Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies.

<h4>Background</h4>Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate mortality for patients with the major subtypes of breast cancer as classified using five immu...

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Autores principales:	Fiona M Blows, Kristy E Driver, Marjanka K Schmidt, Annegien Broeks, Flora E van Leeuwen, Jelle Wesseling, Maggie C Cheang, Karen Gelmon, Torsten O Nielsen, Carl Blomqvist, Päivi Heikkilä, Tuomas Heikkinen, Heli Nevanlinna, Lars A Akslen, Louis R Bégin, William D Foulkes, Fergus J Couch, Xianshu Wang, Vicky Cafourek, Janet E Olson, Laura Baglietto, Graham G Giles, Gianluca Severi, Catriona A McLean, Melissa C Southey, Emad Rakha, Andrew R Green, Ian O Ellis, Mark E Sherman, Jolanta Lissowska, William F Anderson, Angela Cox, Simon S Cross, Malcolm W R Reed, Elena Provenzano, Sarah-Jane Dawson, Alison M Dunning, Manjeet Humphreys, Douglas F Easton, Montserrat García-Closas, Carlos Caldas, Paul D Pharoah, David Huntsman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/967dbe1e0a1d4068b8ebf3895d136d1c
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spelling	oai:doaj.org-article:967dbe1e0a1d4068b8ebf3895d136d1c2021-12-02T19:56:12ZSubtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies.1549-12771549-167610.1371/journal.pmed.1000279https://doaj.org/article/967dbe1e0a1d4068b8ebf3895d136d1c2010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20520800/pdf/?tool=EBIhttps://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate mortality for patients with the major subtypes of breast cancer as classified using five immunohistochemical markers, to investigate patterns of mortality over time, and to test for heterogeneity by subtype.<h4>Methods and findings</h4>We pooled data from more than 10,000 cases of invasive breast cancer from 12 studies that had collected information on hormone receptor status, human epidermal growth factor receptor-2 (HER2) status, and at least one basal marker (cytokeratin [CK]5/6 or epidermal growth factor receptor [EGFR]) together with survival time data. Tumours were classified as luminal and nonluminal tumours according to hormone receptor expression. These two groups were further subdivided according to expression of HER2, and finally, the luminal and nonluminal HER2-negative tumours were categorised according to expression of basal markers. Changes in mortality rates over time differed by subtype. In women with luminal HER2-negative subtypes, mortality rates were constant over time, whereas mortality rates associated with the luminal HER2-positive and nonluminal subtypes tended to peak within 5 y of diagnosis and then decline over time. In the first 5 y after diagnosis the nonluminal tumours were associated with a poorer prognosis, but over longer follow-up times the prognosis was poorer in the luminal subtypes, with the worst prognosis at 15 y being in the luminal HER2-positive tumours. Basal marker expression distinguished the HER2-negative luminal and nonluminal tumours into different subtypes. These patterns were independent of any systemic adjuvant therapy.<h4>Conclusions</h4>The six subtypes of breast cancer defined by expression of five markers show distinct behaviours with important differences in short term and long term prognosis. Application of these markers in the clinical setting could have the potential to improve the targeting of adjuvant chemotherapy to those most likely to benefit. The different patterns of mortality over time also suggest important biological differences between the subtypes that may result in differences in response to specific therapies, and that stratification of breast cancers by clinically relevant subtypes in clinical trials is urgently required.Fiona M BlowsKristy E DriverMarjanka K SchmidtAnnegien BroeksFlora E van LeeuwenJelle WesselingMaggie C CheangKaren GelmonTorsten O NielsenCarl BlomqvistPäivi HeikkiläTuomas HeikkinenHeli NevanlinnaLars A AkslenLouis R BéginWilliam D FoulkesFergus J CouchXianshu WangVicky CafourekJanet E OlsonLaura BagliettoGraham G GilesGianluca SeveriCatriona A McLeanMelissa C SoutheyEmad RakhaAndrew R GreenIan O EllisMark E ShermanJolanta LissowskaWilliam F AndersonAngela CoxSimon S CrossMalcolm W R ReedElena ProvenzanoSarah-Jane DawsonAlison M DunningManjeet HumphreysDouglas F EastonMontserrat García-ClosasCarlos CaldasPaul D PharoahDavid HuntsmanPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 7, Iss 5, p e1000279 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Fiona M Blows Kristy E Driver Marjanka K Schmidt Annegien Broeks Flora E van Leeuwen Jelle Wesseling Maggie C Cheang Karen Gelmon Torsten O Nielsen Carl Blomqvist Päivi Heikkilä Tuomas Heikkinen Heli Nevanlinna Lars A Akslen Louis R Bégin William D Foulkes Fergus J Couch Xianshu Wang Vicky Cafourek Janet E Olson Laura Baglietto Graham G Giles Gianluca Severi Catriona A McLean Melissa C Southey Emad Rakha Andrew R Green Ian O Ellis Mark E Sherman Jolanta Lissowska William F Anderson Angela Cox Simon S Cross Malcolm W R Reed Elena Provenzano Sarah-Jane Dawson Alison M Dunning Manjeet Humphreys Douglas F Easton Montserrat García-Closas Carlos Caldas Paul D Pharoah David Huntsman Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies.
description	<h4>Background</h4>Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate mortality for patients with the major subtypes of breast cancer as classified using five immunohistochemical markers, to investigate patterns of mortality over time, and to test for heterogeneity by subtype.<h4>Methods and findings</h4>We pooled data from more than 10,000 cases of invasive breast cancer from 12 studies that had collected information on hormone receptor status, human epidermal growth factor receptor-2 (HER2) status, and at least one basal marker (cytokeratin [CK]5/6 or epidermal growth factor receptor [EGFR]) together with survival time data. Tumours were classified as luminal and nonluminal tumours according to hormone receptor expression. These two groups were further subdivided according to expression of HER2, and finally, the luminal and nonluminal HER2-negative tumours were categorised according to expression of basal markers. Changes in mortality rates over time differed by subtype. In women with luminal HER2-negative subtypes, mortality rates were constant over time, whereas mortality rates associated with the luminal HER2-positive and nonluminal subtypes tended to peak within 5 y of diagnosis and then decline over time. In the first 5 y after diagnosis the nonluminal tumours were associated with a poorer prognosis, but over longer follow-up times the prognosis was poorer in the luminal subtypes, with the worst prognosis at 15 y being in the luminal HER2-positive tumours. Basal marker expression distinguished the HER2-negative luminal and nonluminal tumours into different subtypes. These patterns were independent of any systemic adjuvant therapy.<h4>Conclusions</h4>The six subtypes of breast cancer defined by expression of five markers show distinct behaviours with important differences in short term and long term prognosis. Application of these markers in the clinical setting could have the potential to improve the targeting of adjuvant chemotherapy to those most likely to benefit. The different patterns of mortality over time also suggest important biological differences between the subtypes that may result in differences in response to specific therapies, and that stratification of breast cancers by clinically relevant subtypes in clinical trials is urgently required.
format	article
author	Fiona M Blows Kristy E Driver Marjanka K Schmidt Annegien Broeks Flora E van Leeuwen Jelle Wesseling Maggie C Cheang Karen Gelmon Torsten O Nielsen Carl Blomqvist Päivi Heikkilä Tuomas Heikkinen Heli Nevanlinna Lars A Akslen Louis R Bégin William D Foulkes Fergus J Couch Xianshu Wang Vicky Cafourek Janet E Olson Laura Baglietto Graham G Giles Gianluca Severi Catriona A McLean Melissa C Southey Emad Rakha Andrew R Green Ian O Ellis Mark E Sherman Jolanta Lissowska William F Anderson Angela Cox Simon S Cross Malcolm W R Reed Elena Provenzano Sarah-Jane Dawson Alison M Dunning Manjeet Humphreys Douglas F Easton Montserrat García-Closas Carlos Caldas Paul D Pharoah David Huntsman
author_facet	Fiona M Blows Kristy E Driver Marjanka K Schmidt Annegien Broeks Flora E van Leeuwen Jelle Wesseling Maggie C Cheang Karen Gelmon Torsten O Nielsen Carl Blomqvist Päivi Heikkilä Tuomas Heikkinen Heli Nevanlinna Lars A Akslen Louis R Bégin William D Foulkes Fergus J Couch Xianshu Wang Vicky Cafourek Janet E Olson Laura Baglietto Graham G Giles Gianluca Severi Catriona A McLean Melissa C Southey Emad Rakha Andrew R Green Ian O Ellis Mark E Sherman Jolanta Lissowska William F Anderson Angela Cox Simon S Cross Malcolm W R Reed Elena Provenzano Sarah-Jane Dawson Alison M Dunning Manjeet Humphreys Douglas F Easton Montserrat García-Closas Carlos Caldas Paul D Pharoah David Huntsman
author_sort	Fiona M Blows
title	Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies.
title_short	Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies.
title_full	Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies.
title_fullStr	Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies.
title_full_unstemmed	Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies.
title_sort	subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/967dbe1e0a1d4068b8ebf3895d136d1c
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Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies.

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