Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozol

Detalhes bibliográficos
Autor(a) principal: Melitto, Alexandre Santos [UNIFESP]
Data de Publicação: 2009
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UNIFESP
dARK ID: ark:/48912/0013000013qs6
Texto Completo: http://repositorio.unifesp.br/handle/11600/9558
Resumo: Background: Frequent deletions or mutations of the INK4 gene, which encodes the cyclin-dependent kinase 4 inhibitor p16INK4a, have been documented in various human cancers, but little is known about the role of this tumor suppressor gene in primary breast cancer and there is a lack in the literature about its expression behavior in neoadjuvant endocrinetherapy with tamoxifen or anastrozole. Objective: Analysis of p16INK4a expression in patients with invasive ductal carcinomas (IDC) prior to tamoxifen and anastrozole neoadjuvant treatment and possible correlation between predictive and prognostical factors – estrogen receptor (ER), progesterone receptor (PgR). Methods: We examined p16INK4a mRNA expression and its relationship with short period (26 days) neoadjuvant endocrine therapy with tamoxifen and anastrozole in 58 primary breast cancers with palpable ER-positive IDC. They were double-blind randomized in three neoadjuvant treatment groups for 21 days: Anastrozole 1mg/day (n= 17), Placebo (n=25) and Tamoxifen 20mg/day (n=15). Biomarkers status (ER, PgR and p16) were obtained by comparing single immunohistochemical evaluation of pre and post-surgery samples using Allred’s method. Statistical analyses were performed using the SPSS software for Windows. Results: Variation in p16 was 22% to 17% in anastrozole group, 8% to 4% in placebo group and there was no variation in tamoxifen group, standing in 7%. There was no significant statistical diference in p16INK4a expression among the three groups (p=0.17). Variation in p16 was 12% to 9% (p<0.05) when considering the three groups together. There was a significant decrease of p16 expression in pre and post surgery results. There was no significant statistical correlation between p16 expression and hormonal status (RE and RP). Conclusions: There was no significant statistical diference in p16INK4a expression among the three groups. There was a significant statistical decrease in p16INK4a expression when compared pre and post surgery values. These findings could indicate that expression of p16 and variation in pre and post surgery samples are associated with hormone responsiveness and mechanisms of resistance. There were no significant statistical correlation between p16 expression and hormonal status (RE and RP). Further studies are necessary to understand their functional interrelationships and whether high p16INK4a expression may be associated with a lack of hormone responsiveness in breast cancer.
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spelling Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozolExpression of p16 in short term exposition with tamoxifen and anastrozole in postmenopausal women with breast invasive cancerAnastrozolCâncer de mamaHormonioterapiaBiomarcador p16TamoxifenoAnastrozolePostmenopausal womenTamoxifenBreast cancerBackground: Frequent deletions or mutations of the INK4 gene, which encodes the cyclin-dependent kinase 4 inhibitor p16INK4a, have been documented in various human cancers, but little is known about the role of this tumor suppressor gene in primary breast cancer and there is a lack in the literature about its expression behavior in neoadjuvant endocrinetherapy with tamoxifen or anastrozole. Objective: Analysis of p16INK4a expression in patients with invasive ductal carcinomas (IDC) prior to tamoxifen and anastrozole neoadjuvant treatment and possible correlation between predictive and prognostical factors – estrogen receptor (ER), progesterone receptor (PgR). Methods: We examined p16INK4a mRNA expression and its relationship with short period (26 days) neoadjuvant endocrine therapy with tamoxifen and anastrozole in 58 primary breast cancers with palpable ER-positive IDC. They were double-blind randomized in three neoadjuvant treatment groups for 21 days: Anastrozole 1mg/day (n= 17), Placebo (n=25) and Tamoxifen 20mg/day (n=15). Biomarkers status (ER, PgR and p16) were obtained by comparing single immunohistochemical evaluation of pre and post-surgery samples using Allred’s method. Statistical analyses were performed using the SPSS software for Windows. Results: Variation in p16 was 22% to 17% in anastrozole group, 8% to 4% in placebo group and there was no variation in tamoxifen group, standing in 7%. There was no significant statistical diference in p16INK4a expression among the three groups (p=0.17). Variation in p16 was 12% to 9% (p<0.05) when considering the three groups together. There was a significant decrease of p16 expression in pre and post surgery results. There was no significant statistical correlation between p16 expression and hormonal status (RE and RP). Conclusions: There was no significant statistical diference in p16INK4a expression among the three groups. There was a significant statistical decrease in p16INK4a expression when compared pre and post surgery values. These findings could indicate that expression of p16 and variation in pre and post surgery samples are associated with hormone responsiveness and mechanisms of resistance. There were no significant statistical correlation between p16 expression and hormonal status (RE and RP). Further studies are necessary to understand their functional interrelationships and whether high p16INK4a expression may be associated with a lack of hormone responsiveness in breast cancer.Introdução: A endocrinoterapia é uma das principais responsáveis pela redução de mortalidade do câncer de mama. Biomarcadores preditivos de resposta celular precoce vêm sendo estudados com intuito de prever precocemente a hormonioresistência. Freqüentes deleções e mutações têm sido descritas no gene p16 em diversos tipos de tumores, mas pouco se sabe sobre seu papel no câncer de mama e seu comportamento após endocrinoterapia neoadjuvante com tamoxifeno e anastrozol. Objetivos: Estudar a expressão do p16 e dos receptores de estrogênio e progesterona (RE e RP) em pacientes na pós - menopausa com carcinoma de mama RE e/ ou RP (+) após curto período (26 dias) de tratamento com tamoxifeno, anastrozol e placebo. Métodos: Estudo prospectivo randomizado duplo-cego realizado com 58 pacientes dos Hospitais Pérola Byington e São Paulo da UNIFESP (São Paulo - Brasil) com carcinoma ductal infiltrativo de mama, nos estádios II e III, que no período pré-operatório foram subdivididas em três grupos: P (placebo, N=25), T (tamoxifeno 20mg/dia, N=15) e A (anastrozol 1mg/dia, N=18). A biópsia foi realizada no momento do diagnóstico e após a cirurgia definitiva (26º dia) e os tumores foram isolados por micro-arranjos teciduais. O estudo imunoistoquímico foi realizado com anticorpos para p16 (Dako- OA315), RE (Neomarkers-M7047), RP (Dako- M3569). Realizou-se o estudo semiquantitativo utilizando-se os critérios de Allred e o estudo estatístico pelo teste paramétrico de Anova. Resultados: A positividade do p16 variou de 22 para 17%, respectivamente pré e pós tratamento com anastrozol; de 8 para 4% no grupo placebo e não houve variação, com 7% de positividade, no grupo que recebeu tamoxifeno. A comparação entre grupos e tempos não apresentou relação significativa para o p16 (p=0,17). Não foi encontrada correlação entre a positividade do p16 e o status hormonal (RE e RP). Conclusão: Não houve diferença estatística significante entre os três grupos estudados. Futuros estudos com métodos moleculares poderão esclarecer dúvidas suscitadas a respeito do tempo de exposição à droga necessária para interferir nos biomarcadores e proteínas.TEDEBV UNIFESP: Teses e dissertaçõesUniversidade Federal de São Paulo (UNIFESP)Gebrim, Luiz Henrique [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Melitto, Alexandre Santos [UNIFESP]2015-07-22T20:50:08Z2015-07-22T20:50:08Z2009-11-25info:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/publishedVersion92 p.application/pdfMELITTO, Alexandre Santos. Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozol. 2009. Dissertação (Mestrado) - Universidade Federal de São Paulo (UNIFESP), São Paulo, 2009.Restrito-11912.pdfepm-0070715443343.pdfPublico-9558.pdfhttp://repositorio.unifesp.br/handle/11600/9558ark:/48912/0013000013qs6porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-07-29T09:03:16Zoai:repositorio.unifesp.br/:11600/9558Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:54:03.754829Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozol
Expression of p16 in short term exposition with tamoxifen and anastrozole in postmenopausal women with breast invasive cancer
title Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozol
spellingShingle Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozol
Melitto, Alexandre Santos [UNIFESP]
Anastrozol
Câncer de mama
Hormonioterapia
Biomarcador p16
Tamoxifeno
Anastrozole
Postmenopausal women
Tamoxifen
Breast cancer
title_short Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozol
title_full Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozol
title_fullStr Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozol
title_full_unstemmed Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozol
title_sort Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozol
author Melitto, Alexandre Santos [UNIFESP]
author_facet Melitto, Alexandre Santos [UNIFESP]
author_role author
dc.contributor.none.fl_str_mv Gebrim, Luiz Henrique [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Melitto, Alexandre Santos [UNIFESP]
dc.subject.por.fl_str_mv Anastrozol
Câncer de mama
Hormonioterapia
Biomarcador p16
Tamoxifeno
Anastrozole
Postmenopausal women
Tamoxifen
Breast cancer
topic Anastrozol
Câncer de mama
Hormonioterapia
Biomarcador p16
Tamoxifeno
Anastrozole
Postmenopausal women
Tamoxifen
Breast cancer
description Background: Frequent deletions or mutations of the INK4 gene, which encodes the cyclin-dependent kinase 4 inhibitor p16INK4a, have been documented in various human cancers, but little is known about the role of this tumor suppressor gene in primary breast cancer and there is a lack in the literature about its expression behavior in neoadjuvant endocrinetherapy with tamoxifen or anastrozole. Objective: Analysis of p16INK4a expression in patients with invasive ductal carcinomas (IDC) prior to tamoxifen and anastrozole neoadjuvant treatment and possible correlation between predictive and prognostical factors – estrogen receptor (ER), progesterone receptor (PgR). Methods: We examined p16INK4a mRNA expression and its relationship with short period (26 days) neoadjuvant endocrine therapy with tamoxifen and anastrozole in 58 primary breast cancers with palpable ER-positive IDC. They were double-blind randomized in three neoadjuvant treatment groups for 21 days: Anastrozole 1mg/day (n= 17), Placebo (n=25) and Tamoxifen 20mg/day (n=15). Biomarkers status (ER, PgR and p16) were obtained by comparing single immunohistochemical evaluation of pre and post-surgery samples using Allred’s method. Statistical analyses were performed using the SPSS software for Windows. Results: Variation in p16 was 22% to 17% in anastrozole group, 8% to 4% in placebo group and there was no variation in tamoxifen group, standing in 7%. There was no significant statistical diference in p16INK4a expression among the three groups (p=0.17). Variation in p16 was 12% to 9% (p<0.05) when considering the three groups together. There was a significant decrease of p16 expression in pre and post surgery results. There was no significant statistical correlation between p16 expression and hormonal status (RE and RP). Conclusions: There was no significant statistical diference in p16INK4a expression among the three groups. There was a significant statistical decrease in p16INK4a expression when compared pre and post surgery values. These findings could indicate that expression of p16 and variation in pre and post surgery samples are associated with hormone responsiveness and mechanisms of resistance. There were no significant statistical correlation between p16 expression and hormonal status (RE and RP). Further studies are necessary to understand their functional interrelationships and whether high p16INK4a expression may be associated with a lack of hormone responsiveness in breast cancer.
publishDate 2009
dc.date.none.fl_str_mv 2009-11-25
2015-07-22T20:50:08Z
2015-07-22T20:50:08Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv MELITTO, Alexandre Santos. Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozol. 2009. Dissertação (Mestrado) - Universidade Federal de São Paulo (UNIFESP), São Paulo, 2009.
Restrito-11912.pdf
epm-0070715443343.pdf
Publico-9558.pdf
http://repositorio.unifesp.br/handle/11600/9558
dc.identifier.dark.fl_str_mv ark:/48912/0013000013qs6
identifier_str_mv MELITTO, Alexandre Santos. Estudo do biomarcador p16 no carcinoma de mama de mulheres submetidas à endocrinoterapia primária de curta duração com tamoxifeno e anastrozol. 2009. Dissertação (Mestrado) - Universidade Federal de São Paulo (UNIFESP), São Paulo, 2009.
Restrito-11912.pdf
epm-0070715443343.pdf
Publico-9558.pdf
ark:/48912/0013000013qs6
url http://repositorio.unifesp.br/handle/11600/9558
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 92 p.
application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
publisher.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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