A IMPORTÂNCIA DA CLASSIFICAÇÃO MOLECULAR NO PROGNÓSTICO DO CÂNCER DE MAMA: PERSPECTIVAS ATUAIS
DOI:
https://doi.org/10.37951/refacer.v10i1.5879Palavras-chave:
Câncer de mama., Diagnósticos moleculares., Prognóstico.Resumo
INTRODUÇÃO: O conhecimento sobre a classificação molecular do câncer de mama tem se
tornado cada vez mais importante para definição de protocolos de tratamento, principalmente
terapias alvo direcionadas. OBJETIVO: Descrever por meio da literatura a prevalência dos
subtipos moleculares do câncer de mama, e sua relação com o prognóstico de indivíduos
diagnosticados com esses tumores. METODOLOGIA: Trata-se de uma revisão integrativa
da literatura que incluiu artigos que investigaram os principais subtipos moleculares do câncer
de mama (Luminal A, Luminal B, HER2/neu e Basa-like), e excluiu as publicações que
investigaram apenas a expressão de marcadores moleculares como por exemplo p53 e HER2,
ou que fizeram apenas a classificação histopatológica, sem considerar a classificação
molecular para câncer de mama. RESULTADOS E DISCUSSÕES: Um total de 29,850
casos de câncer de mama em mulheres, obteve o resultado do subtipo da classificação
molecular, o mais prevalente foi o luminal A (51,3%%), seguido do luminal B (18%), HER2
(7,9%), basa-like (7,1%), a prevalência do triplo-negativo também foi investigada com
(5,5%). O luminal A oferece o melhor prognóstico de todos os subtipos, os tumores luminais
B são menos favoráveis do que os tumores luminais A, mas ainda menos agressivos do que os
tumores do tipo basal. CONCLUSÃO: O luminal A continua sendo o subtipo molecular mais
prevalente para o câncer de mama. O conhecimento sobre as classes moleculares do câncer de
mama aumentou nos últimos anos, porém ainda existem dúvidas e dilemas que permanecem
sem resposta e que são importantes para estudos futuros.
Palavras-chaves: Câncer de mama. Diagnósticos moleculares. Prognóstico.
Referências
ABDELKRIM, S. BEN et al. Distribution of molecular breast cancer subtypes among
Tunisian women and correlation with histopathological parameters: A study of 194 patients.
Pathology Research and Practice, v. 206, n. 11, p. 772–775, 2010.
ABREU, E. DE; KOIFMAN, S. Fatores prognósticos no câncer da mama feminina. Revista
Brasileira de Cancerologia, v. 48, n. 1, p. 113–131, 2002.
AKOZ, G. et al. Evaluation of human epididymal secretory protein 4 expression according to
the molecular subtypes (luminal A, luminal B, human epidermal growth factor receptor 2-
positive, triple-negative) of breast cancer. Indian Journal of Pathology and Microbiology,
v. 61, n. 3, p. 323–329, 2018.
AL-THOUBAITY, F. K. Molecular classification of breast cancer: A retrospective cohort
study. Annals of Medicine and Surgery, v. 49, n. October 2019, p. 44–48, 2020.
AL TAMIMI, D. M. et al. Protein expression profile and prevalence pattern of the molecular
classes of breast cancer - a Saudi population based study. BMC Cancer, v. 10, 2010.
ALI, H. R. et al. Genome-driven integrated classification of breast cancer validated in over
7,500 samples. Genome Biology, v. 15, n. 8, p. 1–14, 2014.
ANDERSON, W. F. et al. Comparison of age distribution patterns for different
histopathologic types of breast carcinoma. Cancer Epidemiology Biomarkers and
Prevention, v. 15, n. 10, p. 1899–1905, 2006.
ARSLAN, E. et al. Role of 18F-FDG PET/CT in evaluating molecular subtypes and
clinicopathological features of primary breast cancer. Nuclear Medicine Communications,
v. 39, n. 7, p. 680–690, 2018.
BARRETO-NETO, N. J. DE S. et al. Perfil epidemiológico dos subtipos moleculares de
carcinoma ductal da mama em população de pacientes em Salvador, Bahia. Revista
Brasileira de Mastologia, v. 24, n. 4, p. 98–102, 12 set. 2014.
BENNIS, S. et al. Prevalence of molecular subtypes and prognosis of invasive breast cancer
in north-east of Morocco: Retrospective study. BMC Research Notes, v. 5, 2012.
BRASIL. Fatores de risco para o câncer de mama. Disponível em:
<https://www.inca.gov.br/controle-do-cancer-de-mama/fatores-de-risco>. Acesso em: 30 nov.
2021.
BRASIL. Câncer de mama/ controle do câncer/ INCA. Disponível em:
<https://www.inca.gov.br/controle-do-cancer-de-mama/conceito-e-magnitude>. Acesso em:
12 mar. 2020.
BRENTON, J. D. et al. Molecular classification and molecular forecasting of breast cancer:
Ready for clinical application? Journal of Clinical Oncology, v. 23, n. 29, p. 7350–7360,
2005.
BUJOR, I. S. et al. Evaluation of vascular proliferation in molecular subtypes of breast
cancer. In Vivo, v. 32, n. 1, p. 79–83, 2018.
CAREY, L. A. et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer
Study. Journal of the American Medical Association, v. 295, n. 21, p. 2492–2502, 2006.
CAREY, L. A. et al. The triple negative paradox: Primary tumor chemosensitivity of breast
cancer subtypes. Clinical Cancer Research, v. 13, n. 8, p. 2329–2334, 2007.
CHEANG, M. C. U. et al. Ki67 Index , HER2 Status , and Prognosis of Patients With
Luminal B Breast Cancer. J Natl Cancer Inst, v. 101, n. 10, p. 736–750, 2009.
CIRQUEIRA, M. B. et al. Subtipos moleculares do câncer de mama. Femina, v. 39, 2011.
EDGE, S. B.; COMPTON, C. C. The american joint committee on cancer: The 7th edition of
the AJCC cancer staging manual and the future of TNM. Annals of Surgical Oncology, v.
17, n. 6, p. 1471–1474, 2010.
EISENBERG, A. L. A.; KOIFMAN, E S. Câncer de mama: marcadores tumorais. Revista
Brasileira de Cancerologia, p. 337–338, 2001.
EL-HAWARY, A. K. et al. Molecular subtypes of breast carcinoma in Egyptian women:
Clinicopathological features. Pathology Research and Practice, v. 208, n. 7, p. 382–386,
2012.
ELIYATKIN, N. Molecular Classification of Breast Carcinoma: From Traditional, OldFashioned Way to A New Age, and A New Way. J Breast Health, p. 59–66, 2015.
ELKABLAWY, M. A. et al. Molecular profiling of breast carcinoma in Almadinah, KSA:
Immunophenotyping and clinicopathological correlation. Asian Pacific Journal of Cancer
Prevention, v. 16, n. 17, p. 7819–7824, 2015.
FATEMI, H. EL et al. Luminal B tumors are the most frequent molecular subtype in breast
cancer of North African women : an immunohistochemical profile study from Morocco.
Diagnostic Pathology, p. 1–7, 2012.
FOURATI, A. et al. Descriptive analysis of molecular subtypes in Tunisian breast cancer.
Asia-Pacific Journal of Clinical Oncology, v. 10, n. 2, 2012.
FRAGOMENI, S. M.; SCIALLIS, A.; JERUSS, J. S. Molecular Subtypes and Local-Regional
Control of Breast Cancer. Surgical Oncology Clinics of North America, v. 27, n. 1, p. 95–
120, 2018.
GOLDHIRSCH, A. et al. Strategies for subtypes-dealing with the diversity of breast cancer:
Highlights of the St Gallen international expert consensus on the primary therapy of early
breast cancer 2011. Annals of Oncology, v. 22, n. 8, p. 1736–1747, 2011.
HASHMI, A. A. et al. Prognostic parameters of luminal A and luminal B intrinsic breast
cancer subtypes of Pakistani patients. World Journal of Surgical Oncology, v. 16, n. 1, p. 1–
6, 2018.
IARC. Número estimado de casos de incidentes em todo o mundo, mulheres, todas as
idades. Disponível em: <http://gco.iarc.fr/today/online-analysis-multi-bars>. Acesso em: 1
abr. 2021.
IHEMELANDU, C. U.; LEFFALL, L. D.; DEWITTY, R. L. Molecular Breast Cancer
Subtypes in Premenopausal and Postmenopausal African-American Women : Age-Specific
Prevalence and Survival. Journal of Surgical Research, v. 118, p. 109–118, 2007.
KADIVAR, M. et al. Breast cancer molecular subtypes and associations with
clinicopathological characteristics in Iranian women, 2002-2011. Asian Pacific Journal of
Cancer Prevention, v. 13, n. 5, p. 1881–1886, 2012.
LI, J. et al. Clinicopathological classification and traditional prognostic indicators of breast
cancer. International Journal of Clinical and Experimental Pathology, v. 8, n. 7, p. 8500–
8505, 2015.
LONG, Q. et al. Overexpression of lncrna tatdn1 promotes cancer cell proliferation in triple
negative breast cancer by regulating mir-26b methylation. Cancer Management and
Research, v. 12, p. 11403–11410, 2020.
LUNDGREN, C. et al. Agreement between molecular subtyping and surrogate subtype
classification: a contemporary population-based study of ER-positive/HER2-negative primary
breast cancer. Breast Cancer Research and Treatment, v. 178, n. 2, p. 459–467, 2019.
MENDONÇA, G. A. E S.; SILVA, A. M. DA; CAULA, W. M. Características tumorais e
sobrevida de cinco anos em pacientes com câncer de mama admitidas no Instituto Nacional de
Câncer, Rio de Janeiro, Brasil. Cadernos de Saúde Pública, v. 20, n. 5, p. 1232–1239, out.
2004.
MILIOLI, H. H. et al. Basal-like breast cancer : molecular profiles , clinical features and
survival outcomes. BMC Medical Genomics, p. 1–17, 2017.
MUNJAL, K. et al. Immunohistochemical Analysis of ER, PR, Her2 and CK5/6 in Infiltrative
Breast Carcinomas in Indian Patients. Asian Pacific Journal of Cancer Prevention, v. 10, p.
773–778, 2009.
NGUYEN, P. L. et al. Breast cancer subtype approximated by estrogen receptor, progesterone
receptor, and HER-2 is associated with local and distant recurrence after breast-conserving
therapy. Journal of Clinical Oncology, v. 26, n. 14, p. 2373–2378, 2008.
ONITILO, A. A. et al. Breast Cancer Subtypes Based on ER/PR and Her2 Expression:
Comparison of Clinicopathologic Features and Survival. Clinical Medicine & Research, v.
7, n. 1–2, p. 4–13, 2009.
PRAT, A. et al. Molecular Characterization of Basal-Like and Non-Basal-Like TripleNegative Breast Cancer. TheOncologist, p. 123–133, 2013.
RAKHA, E. A. et al. Breast cancer prognostic classification in the molecular era: The role of
histological grade. Breast Cancer Research, v. 12, n. 4, 2010.
RECǍREANU, F. et al. Ductal invasive mammary carcinoma - Clinicopathological
prognostic factors related to immunohistochemical expression of hormonal receptors and
Her2/neu oncoprotein. Romanian Journal of Morphology and Embryology, v. 52, n. 3
SUPPL., p. 1059–1064, 2012.
SALHIA, B. et al. Molecular subtype analysis determines the association of advanced breast
cancer in Egypt with favorable biology. BMC Women’s Health, v. 11, 2011.
SERRA, K. P. et al. Nova classificação dos carcinomas da mama: Procurando o luminal a.
Revista Brasileira de Ginecologia e Obstetricia, v. 36, n. 12, p. 575–580, 2014.
SILVA, P. A. DA; RIUL, S. DA S. Breast cancer: risk factors and early detection. Revista
brasileira de enfermagem, v. 64, n. 6, p. 1016–1021, 2011.
SIMON, R. et al. Pitfalls in the use of DNA microarray data for diagnostic and prognostic
classification. Journal of the National Cancer Institute, v. 95, n. 1, p. 14–18, 2003.
SPITALE, A. et al. Breast cancer classification according to immunohistochemical markers:
Clinicopathologic features and short-term survival analysis in a population-based study from
the South of Switzerland. Annals of Oncology, v. 20, n. 4, p. 628–635, 2009.
STIVAL, R. A. et al. Impacto do fenótipo triplo-negativo no prognóstico de pacientes com
câncer de mama de uma unidade de referência no Brasil central. Rev Bras Mastologia, p. 6–
12, 2012.
VALLEJOS, C. et al. Breast cancer classification according to immunohistochemistry
markers: Subtypes and association with clinicopathologic variables in a peruvian hospital
database. Clinical Breast Cancer, v. 10, n. 4, p. 294–300, 2010.
VIALE, G. The current state of breast cancer classification. Annals of Oncology, v. 23, n.
SUPPL. 10, 2012.
VIEIRA, D. S. C. et al. Carcinoma de mama: Novos conceitos na classificação. Revista
Brasileira de Ginecologia e Obstetricia, v. 30, n. 1, p. 42–47, 2008.
WIECHMANN, L. et al. Presenting features of breast cancer differ by molecular subtype.
Annals of Surgical Oncology, v. 16, n. 10, p. 2705–2710, 2009.
WOLFF, A. C. et al. American Society of Clinical Oncology/College of American
Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing
in breast cancer. Journal of Clinical Oncology, v. 25, n. 1, p. 118–145, 2007.
Tunisian women and correlation with histopathological parameters: A study of 194 patients.
Pathology Research and Practice, v. 206, n. 11, p. 772–775, 2010.
ABREU, E. DE; KOIFMAN, S. Fatores prognósticos no câncer da mama feminina. Revista
Brasileira de Cancerologia, v. 48, n. 1, p. 113–131, 2002.
AKOZ, G. et al. Evaluation of human epididymal secretory protein 4 expression according to
the molecular subtypes (luminal A, luminal B, human epidermal growth factor receptor 2-
positive, triple-negative) of breast cancer. Indian Journal of Pathology and Microbiology,
v. 61, n. 3, p. 323–329, 2018.
AL-THOUBAITY, F. K. Molecular classification of breast cancer: A retrospective cohort
study. Annals of Medicine and Surgery, v. 49, n. October 2019, p. 44–48, 2020.
AL TAMIMI, D. M. et al. Protein expression profile and prevalence pattern of the molecular
classes of breast cancer - a Saudi population based study. BMC Cancer, v. 10, 2010.
ALI, H. R. et al. Genome-driven integrated classification of breast cancer validated in over
7,500 samples. Genome Biology, v. 15, n. 8, p. 1–14, 2014.
ANDERSON, W. F. et al. Comparison of age distribution patterns for different
histopathologic types of breast carcinoma. Cancer Epidemiology Biomarkers and
Prevention, v. 15, n. 10, p. 1899–1905, 2006.
ARSLAN, E. et al. Role of 18F-FDG PET/CT in evaluating molecular subtypes and
clinicopathological features of primary breast cancer. Nuclear Medicine Communications,
v. 39, n. 7, p. 680–690, 2018.
BARRETO-NETO, N. J. DE S. et al. Perfil epidemiológico dos subtipos moleculares de
carcinoma ductal da mama em população de pacientes em Salvador, Bahia. Revista
Brasileira de Mastologia, v. 24, n. 4, p. 98–102, 12 set. 2014.
BENNIS, S. et al. Prevalence of molecular subtypes and prognosis of invasive breast cancer
in north-east of Morocco: Retrospective study. BMC Research Notes, v. 5, 2012.
BRASIL. Fatores de risco para o câncer de mama. Disponível em:
<https://www.inca.gov.br/controle-do-cancer-de-mama/fatores-de-risco>. Acesso em: 30 nov.
2021.
BRASIL. Câncer de mama/ controle do câncer/ INCA. Disponível em:
<https://www.inca.gov.br/controle-do-cancer-de-mama/conceito-e-magnitude>. Acesso em:
12 mar. 2020.
BRENTON, J. D. et al. Molecular classification and molecular forecasting of breast cancer:
Ready for clinical application? Journal of Clinical Oncology, v. 23, n. 29, p. 7350–7360,
2005.
BUJOR, I. S. et al. Evaluation of vascular proliferation in molecular subtypes of breast
cancer. In Vivo, v. 32, n. 1, p. 79–83, 2018.
CAREY, L. A. et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer
Study. Journal of the American Medical Association, v. 295, n. 21, p. 2492–2502, 2006.
CAREY, L. A. et al. The triple negative paradox: Primary tumor chemosensitivity of breast
cancer subtypes. Clinical Cancer Research, v. 13, n. 8, p. 2329–2334, 2007.
CHEANG, M. C. U. et al. Ki67 Index , HER2 Status , and Prognosis of Patients With
Luminal B Breast Cancer. J Natl Cancer Inst, v. 101, n. 10, p. 736–750, 2009.
CIRQUEIRA, M. B. et al. Subtipos moleculares do câncer de mama. Femina, v. 39, 2011.
EDGE, S. B.; COMPTON, C. C. The american joint committee on cancer: The 7th edition of
the AJCC cancer staging manual and the future of TNM. Annals of Surgical Oncology, v.
17, n. 6, p. 1471–1474, 2010.
EISENBERG, A. L. A.; KOIFMAN, E S. Câncer de mama: marcadores tumorais. Revista
Brasileira de Cancerologia, p. 337–338, 2001.
EL-HAWARY, A. K. et al. Molecular subtypes of breast carcinoma in Egyptian women:
Clinicopathological features. Pathology Research and Practice, v. 208, n. 7, p. 382–386,
2012.
ELIYATKIN, N. Molecular Classification of Breast Carcinoma: From Traditional, OldFashioned Way to A New Age, and A New Way. J Breast Health, p. 59–66, 2015.
ELKABLAWY, M. A. et al. Molecular profiling of breast carcinoma in Almadinah, KSA:
Immunophenotyping and clinicopathological correlation. Asian Pacific Journal of Cancer
Prevention, v. 16, n. 17, p. 7819–7824, 2015.
FATEMI, H. EL et al. Luminal B tumors are the most frequent molecular subtype in breast
cancer of North African women : an immunohistochemical profile study from Morocco.
Diagnostic Pathology, p. 1–7, 2012.
FOURATI, A. et al. Descriptive analysis of molecular subtypes in Tunisian breast cancer.
Asia-Pacific Journal of Clinical Oncology, v. 10, n. 2, 2012.
FRAGOMENI, S. M.; SCIALLIS, A.; JERUSS, J. S. Molecular Subtypes and Local-Regional
Control of Breast Cancer. Surgical Oncology Clinics of North America, v. 27, n. 1, p. 95–
120, 2018.
GOLDHIRSCH, A. et al. Strategies for subtypes-dealing with the diversity of breast cancer:
Highlights of the St Gallen international expert consensus on the primary therapy of early
breast cancer 2011. Annals of Oncology, v. 22, n. 8, p. 1736–1747, 2011.
HASHMI, A. A. et al. Prognostic parameters of luminal A and luminal B intrinsic breast
cancer subtypes of Pakistani patients. World Journal of Surgical Oncology, v. 16, n. 1, p. 1–
6, 2018.
IARC. Número estimado de casos de incidentes em todo o mundo, mulheres, todas as
idades. Disponível em: <http://gco.iarc.fr/today/online-analysis-multi-bars>. Acesso em: 1
abr. 2021.
IHEMELANDU, C. U.; LEFFALL, L. D.; DEWITTY, R. L. Molecular Breast Cancer
Subtypes in Premenopausal and Postmenopausal African-American Women : Age-Specific
Prevalence and Survival. Journal of Surgical Research, v. 118, p. 109–118, 2007.
KADIVAR, M. et al. Breast cancer molecular subtypes and associations with
clinicopathological characteristics in Iranian women, 2002-2011. Asian Pacific Journal of
Cancer Prevention, v. 13, n. 5, p. 1881–1886, 2012.
LI, J. et al. Clinicopathological classification and traditional prognostic indicators of breast
cancer. International Journal of Clinical and Experimental Pathology, v. 8, n. 7, p. 8500–
8505, 2015.
LONG, Q. et al. Overexpression of lncrna tatdn1 promotes cancer cell proliferation in triple
negative breast cancer by regulating mir-26b methylation. Cancer Management and
Research, v. 12, p. 11403–11410, 2020.
LUNDGREN, C. et al. Agreement between molecular subtyping and surrogate subtype
classification: a contemporary population-based study of ER-positive/HER2-negative primary
breast cancer. Breast Cancer Research and Treatment, v. 178, n. 2, p. 459–467, 2019.
MENDONÇA, G. A. E S.; SILVA, A. M. DA; CAULA, W. M. Características tumorais e
sobrevida de cinco anos em pacientes com câncer de mama admitidas no Instituto Nacional de
Câncer, Rio de Janeiro, Brasil. Cadernos de Saúde Pública, v. 20, n. 5, p. 1232–1239, out.
2004.
MILIOLI, H. H. et al. Basal-like breast cancer : molecular profiles , clinical features and
survival outcomes. BMC Medical Genomics, p. 1–17, 2017.
MUNJAL, K. et al. Immunohistochemical Analysis of ER, PR, Her2 and CK5/6 in Infiltrative
Breast Carcinomas in Indian Patients. Asian Pacific Journal of Cancer Prevention, v. 10, p.
773–778, 2009.
NGUYEN, P. L. et al. Breast cancer subtype approximated by estrogen receptor, progesterone
receptor, and HER-2 is associated with local and distant recurrence after breast-conserving
therapy. Journal of Clinical Oncology, v. 26, n. 14, p. 2373–2378, 2008.
ONITILO, A. A. et al. Breast Cancer Subtypes Based on ER/PR and Her2 Expression:
Comparison of Clinicopathologic Features and Survival. Clinical Medicine & Research, v.
7, n. 1–2, p. 4–13, 2009.
PRAT, A. et al. Molecular Characterization of Basal-Like and Non-Basal-Like TripleNegative Breast Cancer. TheOncologist, p. 123–133, 2013.
RAKHA, E. A. et al. Breast cancer prognostic classification in the molecular era: The role of
histological grade. Breast Cancer Research, v. 12, n. 4, 2010.
RECǍREANU, F. et al. Ductal invasive mammary carcinoma - Clinicopathological
prognostic factors related to immunohistochemical expression of hormonal receptors and
Her2/neu oncoprotein. Romanian Journal of Morphology and Embryology, v. 52, n. 3
SUPPL., p. 1059–1064, 2012.
SALHIA, B. et al. Molecular subtype analysis determines the association of advanced breast
cancer in Egypt with favorable biology. BMC Women’s Health, v. 11, 2011.
SERRA, K. P. et al. Nova classificação dos carcinomas da mama: Procurando o luminal a.
Revista Brasileira de Ginecologia e Obstetricia, v. 36, n. 12, p. 575–580, 2014.
SILVA, P. A. DA; RIUL, S. DA S. Breast cancer: risk factors and early detection. Revista
brasileira de enfermagem, v. 64, n. 6, p. 1016–1021, 2011.
SIMON, R. et al. Pitfalls in the use of DNA microarray data for diagnostic and prognostic
classification. Journal of the National Cancer Institute, v. 95, n. 1, p. 14–18, 2003.
SPITALE, A. et al. Breast cancer classification according to immunohistochemical markers:
Clinicopathologic features and short-term survival analysis in a population-based study from
the South of Switzerland. Annals of Oncology, v. 20, n. 4, p. 628–635, 2009.
STIVAL, R. A. et al. Impacto do fenótipo triplo-negativo no prognóstico de pacientes com
câncer de mama de uma unidade de referência no Brasil central. Rev Bras Mastologia, p. 6–
12, 2012.
VALLEJOS, C. et al. Breast cancer classification according to immunohistochemistry
markers: Subtypes and association with clinicopathologic variables in a peruvian hospital
database. Clinical Breast Cancer, v. 10, n. 4, p. 294–300, 2010.
VIALE, G. The current state of breast cancer classification. Annals of Oncology, v. 23, n.
SUPPL. 10, 2012.
VIEIRA, D. S. C. et al. Carcinoma de mama: Novos conceitos na classificação. Revista
Brasileira de Ginecologia e Obstetricia, v. 30, n. 1, p. 42–47, 2008.
WIECHMANN, L. et al. Presenting features of breast cancer differ by molecular subtype.
Annals of Surgical Oncology, v. 16, n. 10, p. 2705–2710, 2009.
WOLFF, A. C. et al. American Society of Clinical Oncology/College of American
Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing
in breast cancer. Journal of Clinical Oncology, v. 25, n. 1, p. 118–145, 2007.
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2021-07-27
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