PI3K mutations in breast cancer: prognostic and therapeutic implications

Toru MukoharaCancer Center and Division of Medical Oncology/Hematology, Kobe University Hospital, Kobe, JapanAbstract: The PI3K pathway is the most frequently enhanced oncogenic pathway in breast cancer. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (~30%) observed, alon...

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Autor principal:	Mukohara T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/3fd2933d14fe461bb213d49ef70aed6c
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spelling	oai:doaj.org-article:3fd2933d14fe461bb213d49ef70aed6c2021-12-02T01:23:12ZPI3K mutations in breast cancer: prognostic and therapeutic implications1179-1314https://doaj.org/article/3fd2933d14fe461bb213d49ef70aed6c2015-05-01T00:00:00Zhttp://www.dovepress.com/pi3k-mutations-in-breast-cancer-prognostic-and-therapeutic-implication-peer-reviewed-article-BCTThttps://doaj.org/toc/1179-1314Toru MukoharaCancer Center and Division of Medical Oncology/Hematology, Kobe University Hospital, Kobe, JapanAbstract: The PI3K pathway is the most frequently enhanced oncogenic pathway in breast cancer. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (~30%) observed, along with protein loss of PTEN. Since the first discovery of PIK3CA mutations in solid malignancies in 2004, numerous studies have revealed the prognostic and therapeutic implications of these mutations. Although many issues remain unconfirmed, some have been carved in stone by the level of consistency they have shown among studies: 1) PIK3CA mutations are most likely to be observed in ER-positive/HER2-negative tumors, and are associated with other good prognostic characters; 2) PIK3CA mutations can coexist with other PI3K-enhancing mechanisms, such as HER2 amplification and PTEN protein loss; 3) PIK3CA mutations are potentially a good prognostic marker; 4) PIK3CA may predict a poorer tumor response to trastuzumab-based therapies, but its impact on disease-free survival and overall survival is uncertain; and 5) based on reports of early clinical trials, PIK3CA mutations do not guarantee a dramatic response to PI3K inhibitors. Collectively, there is currently no sufficient evidence to recommend routine genotyping of PIK3CA in clinical practice. Given that PIK3CA-mutant breast cancer appears to have a distinct tumor biology, development of more individualized targeted therapies based on the PIK3CA genotype is awaited.Keywords: PI3K, PIK3CA, prognostic factor, predictive factor, trastuzumabMukohara TDove Medical PressarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol 2015, Iss default, Pp 111-123 (2015)
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 Mukohara T PI3K mutations in breast cancer: prognostic and therapeutic implications
description	Toru MukoharaCancer Center and Division of Medical Oncology/Hematology, Kobe University Hospital, Kobe, JapanAbstract: The PI3K pathway is the most frequently enhanced oncogenic pathway in breast cancer. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (~30%) observed, along with protein loss of PTEN. Since the first discovery of PIK3CA mutations in solid malignancies in 2004, numerous studies have revealed the prognostic and therapeutic implications of these mutations. Although many issues remain unconfirmed, some have been carved in stone by the level of consistency they have shown among studies: 1) PIK3CA mutations are most likely to be observed in ER-positive/HER2-negative tumors, and are associated with other good prognostic characters; 2) PIK3CA mutations can coexist with other PI3K-enhancing mechanisms, such as HER2 amplification and PTEN protein loss; 3) PIK3CA mutations are potentially a good prognostic marker; 4) PIK3CA may predict a poorer tumor response to trastuzumab-based therapies, but its impact on disease-free survival and overall survival is uncertain; and 5) based on reports of early clinical trials, PIK3CA mutations do not guarantee a dramatic response to PI3K inhibitors. Collectively, there is currently no sufficient evidence to recommend routine genotyping of PIK3CA in clinical practice. Given that PIK3CA-mutant breast cancer appears to have a distinct tumor biology, development of more individualized targeted therapies based on the PIK3CA genotype is awaited.Keywords: PI3K, PIK3CA, prognostic factor, predictive factor, trastuzumab
format	article
author	Mukohara T
author_facet	Mukohara T
author_sort	Mukohara T
title	PI3K mutations in breast cancer: prognostic and therapeutic implications
title_short	PI3K mutations in breast cancer: prognostic and therapeutic implications
title_full	PI3K mutations in breast cancer: prognostic and therapeutic implications
title_fullStr	PI3K mutations in breast cancer: prognostic and therapeutic implications
title_full_unstemmed	PI3K mutations in breast cancer: prognostic and therapeutic implications
title_sort	pi3k mutations in breast cancer: prognostic and therapeutic implications
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/3fd2933d14fe461bb213d49ef70aed6c
work_keys_str_mv	AT mukoharat pi3kmutationsinbreastcancerprognosticandtherapeuticimplications
_version_	1718403133716037632

PI3K mutations in breast cancer: prognostic and therapeutic implications

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