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Doctoral Thesis
DOI
https://doi.org/10.11606/T.17.2021.tde-11062021-083252
Document
Author
Full name
Leonardo Fleury Orlandini
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2021
Supervisor
Committee
Tiezzi, Daniel Guimarães (President)
Carrara, Helio Humberto Angotti
Freitas Junior, Ruffo de
Pessoa, Eduardo Carvalho
Title in Portuguese
Associação entre câncer de mama e obesidade, e influência de dois biomarcadores inflamatórios no prognóstico de câncer de mama nesta população, a relação neutrófilo/linfócito e plaquetas/linfócitos
Keywords in Portuguese
Câncer de mama
Índice de massa corporal
Obesidade
Relação neutrófilos/linfócitos
Relação plaquetas/linfócitos
Abstract in Portuguese
Obesidade tem sido associada a um aumento de risco para desenvolvimento de câncer de mama, além de maior recorrência e mortalidade por esta neoplasia. Alguns biomarcadores séricos associados a inflamação sistêmica, por serem de baixo custo e fácil aquisição, têm sido estudados como fatores prognóstico em pacientes com câncer, entre eles a relação neutrófilo/linfócito (NLR) e a relação plaquetas/linfócitos (PLR). Este estudo tem como objetivo avaliar a associação entre o índice de massa corporal (IMC) e câncer de mama, e a influência do NLR e PLR no prognóstico dessas pacientes em uma coorte de mulheres brasileiras com longo tempo de seguimento. Trata-se de análise retrospectiva dos registros das pacientes atendidas e tratadas por câncer de mama no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (USP) no período entre 1999 e 2013. Foram utilizados os dados clínicos e patológicos coletados antes do primeiro tratamento. Para análise de sobrevida foram realizados modelos de regressão de Cox. Das 1.831 pacientes incluídas, 620 (33,8%) eram obesas na ocasião do diagnóstico (BMI≥30kg/m2). Obesas tinham tumores maiores comparadas as não-obesas (mediana 22mm versus 20mm, p=0.01). IMC acima de 30 foi associado a pior sobrevida livre de doença e maior mortalidade apenas em pacientes com doença inicial (estádio I), mas não em doença mais avançada. Valores elevados de NLR foram fator prognóstico independentes de maior recorrência e mortalidade. Um subgrupo de pacientes com alto NLR e alto IMC tiveram piores recorrência (p=0.046, logrank), sobrevida específica (p<0.001, log-rank) e global (p=0.006, log-rank) entre as demais. A PLR elevada não se mostrou um fator prognóstico independente para câncer de mama na análise multivariada. Em conclusão, nós encontramos um efeito negativo da obesidade apenas em pacientes com câncer de mama estádio I, uma parcela de pacientes que geralmente apresentam bom prognóstico. Adicionalmente, NLR elevado foi considerado um fator prognóstico independente para pior sobrevida em 10 anos, principalmente em um subgrupo de mulheres com alto NLR e obesidade.
Title in English
Body mass index and breast cancer, and the association with two inflammatory biomarkers, the neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio
Keywords in English
Body mass index
Breast cancer
Neutrophil-to-lymphocyte ratio
Obesity
Platelet-to-lymphocyte ratio
Abstract in English
Obesity has been associated with an increased risk of breast cancer recurrence and death. Some readily available biomarkers associated with obesity and chronic systemic inflammation have been receiving attention as potential prognostic indicators of cancer, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). This study aimed to explore the correlation between body mass index (BMI) and NLR and PLR in invasive breast cancer patients. We further investigated the association of NLR, PLR and BMI with breast cancer recurrence and survival in a long-term follow-up cohort. Retrospective analysis of patients treated for breast cancer at a Brazilian hospital between 1999 and 2013 was performed. Clinicopathological data was obtained before the first treatment. Cox regression models were used for survival analyses. Of the 1,831 patients included, 620 (33,8%) were obese (BMI ≥ 30kg/m2). Obese women had larger tumors compared to non-obese women (median 22mm versus 20mm, p=0.01). Higher BMI was associated with worse overall survival and disease-free survival (DFS) in women with Stage I disease, but not in the more advanced stages. Higher NLR was found to be an independent prognostic factor for recurrence and mortality. A subgroup of patients with high NLR and high BMI had the worst DFS (p=0.046, log-rank), breast cancer specific survival (p<0.001, log-rank) and overall survival (p=0.006, log-rank), compared to the other groups. The PLR was not an independent prognostic factor in multivariate analysis. In conclusion, we found a negative impact of obesity only in stage I disease, a subgroup of patients with generally favorable prognostic features. Additionally, high NLR was found to be an independent prognostic factor for worse survival and recurrence of breast cancer, particularly, in a subgroup of women with high NLR and obesity.
 
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Publishing Date
2021-06-18
 
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