CC BY 4.0 · Rev Bras Ginecol Obstet 2023; 45(10): e609-e619
DOI: 10.1055/s-0043-1772183
Review Article

Prognostic Impact of AGR3 Protein Expression in Breast Cancer: A Systematic Review and Meta-analysis

Impacto prognóstico da expressão da proteína AGR3 no câncer de mama: Uma revisão sistemática e metanálise
1   Faculdade de Medicina, Universidade Federal de Goiás, Goiânia, GO, Brazil
2   Faculdade de Medicina, Universidade de Rio Verde, Rio Verde, GO, Brazil
1   Faculdade de Medicina, Universidade Federal de Goiás, Goiânia, GO, Brazil
3   Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil
1   Faculdade de Medicina, Universidade Federal de Goiás, Goiânia, GO, Brazil
2   Faculdade de Medicina, Universidade de Rio Verde, Rio Verde, GO, Brazil
1   Faculdade de Medicina, Universidade Federal de Goiás, Goiânia, GO, Brazil
› Author Affiliations


Objective To investigate the clinicopathological significance and prognosis of the expression of the anterior gradient 3 (AGR3) protein in women with breast cancer.

Data Sources The PubMed, CINAHL, EMBASE, Scopus, and Web of Science databases were searched for studies published in English and without restrictions regarding the year of publication. The search terms were: breast cancer AND anterior gradient 3 OR AGR3 expression.

Study Selection We included observational or interventional studies, studies on AGR3 protein expression by immunohistochemistry, and studies on invasive breast cancer. Case reports, studies with animals, and reviews were excluded. In total, 4 studies were included, containing 713 cases of breast cancer.

Data Collection Data were extracted on clinicopathological characteristics and survival. A meta-analysis of the prevalence of AGR3 expression was performed according to the clinicopathological characteristics, hazard ratios (HRs), and overall survival and disease-free survival.

Data Synthesis The expression of AGR3 was found in 62% of the cases, and it was associated with histological grade II, positivity of estrogen and progesterone receptors, low expression of ki67, recurrence or distant metastasis, and lumen subtypes. In patients with low and intermediate histological grades, AGR3 expression was associated with worse overall survival (HR: 2.39; 95% confidence interval [95%CI]: 0.628–4.159; p = 0.008) and worse disease-free survival (HR: 3.856; 95%CI: 1.026–6.686; p = 0.008).

Conclusion The AGR3 protein may be a biomarker for the early detection of breast cancer and predict prognosis in luminal subtypes. In addition, in patients with low and intermediate histological grades, AGR3 protein expression may indicate an unfavorable prognosis in relation to survival.


Objetivo Investigar o significado clinicopatológico e prognóstico da expressão da proteína anterior gradient 3 (AGR3) em mulheres com câncer de mama.

Fontes de Dados Utilizamos as bases de dados PubMed, CINAHL, EMBASE, Scopus e Web of Science para pesquisar estudos em inglês, sem restrições quanto ao ano de publicação. Os termos buscados foram: breast cancer AND anterior gradient 3 OR AGR3 expression.

Seleção dos Estudos Foram incluídos estudos observacionais ou intervencionais, estudos sobre a expressão da proteína AGR3 por imuno-histoquímica, e estudos sobre câncer de mama invasivo. Excluíram-se relatos de casos, estudos com animais e revisões. Quatro estudos foram selecionados, que continham 713 casos de câncer de mama.

Coleta de Dados Foram extraídos dados relativos a características clinicopatológicas e sobrevida. A metanálise da prevalência da expressão de AGR3 foi realizada conforme as características clinicopatológicas, razões de risco (RRs) e sobrevida global (SG) e sobrevida livre de doença (SLD).

Síntese dos Dados Encontrou-se expressão de AGR3 em 62% dos casos, que se associou com grau histológico II, positividade de receptores de estrogênio e progesterona, baixa expressão de ki67, recorrência ou metástase à distância e subtipos luminais. Em pacientes com graus histológicos baixo e intermediário, a expressão de AGR3 conferiu pior SG (RR: 2,39; intervalo de confiança de 95% [IC95%]: 0,628–4,159; p = 0,008) e pior SLD (RR: 3,856; IC95%: 1,026–6,686; p = 0,008).

Conclusão A AGR3 pode ser um biomarcador para a detecção precoce do câncer de mama e predizer o prognóstico em subtipos luminais. Em graus histológicos baixo e intermediário, a expressão da proteína AGR3 pode indicar um prognóstico desfavorável em relação à sobrevida.

Publication History

Received: 22 November 2022

Accepted: 21 March 2023

Article published online:
09 November 2023

© 2023. Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (

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