Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer

Priscilla Merriam, William M Sikov Department of Medicine, Division of Hematology-Oncology, Warren Alpert Medical School of Brown University, Providence, RI, USA Abstract: Breast cancers that overexpress human epidermal growth factor receptor-2 (HER2-positive [HER2+]) tend to be biologically aggress...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Merriam PA, Sikov WM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/646f694eac0b4fcfa9bd6d9090aaaa75
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:646f694eac0b4fcfa9bd6d9090aaaa75
record_format	dspace
spelling	oai:doaj.org-article:646f694eac0b4fcfa9bd6d9090aaaa752021-12-02T06:29:56ZClinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer1179-1314https://doaj.org/article/646f694eac0b4fcfa9bd6d9090aaaa752011-10-01T00:00:00Zhttp://www.dovepress.com/clinical-utility-of-the-combination-of-lapatinib-and-letrozole-in-the--a8541https://doaj.org/toc/1179-1314Priscilla Merriam, William M Sikov Department of Medicine, Division of Hematology-Oncology, Warren Alpert Medical School of Brown University, Providence, RI, USA Abstract: Breast cancers that overexpress human epidermal growth factor receptor-2 (HER2-positive [HER2+]) tend to be biologically aggressive and associated with a poor prognosis, even those that coexpress receptors for estrogen and/or progesterone (hormone receptor-positive [HR+]). Optimal therapy for patients with &ldquo;double-positive&rdquo; (HR+/HER2+) breast cancers is still being defined. In this subset of patients, the efficacy of targeted endocrine therapies appears to be diminished by cross-activation or &ldquo;crosstalk&rdquo; between estrogen receptor-mediated gene transcription and pathways activated by other growth factor receptors, including HER2. Lapatinib is a tyrosine kinase inhibitor which binds reversibly to the intracellular domains of the epidermal growth factor receptor and HER2, interfering with their ability to initiate signal transduction cascades that promote cancer cell proliferation, survival, and metastasis. In a recently published randomized, placebo-controlled Phase III study in postmenopausal HR+ metastatic breast cancer, the addition of lapatinib to the aromatase inhibitor letrozole significantly improved progression-free survival solely in women who were also HER2+. This article reviews the biology of &ldquo;double-positive&rdquo; breast cancers and the rationale underlying combining endocrine and HER2-targeted therapies, including the lapatinib/letrozole combination, for these tumors. Results from the Phase III trial are examined, as well as available data on other combinations of HR and HER2-targeted therapies. Ongoing trials and potential future applications of these combinations in both HR+/HER2+ and other subgroups of breast cancer patients are also discussed. Keywords: breast neoplasm, erbB2, estrogen receptor, letrozole, lapatinibMerriam PASikov WMDove Medical PressarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol 2011, Iss default, Pp 139-150 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Merriam PA Sikov WM Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer
description	Priscilla Merriam, William M Sikov Department of Medicine, Division of Hematology-Oncology, Warren Alpert Medical School of Brown University, Providence, RI, USA Abstract: Breast cancers that overexpress human epidermal growth factor receptor-2 (HER2-positive [HER2+]) tend to be biologically aggressive and associated with a poor prognosis, even those that coexpress receptors for estrogen and/or progesterone (hormone receptor-positive [HR+]). Optimal therapy for patients with &ldquo;double-positive&rdquo; (HR+/HER2+) breast cancers is still being defined. In this subset of patients, the efficacy of targeted endocrine therapies appears to be diminished by cross-activation or &ldquo;crosstalk&rdquo; between estrogen receptor-mediated gene transcription and pathways activated by other growth factor receptors, including HER2. Lapatinib is a tyrosine kinase inhibitor which binds reversibly to the intracellular domains of the epidermal growth factor receptor and HER2, interfering with their ability to initiate signal transduction cascades that promote cancer cell proliferation, survival, and metastasis. In a recently published randomized, placebo-controlled Phase III study in postmenopausal HR+ metastatic breast cancer, the addition of lapatinib to the aromatase inhibitor letrozole significantly improved progression-free survival solely in women who were also HER2+. This article reviews the biology of &ldquo;double-positive&rdquo; breast cancers and the rationale underlying combining endocrine and HER2-targeted therapies, including the lapatinib/letrozole combination, for these tumors. Results from the Phase III trial are examined, as well as available data on other combinations of HR and HER2-targeted therapies. Ongoing trials and potential future applications of these combinations in both HR+/HER2+ and other subgroups of breast cancer patients are also discussed. Keywords: breast neoplasm, erbB2, estrogen receptor, letrozole, lapatinib
format	article
author	Merriam PA Sikov WM
author_facet	Merriam PA Sikov WM
author_sort	Merriam PA
title	Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer
title_short	Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer
title_full	Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer
title_fullStr	Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer
title_full_unstemmed	Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer
title_sort	clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and her2-positive advanced breast cancer
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/646f694eac0b4fcfa9bd6d9090aaaa75
work_keys_str_mv	AT merriampa clinicalutilityofthecombinationoflapatinibandletrozoleinthemanagementofhormonereceptorpositiveandher2positiveadvancedbreastcancer AT sikovwm clinicalutilityofthecombinationoflapatinibandletrozoleinthemanagementofhormonereceptorpositiveandher2positiveadvancedbreastcancer
_version_	1718399873659699200

Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer

Ejemplares similares