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CC BY 4.0 · Brazilian Journal of Oncology 2021; 17: e-20210024
DOI: 10.5935/2526-8732.20210024
Original Article
Clinical Oncology

Ovarian cancer and BRCA mutation genetic testing: the Brazilian reality

Câncer de ovário e teste genético de mutação BRCA: a realidade brasileira

Dalila Cunha de Oliveira
1   Astrazeneca do Brasil, Medical - Cotia - Sao Paulo - Brazil
,
Luciana Lopes Mensor
2   Astrazeneca do Brasil, Market Access - Cotia - Sao Paulo - Brazil
,
Aniere Lima Banho
1   Astrazeneca do Brasil, Medical - Cotia - Sao Paulo - Brazil
,
Guareide Carelli
1   Astrazeneca do Brasil, Medical - Cotia - Sao Paulo - Brazil
,
Amanda Lins Acerbi
3   Astrazeneca do Brasil, Diagnostics - Cotia - Sao Paulo - Brazil
,
Andrea Paiva Gadelha Guimaraes
4   A.C. Camargo Cancer Center, Medical Oncology - Sao Paulo - Sao Paulo - Brazil
,
Angelica Nogueira-Rodrigues
5   Minas Gerais Federal University, Internal Medicine, Faculty of Medicine - Belo Horizonte - Minas Gerais - Brazil
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ABSTRACT

Introduction: Ovarian cancer (OC) is one of the leading causes of women's cancer deaths worldwide. Recent clinical trials with PARP inhibitors showed promising therapeutic opportunities for OC patients. The assessment of BRCA mutation is well established as relevant in the prevention, early diagnostic, and family counseling for OC, and recently BRCA gene mutation was associated as a prognosis for PARP inhibitors treatment. In this scenario, the assessment of the patient's mutation is proposed on Brazilian oncology guidelines and should be advised by health professionals that treat OC. Objectives: Inquire Brazilian oncologists about BRCA gene testing requesting time in the clinical practice for OC patients. Material and Methods: From May 2018 to June 2019, approximately 400 Brazilian oncologists received an online survey with questions related to the indication and challenges of BRCA gene testing. The survey was sent in 4 periods (waves); each wave received approximately 100 answers. Results: The compiled information showed that, on average, each oncologist treated 3 to 5 patients with ovarian cancer, they would recommend testing for three patients. Most respondents would indicate, BRCA testing during patients initial diagnostic period (w1=44%, w2=50%, w3=58%, and w4=64%). The sample of choice for testing would be blood/saliva assessing the germline mutational status (w1=35%, w2=43%, w3=46%, and w4=47%). The main reasons for oncologists to refrain from recommending BRCA testing were associated with cost and lack of reimbursement followed by lack of genetic counselors, among other factors. Conclusion: BRCA testing is restricted and not recommended for all ovarian cancer patients from the private health care sector. There is a lack of consensus on testing recommendations and discrepancies between coverage and national guidelines standardizing. There main difficulties associated with refraining testing were related to reimbursement and health plan coverage. Besides, the lack of genetic counseling was also pointed to as a bottleneck on oncologic patients' multidisciplinary treatment.

RESUMO

Introdução: O câncer de ovário (CO) é uma das principais causas de mortes por câncer de mulheres em todo o mundo. Ensaios clínicos recentes com inibidores de PARP mostraram oportunidades terapêuticas promissoras para pacientes com CO. A avaliação da mutação BRCA é bem estabelecida como relevante na prevenção, diagnóstico precoce e aconselhamento familiar para CO, e recentemente a mutação do gene BRCA foi associada como um prognóstico para o tratamento com inibidores de PARP. Nesse cenário, a avaliação da mutação do paciente é proposta nas diretrizes brasileiras de oncologia e deve ser orientada pelos profissionais de saúde que tratam da CO. Objetivos: Investigar oncologistas brasileiros sobre o teste do gene BRCA, questionando o momento da testagem na prática clinica para pacienets com CO. Material e Métodos: De maio de 2018 a junho de 2019, aproximadamente 400 oncologistas brasileiros receberam uma pesquisa online com perguntas relacionadas à indicação e desafios do teste do gene BRCA. A pesquisa foi enviada em 4 períodos (ondas); cada onda recebeu aproximadamente 100 respostas. Resultados: As informações compiladas mostraram que, em média, cada oncologista tratou de 3 a 5 pacientes com câncer de ovário, eles recomendariam o teste para três pacientes. A maioria dos entrevistados indicaria o teste BRCA durante o período inicial de diagnóstico dos pacientes (w1=44%, w2=50%, w3=58% e w4=64%). A amostra de escolha para teste seria sangue/saliva avaliando o status mutacional da linha germinativa (w1=35%, w2=43%, w3=46% e w4=47%). Os principais motivos pelos quais os oncologistas se abstiveram de recomendar o teste BRCA foram associados ao custo e à falta de reembolso, seguidos de falta de conselheiros genéticos, entre outros fatores. Conclusão: O teste BRCA é restrito e não recomendado para todas as pacientes com câncer de ovário do setor privado de saúde. Há uma falta de consenso sobre as recomendações de teste e discrepâncias entre a cobertura e a padronização das diretrizes nacionais. As principais dificuldades associadas ao teste de abstinência foram relacionadas ao reembolso e à cobertura do plano de saúde. Além disso, a falta de aconselhamento genético também foi apontada como um gargalo no tratamento multidisciplinar de pacientes oncológicos.

Keywords:

Medical oncology - Clinical medicine - Ovarian diseases - Genetic counseling - Genes - Practice guideline.

Descritores:

Oncologia médica - Medicina Clínica - Doenças ovarianas - Aconselhamento genético - Genes - Diretriz prática de genes.

CONFLICT OF INTEREST

DCO, LM, ALM, GC, AA work for AstraZeneca Brazil.


CONTRIBUTIONS

All authors approved the final manuscript version and organized the data, designed and analyzed the manuscript.

Ipsos do BRASIL conducted the survey. DCO was the medical writer.


Financial support: AstraZeneca Brazil supported this work. The authors ANR and AG did not receive any honoraria for participating in this research.


FUNDING

AstraZeneca Brazil supported this work. However, the authors ANR and AG did not receive any honoraria for participating in organization, design, data analysis, and manuscript review. During the development of this work, LM changed institution filiation as MBA in Economy and Health Technologies Assessment visiting professor at FIPE ( Fundação Instituto de Pesquisa ).


DECLARATIONS ETHICS APPROVAL

No institutional ethics approval was required.




Publication History

Received: 08 March 2021

Accepted: 23 July 2021

Article published online:
23 August 2021

© 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Bibliographical Record
Dalila Cunha de Oliveira, Luciana Lopes Mensor, Aniere Lima Banho, Guareide Carelli, Amanda Lins Acerbi, Andrea Paiva Gadelha Guimaraes, Angelica Nogueira-Rodrigues. Ovarian cancer and BRCA mutation genetic testing: the Brazilian reality. Brazilian Journal of Oncology 2021; 17: e-20210024.
DOI: 10.5935/2526-8732.20210024
 

  • REFERENCES

  • Ministério da Saúde (BR). Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA). Estimativa 2020: incidência de câncer no Brasil. Rio de Janeiro: Ministério da Saúde/INCA;; 2019
    Search in Google Scholar
  • Rojas V, Hirshfield K, Ganesan S, RodriguezRodriguez L.. Molecular characterization of epithelial ovarian cancer: implications for diagnosis and treatment. Int J Mol Sci 2016; Dec; 17 (12) 2113
    Search in Google Scholar
  • Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M. et al Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018; Dec; 379 (26) 2495-2505
    Search in Google Scholar
  • National Comprehensive Cancer Network (NCCN). Ovarian cancer (version 2.2020) [Internet]. Plymouth Meeting: NCCN;; 2020. access in 2021 Jan 26 Available from: https://www.nccn.org/professionals/physician_gls/pdf/ovarian_blocks.pdf
    Search in Google Scholar
  • Konstantinopoulos PA, Norquist B, Lacchetti C, Armstrong D, Grisham RN, Goodfellow PJ. et al Germline and somatic tumor testing in epithelial ovarian cancer: ASCO Guideline. J Clin Oncol 2020; Apr; 38 (11) 1222-1245
    Search in Google Scholar
  • Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R. et al Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med 2019; Dec; 381 (25) 2416-2428
    Search in Google Scholar
  • Chavarri-Guerra Y, Blazer KR, Weitzel JN.. Genetic cancer risk assessment for breast cancer in Latin America. Rev Invest Clin 2017; Mar/Apr; 69 (02) 94-102
    Search in Google Scholar
  • Palmero EI, Carraro DM, Alemar B, Moreira MAM, Ribeiro-Dos-Santos Â, Abe-Sandes K. et al The germline mutational landscape of BRCA1 and BRCA2 in Brazil. Sci Rep 2018; Jun; 8 (01) 9188
    Search in Google Scholar
  • Fumagalli C, Tomao F, Betella I, Rappa A, Calvello M, Bonanni B. et al Tumor BRCA test for patients with epithelial ovarian cancer: the role of molecular pathology in the era of PARP inhibitor therapy. Cancers 2019; Oct; 11 (11) 1641
    Search in Google Scholar
  • Gonçalves S, Abuin GG, Gallardo D, Estevez Diz P, Caceres V, De la Vega M. et al 11 Flabra, frontline approach for BRCA testing in ovarian cancer (OC) treatment naïve population. A Latin America (LA) epidemiologic study. Int J Gynecol Cancer [Internet] 2019; [cited 2021 Jan 27]; 29 (Suppl 3): A7 Available from: https://ijgc.bmj.com/lookup/doi/10.1136/ijgc-2019-IGCS.11
    Search in Google Scholar
  • Giornelli G, Gallardo D, Hegg R, Abuin GG, La Vega MD, Lim-Law M. et al FLABRA, frontline approach for BRCA testing in an ovarian cancer population: a Latin America epidemiologic study. Future Oncol 2021; May; 17 (13) 1601-1609
    Search in Google Scholar
  • Kwong A, Cheng KD, Hsue CV, Hui S, Leung CR, Leung KA. et al BRCA mutation testing for ovarian cancer in the context of available targeted therapy: survey and consensus of Hong Kong specialists. Asia Pac J Clin Oncol 2019; Mar; 15 (Suppl 2): 20-31
    Search in Google Scholar
  • Vergote I, Banerjee S, Gerdes AM, Van Asperen C, Marth C, Vaz F. et al Current perspectives on recommendations for BRCA genetic testing in ovarian cancer patients. Eur J Cancer 2016; Dec; 69: 127-134
    Search in Google Scholar
  • Colombo N, Huang G, Scambia G, Chalas E, Pignata S, Fiorica J. et al Evaluation of a streamlined oncologist-led BRCA mutation testing and counseling model for patients with ovarian cancer. J Clin Oncol 2018; May; 36 (13) 1300-1307
    Search in Google Scholar
  • Goldberg JM, Piver MS, Hempling RE, Recio FO.. Paclitaxel and cisplatin combination chemotherapy in recurrent epithelial ovarian cancer. Gynecol Oncol 1996; Dec; 63 (03) 312-317
    Search in Google Scholar
  • Van Zyl B, Tang D, Bowden NA.. Biomarkers of platinum resistance in ovarian cancer: what can we use to improve treatment?. Endocr Relat Cancer 2018; May; 25 (05) R303-18
    Search in Google Scholar
  • Gupta S, Nag S, Aggarwal S, Rauthan A, Warrier N.. Maintenance therapy for recurrent epithelial ovarian cancer: current therapies and future perspectives - a review. J Ovarian Res 2019; Nov; 12 (01) 103
    Search in Google Scholar
  • Burke W, Daly M, Garber J, Botkin J, Kahn MJ, Lynch P. et al Recommendations for follow-up care of individuals with an inherited predisposition to cancer: II. BRCA1 and BRCA2. JAMA 1997; Mar; 277 (12) 997-1003
    Search in Google Scholar
  • 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 1994; Oct; 266 (5182) 66-71
    Search in Google Scholar
  • Turan V, Oktay K.. BRCA-related ATM-mediated DNA double-strand break repair and ovarian aging. Hum Reprod Update 2020; Jan; 26 (01) 43-57
    Search in Google Scholar
  • Hanahan D, Weinberg RA.. Hallmarks of cancer: the next generation. Cell 2011; Mar; 144 (05) 646-674
    Search in Google Scholar
  • Murfuni I, Rass U.. Targeting homologous recombination repair in cancer. Kelley MR, Fishel ML. DNA repair in cancer therapy [Internet]. Amsterdam: Elsevier; 2016. access in 2021 Jan 27 225-275 Available from: https://linkinghub.elsevier.com/retrieve/pii/B9780128035825000085
    Search in Google Scholar
  • Hoppe MM, Sundar R, Tan DSP, Jeyasekharan AD.. Biomarkers for homologous recombination deficiency in cancer. J Natl Cancer Inst 2018; Jul; 110 (07) 704-713
    Search in Google Scholar
  • Ledermann JA, Pujade-Lauraine E.. Olaparib as maintenance treatment for patients with platinum-sensitive relapsed ovarian cancer. Ther Adv Med Oncol 2019; Jan; 11: 175883591984975
    Search in Google Scholar
  • Kummar S, Chen A, Parchment RE, Kinders RJ, Ji J, Tomaszewski JE. et al Advances in using PARP inhibitors to treat cancer. BMC Med 2012; Dez; 10 (01) 25
    Search in Google Scholar
  • Longo DL.. Personalized medicine for primary treatment of serous ovarian cancer. N Engl J Med 2019; Dez; 381 (25) 2471-2474
    Search in Google Scholar
  • Knabben L, Imboden S, Mueller MD.. Genetic testing in ovarian cancer - clinical impact and current practices. Horm Mol Biol Clin Investig [Internet] 2019; [Oct cited 2021 Jan 27]; 41 (03) 20190025 Available from: https://www.degruyter.com/view/journals/hmbci/41/3/article-20190025.xml
    Search in Google Scholar
  • Miotto BA, Guilloux AGA, Cassenote AJF, Mainardi GM, Russo G, Scheffer MC.. Physician's sociodemographic profile and distribution across public and private health care: an insight into physicians' dual practice in Brazil. BMC Health Serv Res 2018; Dec; 18 (01) 299
    Search in Google Scholar
  • Póvoa L, Andrade MV.. Distribuição geográfica dos médicos no Brasil: uma análise a partir de um modelo de escolha locacional. Cad Saúde Pública 2006; Aug; 22 (08) 1555-1564
    Search in Google Scholar
  • Meyer L, Wright JD, Downer MK, Incerti D, Luhn P, Dolado I. et al Patterns and adoption of BRCA testing in ovarian cancer in the real world: observations from Flatiron Health. In: Annual Meeting on Women's Cancer - Society of Gynecologic Oncology (SGO) 2020 - Abstract 113 [Internet]. Chicago, Illinois, United States: 28 Mar 2020 Chicago: SGO; 2020. Available from: https://sgo.confex.com/sgo/2020/meetingapp.cgi/Paper/15085
    Search in Google Scholar
  • Sales LAP, Lajus TBP. Aconselhamento genético em oncologia no Brasil 2018; Dec; 97 (05) 448-453
    Search in Google Scholar
  • Capoluongo E, Ellison G, López-Guerrero JA, Penault-Llorca F, Ligtenberg MJL, Banerjee S. et al Guidance statement On BRCA1/2 tumor testing in ovarian cancer patients. Semin Oncol 2017; Jun; 44 (03) 187-197
    Search in Google Scholar
  • Eccleston A, Bentley A, Dyer M, Strydom A, Vereecken W, George A. et al A cost- effectiveness evaluation of germline BRCA1 and BRCA2 testing in UK women with ovarian cancer. Value Health 2017; Apr; 20 (04) 567-576
    Search in Google Scholar
  • Malta DC, Stopa SR, Pereira CA, Szwarcwald CL, Oliveira M, Reis AC.. Cobertura de planos de saúde na população brasileira, segundo a Pesquisa Nacional de Saúde, 2013. Ciênc Saúde Colet 2017; Jan; 22 (01) 179-190
    Search in Google Scholar
  • Ministério da Saúde (BR). Agência Nacional de Saúde Suplementar (ANS). Dados Gerais - Beneficiários de planos privados de saúde, por cobertura assistencial (Brasil - 2009-2019). Brasília (DF): Ministério da Saúde;; 2020
    Search in Google Scholar
  • Alsop K, Fereday S, Meldrum C, Fazio A, Emmanuel C, George J. et al 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; 30 (21) 2654-2663
    Search in Google Scholar
  • Di Resta C, Ferrari M. Next generation sequencing: from research area to clinical practice. EJIFCC 2018; Nov; 29 (03) 215-220
    Search in Google Scholar