high risk for hereditary breast and ovarian cancer syndrome (HBOC). BMC Cancer. dezembro de 2020;20(1):747.

16. Narod SA. Screening for BRCA1 and BRCA2 mutations in breast cancer patients from mexico: the public health perspective. Salud Pública México. 2009;51:s191–6.

17. Buys SS, Sandbach JF, Gammon A, Patel G, Kidd J, Brown KL, et al. A study of over 35,000 women with breast cancer tested with a 25?gene panel of hereditary cancer genes. Cancer. 15 de maio de 2017;123(10):1721–30. https://doi.org/10.1002/cncr.30498

18. Graffeo R, Livraghi L, Pagani O, Goldhirsch A, Partridge AH, Garber JE. Time to incorporate germline multigene panel testing into breast and ovarian cancer patient care. Breast Cancer Res Treat. dezembro de 2016;160(3):393–410.

19. Achatz MI, Caleffi M, Guindalini R, Marques RM, Nogueira-Rodrigues A, Ashton-Prolla P. Recommendations for Advancing the Diagnosis and Management of Hereditary Breast and Ovarian Cancer in Brazil. JCO Glob Oncol. novembro de 2020;(6):439–52. https://doi.org/10.1200/JGO.19.00170

20. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. The BMJ. 29 de março de 2021;372:n71.

21. Cassundé FR de SA, Barbosa MAC, Mendonça JRC. Entre revisões sistemáticas e bibliometrias: como tem sido mapeada a produção acadêmica em Administração no Brasil? Informação Informação. 17 de dezembro de 2018;23(1):311–34. https://doi.org/10.5433/1981-8920.2018v23n1p311

22. Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. janeiro de 2006;3(2):77–101.

23. Meisel SF, Rahman B, Side L, Fraser L, Gessler S, et al. Genetic testing and personalized ovarian cancer screening: a survey of public attitudes. BMC Womens Health. dezembro de 2016;16(1):46.

24. White VB, Amacker-North L. Genetic Testing for Hereditary Breast Cancer: The Decision to Decline. The American SurgeonTM. 2018;84(1):154-160. https://doi.org/10.1177/000313481808400139

25. Sun Y, Kang E, Baek H, Jung J, Hwang E, Koo J, et al. Participation of Korean families at high risk for hereditary breast and ovarian cancer in BRCA1/2 genetic testing. Jpn J Clin Oncol. 2 de abril de 2015. https://doi.org/10.1093/jjco/hyv044

26. Jones T, McCarthy AM, Kim Y, Armstrong K. Predictors of BRCA 1/2 genetic testing among Black women with breast cancer: a population?based study. Cancer Med. julho de 2017;6(7):1787–98. https://doi.org/10.1002/cam4.1120

27. Rajagopal PS, Nielsen S, Olopade OI. USPSTF Recommendations for BRCA1 and BRCA2 Testing in the Context of a Transformative National Cancer Control Plan. JAMA Netw Open. 20 de agosto de 2019;2(8):e1910142. 10.1001/jamannetworkopen.2019.10142

28. McAlarnen L, Stearns K, Uyar D. Challenges of Genomic Testing for Hereditary Breast and Ovarian Cancers. Appl Clin Genet. janeiro de 2021;14:1–9. https://doi.org/10.2147/TACG.S245021

29. Randall TC, Armstrong K. Health Care Disparities in Hereditary Ovarian Cancer: Are We Reaching the Underserved Population? Curr Treat Options Oncol. agosto de 2016;17(8):39. https://doi.org/10.1007/s11864-016-0417-1

30. Beattie MS, Copeland K, Fehniger J, Cheung E, Joseph G, Lee R, et al. Genetic Counseling, Cancer Screening, Breast Cancer Characteristics, and General Health among a Diverse Population of BRCA Genetic Testers. J Health Care Poor Underserved. agosto de 2013;24(3):1150–66. https://doi.org/10.1353/hpu.2013.0151

31. Fox E, McCuaig J, Demsky R, Shuman C, Chitayat D, Maganti M, et al. The sooner the better: Genetic testing following ovarian cancer diagnosis. Gynecol Oncol. junho de 2015;137(3):423–9. https://doi.org/10.1016/j.ygyno.2015.03.057

32. Nilsson MP, Nilsson ED, Silfverberg B, Borg Å, Loman N. Written pretest information and germline BRCA1/2 pathogenic variant testing in unselected breast cancer patients: predictors of testing uptake. Genet Med. janeiro de 2019;21(1):89–96. https://doi.org/10.1038/s41436-018-0021-9

33. Nakagomi H, Sakamoto I, Hirotsu Y, Amemiya K, Mochizuki H, Inoue M, et al. Willingness of Japanese patients with breast cancer to have genetic testing of BRCA without burden of expenses. Breast Cancer. julho de 2016;23(4):649–53. https://doi.org/10.1007/s12282-015-0618-7

34. Nelson HD, Pappas M, Cantor A, Haney E, Holmes R. Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA- Related Cancer in Women: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 20 de agosto de 2019;322(7):666.

35. Stoll S, Unger S, Azzarello-Burri S, Chappuis P, Graffeo R, Pichert G, et al. Update Swiss guideline for counselling and testing for predisposition to breast, ovarian, pancreatic and prostate cancer. Swiss Med Wkly. 13 de setembro de 2021;151(3738):w30038. https://doi.org/10.4414/SMW.2021.w30038

36. Yip CH, Evans DG, Agarwal G, Buccimazza I, Kwong A, Morant R, et al. Global Disparities in Breast Cancer Genetics Testing, Counselling and Management. World J Surg. 15 de maio de 2019;43(5):1264–70. https://doi.org/10.1007/s00268-018-04897-6

37. Cragun D, Lewis C, Camperlengo L, Pal T. Hereditary Cancer: Example of a Public Health Approach to Ensure Population Health Benefits of Genetic Medicine. Healthcare. 8 de janeiro de 2016;4(1):6. https://doi.org/10.3390/healthcare4010006

38. Sullcahuaman Allende YC, Loarte Villarreal M, Torres Loarte M. Cáncer ginecológico hereditario en la era de la medicina genómica. Rev Peru Ginecol Obstet. 28 de setembro de 2018;64(3):461–8. http://dx.doi.org/https://doi.org/10.31403/rpgo.v64i2112

39. Eliade M, Skrzypski J, Baurand A, Jacquot C, Bertolone G, Loustalot C, et al. The transfer of multigene panel testing for hereditary breast and ovarian cancer to healthcare: What are the implications for the management of patients and families? Oncotarget. outubro de 2016;8:1957-1971. https://doi.org/10.18632/oncotarget.12699

40. Nunziato M, Scaglione GL, Di Maggio F, Nardelli C, Capoluongo E, Salvatore F. The performance of multi-gene panels for breast/ovarian cancer predisposition. Clin Chim Acta. janeiro de 2023;539:151–61. https://doi.org/10.1016/j.cca.2022.12.007

41. Thompson ER, Rowley SM, Li N, McInerny S, Devereux L, Wong-Brown MW, et al. Panel Testing for Familial Breast Cancer: Calibrating the Tension Between Research and Clinical Care. J Clin Oncol. 1o de maio de 2016;34(13):1455–9. https://doi.org/10.1200/JCO.2015.63.7454

42. US Preventive Services Task Force, Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, et al. Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA -Related Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 20 de agosto de 2019;322(7):652.

43. Daly MB, Pal T, Berry MP, Buys SS, Dickson P, Domchek SM, et al. Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 6 de janeiro de 2021;19(1):77–102. https://doi.org/10.6004/jnccn.2021.0001

44. Beitsch PD, Whitworth PW, Hughes K, Patel R, Rosen B, Compagnoni G, et al. Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle? J Clin Oncol. 20 de fevereiro de 2019;37(6):453–60. https://doi.org/10.1200/JCO.18.01631

45. Silva AVD, Rocha JCCD, Hospital Erasto Gaertner, Pontifícia Universidade Católica do Paraná, Guarneri GO, et al. Validation of NCCN criteria for genetic testing in HBOC syndrome in Brazil. Mastology. dezembro de 2017;27(4):271–5.

46. Hospital Erasto Gaertner, Guarneri GO, Ponte BJ, Hospital Erasto Gaertner, Ferreira JHF, Hospital Erasto Gaertner, et al. Genetic and demographic factors of a brazilian population sample at-risk of hereditary breast and ovarian cancer. Mastology. setembro de 2018;23(3):134–55.

47. Nguyen-Dumont T, Karpinski P, Sasiadek MM, Akopyan H, Steen JA, Theys D, et al. Genetic testing in Poland and Ukraine: should comprehensive germline testing of BRCA1 and BRCA2 be recommended for women with breast and ovarian cancer? Genet Res. 2020;102:e6.

48. Malhotra H, Kowtal P, Mehra N, Pramank R, Sarin R, Rajkumar T, et al. Genetic Counseling, Testing, and Management of HBOC in India: An Expert Consensus Document from Indian Society of Medical and Pediatric Oncology. JCO Glob Oncol. novembro de 2020;(6):991–1008. https://doi.org/10.1200/JGO.19.00381

49. D’Andrea E, Marzuillo C, De Vito C, Di Marco M, Pitini E, Vacchio MR, et al. Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluations. Genet Med. dezembro de 2016;18(12):1171–80.

50. Kotnik U, Peterlin B, Lovrecic L. Identification of women at risk for hereditary breast and ovarian cancer in a sample of 1000 Slovenian women: a comparison of guidelines. BMC Cancer. dezembro de 2021;21(1):665. https://doi.org/10.1186/s12885-021-08400-8

51. Arai M, Yokoyama S, Watanabe C, Yoshida R, Kita M, Okawa M, et al. Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan. J Hum Genet. abril de 2018;63(4):447–57. https://doi.org/10.1038/s10038-017-0355-1

52. Oosterwijk JC, De Vries J, Mourits MJ, De Bock GH. Genetic testing and familial implications in breast-ovarian cancer families. Maturitas. agosto de 2014;78(4):252–7.

53. D’Andrea E, Marzuillo C, Pelone F, Vito CD, Villari P. Genetic testing and economic evaluations: a systematic review of the literature. Epidemiol Prev. 2015;

54. Aganezov S, Goodwin S, Sherman RM, Sedlazeck FJ, Arun G, Bhatia S, et al. Comprehensive analysis of structural variants in breast cancer genomes using single-molecule sequencing. Genome Res. setembro de 2020;30(9):1258–73. http://www.genome.org/cgi/doi/10.1101/gr.260497.119

55. Hu C, Hart SN, Gnanaolivu R, Huang H, Lee KY, Na J, et al. A Population-Based Study of Genes Previously Implicated in Breast Cancer. N Engl J Med. 4 de fevereiro de 2021;384(5):440–51.

56. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1. Science. 7 de outubro de 1994;266(5182):66–71.

57. Sporikova Z, Koudelakova V, Trojanec R, Hajduch M. Genetic Markers in Triple-Negative Breast Cancer. Clin Breast Cancer. outubro de 2018;18(5):e841–50. 10.1016/j.clbc.2018.07.023

58. De Oliveira ES, Soares BL, Lemos S, Rosa RCA, Rodrigues AN, Barbosa LA, et al. Screening of the BRCA1 gene in Brazilian patients with breast and/or ovarian cancer via high-resolution melting reaction analysis. Fam Cancer. abril de 2016;15(2):173–81. 10.1007/s10689-015-9858-0

59. Moura JBD, Ghedin CC, Takakura ÉT, Scandolara TB, Rech D, Panis C. Hereditary Breast and Ovarian Cancer Screening Syndrome Profile in Women Diagnosed with Breast Cancer from Paraná State Southwest. Rev Bras Ginecol E Obstetrícia RBGO Gynecol Obstet. agosto de 2021;43(08):616–21. https://doi.org/10.1055/s-0041-1733998

60. Witjes VM, Ligtenberg MJL, Vos JR, Braspenning JCC, Ausems MGEM, Mourits MJE, et al. The most efficient and effective BRCA1/2 testing strategy in epithelial ovarian cancer: Tumor-First or Germline-First? Gynecol Oncol. julho de 2023;174:121–8. 10.1016/j.ygyno.2023.04.029

61. Zidekova D, Waczulikova I, Dolesova L, Vavrova L, Hamidova O, Lohajova Behulova R, et al. Rapid screening test of most frequent BRCA1/BRCA2 pathogenic variants in the NGS era. Neoplasma. 2018;65(02):309–15. 10.4149/neo_2018_170507N328

62. Hayashi S, Kubo M, Kaneshiro K, Kai M, Yamada M, Morisaki T, et al. Genetic medicine is accelerating in Japan. Breast Cancer. julho de 2022;29(4):659–65. 10.1007/s12282-022-01342-4

63. Neusser S, Lux B, Barth C, Pahmeier K, Rhiem K, Schmutzler R, et al. The budgetary impact of genetic testing for hereditary breast cancer for the statutory health insurance. Curr Med Res Opin. 2 de dezembro de 2019;35(12):2103–10. 10.1080/03007995.2019.1654689

64. Moreno L, Linossi C, Esteban I, Gadea N, Carrasco E, Bonache S, et al. Germline BRCA testing is moving from cancer risk assessment to a predictive biomarker for targeting cancer therapeutics. Clin Transl Oncol. outubro de 2016;18(10):981–7. 10.1007/s12094-015-1470-0

65. Ramos MCDA, Folgueira MAAK, Maistro S, Campolina AG, Soárez PCD, Bock GHD, et al. Cost effectiveness of the cancer prevention program for carriers of the BRCA1/2 mutation. Rev Saúde Pública. 22 de novembro de 2018;52:94. https://doi.org/10.11606/S1518-8787.2018052000643

66. Mighton C, Shickh S, Aguda V, Krishnapillai S, Adi-Wauran E, Bombard Y. From the patient to the population: Use of genomics for population screening. Front Genet. 24 de outubro de 2022;13:893832. https://doi.org/10.3389/fgene.2022.893832

67. Evans O, Gaba F, Manchanda R. Population-based genetic testing for Women’s cancer prevention. Best Pract Res Clin Obstet Gynaecol. maio de 2020;65:139–53. https://doi.org/10.1016/j.bpobgyn.2020.02.007

68. Kwong A, Shin VY, Au CH, Law FBF, Ho DN, Ip BK, et al. Detection of Germline Mutation in Hereditary Breast and/or Ovarian Cancers by Next-Generation Sequencing on a Four-Gene Panel. J Mol Diagn. julho de 2016;18(4):580–94. 10.1016/j.jmoldx.2016.03.005