Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy

Autores
Nadin, Silvina Beatriz; Sottile Fleury, Mayra Lis; Montt Guevara, Maria Magdalena; Gauna, Gisel Valeria; Daguerre, Pedro; Leuzzi, Marcela; Gago, Francisco E.; Ibarra, Jorge; Cuello Carrión, Fernando Darío; Ciocca, Daniel Ramon; Vargas Roig, Laura Maria
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to reduce the tumor size before surgery. Unfortunately, resistance to chemotherapy may arise from a variety of mechanisms. The heat shock proteins (HSPs), which are highly expressed in mammary tumor cells, have been implicated in anticancer drug resistance. In spite of the widely described value of HSPs as molecular markers in cancer, their implications in breast tumors treated with anthracycline-based neoadjuvant chemotherapy has been poorly explored. In this study, we have evaluated by immunohistochemistry the expression of HSP27 (HSPB1) and HSP70 (HSPA) in serial biopsies from locally advanced breast cancer patients (n= 60) treated with doxorubicin (DOX) or epirubicin (EPI) based monochemotherapy. The serial biopsies were taken at days 1, 3, 7, 21, and compared with the pre-chemotherapy and the surgical biopsies. After surgery the patients received additional chemotherapy with Cyclophosphamide, Methotrexate and 5-Fluorouracil (CMF). High nuclear HSPB1 and HSPA expressions were found in invasive cells after DOX/EPI administration (P<0.001), but the drug did not affect the cytoplasmic expression of the HSPs. Infiltrating lymphocytes showed high nuclear HSPA (P<0.01) levels at post-chemotherapy. No correlations were found between HSPs expression and the clinical and pathological response to neoadjuvant therapy. However, in the post-chemotherapy biopsies, high nuclear (>31% of the cells) and cytoplasmic HSPA expressions (>11% of the tumor cells) were associated with better DFS (P=0.0348 and P=0.0118, respectively). We conclude that HSPA expression may be a useful prognostic marker in breast cancer patients treated with neoadjuvant DOX/EPI chemotherapy, indicating the need to change the administered drugs after surgery for overcoming drug resistance.
Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Gauna, Gisel Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Daguerre, Pedro. Hospital Luis Lagomaggiore; Argentina
Fil: Leuzzi, Marcela. Hospital Luis Lagomaggiore; Argentina
Fil: Gago, Francisco E.. Universidad Nacional de Cuyo; Argentina
Fil: Ibarra, Jorge. Hospital Luis Lagomaggiore; Argentina
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Materia
Breast Cancer
Neoadjuvant Chemotherapy
Anthracyclines
Heat Shock Proteins
Prognostic Factors
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/32014
Acceder
id CONICETDig_aec2673c55895205594e18d3129217a8
oai_identifier_str oai:ri.conicet.gov.ar:11336/32014
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapyNadin, Silvina BeatrizSottile Fleury, Mayra LisMontt Guevara, Maria MagdalenaGauna, Gisel ValeriaDaguerre, PedroLeuzzi, MarcelaGago, Francisco E.Ibarra, JorgeCuello Carrión, Fernando DaríoCiocca, Daniel RamonVargas Roig, Laura MariaBreast CancerNeoadjuvant ChemotherapyAnthracyclinesHeat Shock ProteinsPrognostic Factorshttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to reduce the tumor size before surgery. Unfortunately, resistance to chemotherapy may arise from a variety of mechanisms. The heat shock proteins (HSPs), which are highly expressed in mammary tumor cells, have been implicated in anticancer drug resistance. In spite of the widely described value of HSPs as molecular markers in cancer, their implications in breast tumors treated with anthracycline-based neoadjuvant chemotherapy has been poorly explored. In this study, we have evaluated by immunohistochemistry the expression of HSP27 (HSPB1) and HSP70 (HSPA) in serial biopsies from locally advanced breast cancer patients (n= 60) treated with doxorubicin (DOX) or epirubicin (EPI) based monochemotherapy. The serial biopsies were taken at days 1, 3, 7, 21, and compared with the pre-chemotherapy and the surgical biopsies. After surgery the patients received additional chemotherapy with Cyclophosphamide, Methotrexate and 5-Fluorouracil (CMF). High nuclear HSPB1 and HSPA expressions were found in invasive cells after DOX/EPI administration (P<0.001), but the drug did not affect the cytoplasmic expression of the HSPs. Infiltrating lymphocytes showed high nuclear HSPA (P<0.01) levels at post-chemotherapy. No correlations were found between HSPs expression and the clinical and pathological response to neoadjuvant therapy. However, in the post-chemotherapy biopsies, high nuclear (>31% of the cells) and cytoplasmic HSPA expressions (>11% of the tumor cells) were associated with better DFS (P=0.0348 and P=0.0118, respectively). We conclude that HSPA expression may be a useful prognostic marker in breast cancer patients treated with neoadjuvant DOX/EPI chemotherapy, indicating the need to change the administered drugs after surgery for overcoming drug resistance.Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Gauna, Gisel Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Daguerre, Pedro. Hospital Luis Lagomaggiore; ArgentinaFil: Leuzzi, Marcela. Hospital Luis Lagomaggiore; ArgentinaFil: Gago, Francisco E.. Universidad Nacional de Cuyo; ArgentinaFil: Ibarra, Jorge. Hospital Luis Lagomaggiore; ArgentinaFil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaSpringer2013-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/32014Nadin, Silvina Beatriz; Sottile Fleury, Mayra Lis; Montt Guevara, Maria Magdalena; Gauna, Gisel Valeria; Daguerre, Pedro; et al.; Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy; Springer; Cell Stress & Chaperones; 19; 4; 12-2013; 493-5051355-81451466-1268CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s12192-013-0475-2info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs12192-013-0475-2info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:48Zoai:ri.conicet.gov.ar:11336/32014instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:55:48.539CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy
title Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy
spellingShingle Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy
Nadin, Silvina Beatriz
Breast Cancer
Neoadjuvant Chemotherapy
Anthracyclines
Heat Shock Proteins
Prognostic Factors
title_short Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy
title_full Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy
title_fullStr Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy
title_full_unstemmed Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy
title_sort Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy
dc.creator.none.fl_str_mv Nadin, Silvina Beatriz
Sottile Fleury, Mayra Lis
Montt Guevara, Maria Magdalena
Gauna, Gisel Valeria
Daguerre, Pedro
Leuzzi, Marcela
Gago, Francisco E.
Ibarra, Jorge
Cuello Carrión, Fernando Darío
Ciocca, Daniel Ramon
Vargas Roig, Laura Maria
author Nadin, Silvina Beatriz
author_facet Nadin, Silvina Beatriz
Sottile Fleury, Mayra Lis
Montt Guevara, Maria Magdalena
Gauna, Gisel Valeria
Daguerre, Pedro
Leuzzi, Marcela
Gago, Francisco E.
Ibarra, Jorge
Cuello Carrión, Fernando Darío
Ciocca, Daniel Ramon
Vargas Roig, Laura Maria
author_role author
author2 Sottile Fleury, Mayra Lis
Montt Guevara, Maria Magdalena
Gauna, Gisel Valeria
Daguerre, Pedro
Leuzzi, Marcela
Gago, Francisco E.
Ibarra, Jorge
Cuello Carrión, Fernando Darío
Ciocca, Daniel Ramon
Vargas Roig, Laura Maria
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Breast Cancer
Neoadjuvant Chemotherapy
Anthracyclines
Heat Shock Proteins
Prognostic Factors
topic Breast Cancer
Neoadjuvant Chemotherapy
Anthracyclines
Heat Shock Proteins
Prognostic Factors
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to reduce the tumor size before surgery. Unfortunately, resistance to chemotherapy may arise from a variety of mechanisms. The heat shock proteins (HSPs), which are highly expressed in mammary tumor cells, have been implicated in anticancer drug resistance. In spite of the widely described value of HSPs as molecular markers in cancer, their implications in breast tumors treated with anthracycline-based neoadjuvant chemotherapy has been poorly explored. In this study, we have evaluated by immunohistochemistry the expression of HSP27 (HSPB1) and HSP70 (HSPA) in serial biopsies from locally advanced breast cancer patients (n= 60) treated with doxorubicin (DOX) or epirubicin (EPI) based monochemotherapy. The serial biopsies were taken at days 1, 3, 7, 21, and compared with the pre-chemotherapy and the surgical biopsies. After surgery the patients received additional chemotherapy with Cyclophosphamide, Methotrexate and 5-Fluorouracil (CMF). High nuclear HSPB1 and HSPA expressions were found in invasive cells after DOX/EPI administration (P<0.001), but the drug did not affect the cytoplasmic expression of the HSPs. Infiltrating lymphocytes showed high nuclear HSPA (P<0.01) levels at post-chemotherapy. No correlations were found between HSPs expression and the clinical and pathological response to neoadjuvant therapy. However, in the post-chemotherapy biopsies, high nuclear (>31% of the cells) and cytoplasmic HSPA expressions (>11% of the tumor cells) were associated with better DFS (P=0.0348 and P=0.0118, respectively). We conclude that HSPA expression may be a useful prognostic marker in breast cancer patients treated with neoadjuvant DOX/EPI chemotherapy, indicating the need to change the administered drugs after surgery for overcoming drug resistance.
Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Gauna, Gisel Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Daguerre, Pedro. Hospital Luis Lagomaggiore; Argentina
Fil: Leuzzi, Marcela. Hospital Luis Lagomaggiore; Argentina
Fil: Gago, Francisco E.. Universidad Nacional de Cuyo; Argentina
Fil: Ibarra, Jorge. Hospital Luis Lagomaggiore; Argentina
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
description Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to reduce the tumor size before surgery. Unfortunately, resistance to chemotherapy may arise from a variety of mechanisms. The heat shock proteins (HSPs), which are highly expressed in mammary tumor cells, have been implicated in anticancer drug resistance. In spite of the widely described value of HSPs as molecular markers in cancer, their implications in breast tumors treated with anthracycline-based neoadjuvant chemotherapy has been poorly explored. In this study, we have evaluated by immunohistochemistry the expression of HSP27 (HSPB1) and HSP70 (HSPA) in serial biopsies from locally advanced breast cancer patients (n= 60) treated with doxorubicin (DOX) or epirubicin (EPI) based monochemotherapy. The serial biopsies were taken at days 1, 3, 7, 21, and compared with the pre-chemotherapy and the surgical biopsies. After surgery the patients received additional chemotherapy with Cyclophosphamide, Methotrexate and 5-Fluorouracil (CMF). High nuclear HSPB1 and HSPA expressions were found in invasive cells after DOX/EPI administration (P<0.001), but the drug did not affect the cytoplasmic expression of the HSPs. Infiltrating lymphocytes showed high nuclear HSPA (P<0.01) levels at post-chemotherapy. No correlations were found between HSPs expression and the clinical and pathological response to neoadjuvant therapy. However, in the post-chemotherapy biopsies, high nuclear (>31% of the cells) and cytoplasmic HSPA expressions (>11% of the tumor cells) were associated with better DFS (P=0.0348 and P=0.0118, respectively). We conclude that HSPA expression may be a useful prognostic marker in breast cancer patients treated with neoadjuvant DOX/EPI chemotherapy, indicating the need to change the administered drugs after surgery for overcoming drug resistance.
publishDate 2013
dc.date.none.fl_str_mv 2013-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/32014
Nadin, Silvina Beatriz; Sottile Fleury, Mayra Lis; Montt Guevara, Maria Magdalena; Gauna, Gisel Valeria; Daguerre, Pedro; et al.; Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy; Springer; Cell Stress & Chaperones; 19; 4; 12-2013; 493-505
1355-8145
1466-1268
CONICET Digital
CONICET
url http://hdl.handle.net/11336/32014
identifier_str_mv Nadin, Silvina Beatriz; Sottile Fleury, Mayra Lis; Montt Guevara, Maria Magdalena; Gauna, Gisel Valeria; Daguerre, Pedro; et al.; Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy; Springer; Cell Stress & Chaperones; 19; 4; 12-2013; 493-505
1355-8145
1466-1268
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs12192-013-0475-2
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
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reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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