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E-cadherin breast tumor expression, risk factors and survival: Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium

E-cadherin breast tumor expression, risk factors and survival: Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium
E-cadherin breast tumor expression, risk factors and survival: Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium
E-cadherin (CDH1) is a putative tumor suppressor gene implicated in breast carcinogenesis. Yet, whether risk factors or survival differ by E-cadherin tumor expression is unclear. We evaluated E-cadherin tumor immunohistochemistry expression using tissue microarrays of 5,933 female invasive breast cancers from 12 studies from the Breast Cancer Consortium. H-scores were calculated and case-case odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression. Survival analyses were performed using Cox regression models. All analyses were stratified by estrogen receptor (ER) status and histologic subtype. E-cadherin low cases (N = 1191, 20%) were more frequently of lobular histology, low grade, >2 cm, and HER2-negative. Loss of E-cadherin expression (score < 100) was associated with menopausal hormone use among ER-positive tumors (ever compared to never users, OR = 1.24, 95% CI = 0.97-1.59), which was stronger when we evaluated complete loss of E-cadherin (i.e. H-score = 0), OR = 1.57, 95% CI = 1.06-2.33. Breast cancer specific mortality was unrelated to E-cadherin expression in multivariable models. E-cadherin low expression is associated with lobular histology, tumor characteristics and menopausal hormone use, with no evidence of an association with breast cancer specific survival. These data support loss of E-cadherin expression as an important marker of tumor subtypes.
2045-2322
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Oh, Hannah
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Sherman, Mark E.
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Palakal, Maya
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Schmidt, Marjanka K.
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Milne, Roger L.
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Hardisson, David
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Benitez, Javier
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Bolla, Manjeet K.
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Brenner, Hermann
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Devilee, Peter
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Easton, Douglas F.
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Eccles, Diana M.
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Eilber, Ursula
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Hartikainen, Jaana M.
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Heikkilä, Päivi
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Holleczek, Bernd
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Hooning, Maartje J.
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Jones, Michael
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Keeman, Renske
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Mannermaa, Arto
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Muranen, Taru A.
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Nevanlinna, Heli
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Perez, Jose I.A.
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Pharoah, Paul D.P.
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Smit, Vincent T.H.B.M.
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Tengström, Maria
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van Asperen, Christi J.
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Van Deurzen, Carolien H.M.
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Van Leeuwen, Flora F.
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Van’t Veer, Laura J.
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García-closas, Montserrat
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Figueroa, Jonine D.
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Horne, Hisani N., Oh, Hannah, Sherman, Mark E., Palakal, Maya, Hewitt, Stephen M., Schmidt, Marjanka K., Milne, Roger L., Hardisson, David, Benitez, Javier, Blomqvist, Carl, Bolla, Manjeet K., Brenner, Hermann, Chang-claude, Jenny, Cora, Renata, Couch, Fergus J., Cuk, Katarina, Devilee, Peter, Easton, Douglas F., Eccles, Diana M., Eilber, Ursula, Hartikainen, Jaana M., Heikkilä, Päivi, Holleczek, Bernd, Hooning, Maartje J., Jones, Michael, Keeman, Renske, Mannermaa, Arto, Martens, John W.M., Muranen, Taru A., Nevanlinna, Heli, Olson, Janet E., Orr, Nick, Perez, Jose I.A., Pharoah, Paul D.P., Ruddy, Kathryn J., Saum, Kai-uwe, Schoemaker, Minouk J., Seynaeve, Caroline, Sironen, Reijo, Smit, Vincent T.H.B.M., Swerdlow, Anthony J., Tengström, Maria, Thomas, Abigail S., Timmermans, A. Mieke, Tollenaar, Rob A.E.M., Troester, Melissa A., van Asperen, Christi J., Van Deurzen, Carolien H.M., Van Leeuwen, Flora F., Van’t Veer, Laura J., García-closas, Montserrat and Figueroa, Jonine D. (2018) E-cadherin breast tumor expression, risk factors and survival: Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium. Scientific Reports, 8 (1). (doi:10.1038/s41598-018-23733-4).

Record type: Article

Abstract

E-cadherin (CDH1) is a putative tumor suppressor gene implicated in breast carcinogenesis. Yet, whether risk factors or survival differ by E-cadherin tumor expression is unclear. We evaluated E-cadherin tumor immunohistochemistry expression using tissue microarrays of 5,933 female invasive breast cancers from 12 studies from the Breast Cancer Consortium. H-scores were calculated and case-case odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression. Survival analyses were performed using Cox regression models. All analyses were stratified by estrogen receptor (ER) status and histologic subtype. E-cadherin low cases (N = 1191, 20%) were more frequently of lobular histology, low grade, >2 cm, and HER2-negative. Loss of E-cadherin expression (score < 100) was associated with menopausal hormone use among ER-positive tumors (ever compared to never users, OR = 1.24, 95% CI = 0.97-1.59), which was stronger when we evaluated complete loss of E-cadherin (i.e. H-score = 0), OR = 1.57, 95% CI = 1.06-2.33. Breast cancer specific mortality was unrelated to E-cadherin expression in multivariable models. E-cadherin low expression is associated with lobular histology, tumor characteristics and menopausal hormone use, with no evidence of an association with breast cancer specific survival. These data support loss of E-cadherin expression as an important marker of tumor subtypes.

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Accepted/In Press date: 16 March 2018
e-pub ahead of print date: 28 April 2018
Published date: 1 December 2018

Identifiers

Local EPrints ID: 420479
URI: https://eprints.soton.ac.uk/id/eprint/420479
ISSN: 2045-2322
PURE UUID: 6d5d3c03-a506-4fcb-b35e-6ef73097ebb8

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Date deposited: 08 May 2018 16:30
Last modified: 14 Mar 2019 05:10

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Contributors

Author: Hisani N. Horne
Author: Hannah Oh
Author: Mark E. Sherman
Author: Maya Palakal
Author: Stephen M. Hewitt
Author: Marjanka K. Schmidt
Author: Roger L. Milne
Author: David Hardisson
Author: Javier Benitez
Author: Carl Blomqvist
Author: Manjeet K. Bolla
Author: Hermann Brenner
Author: Jenny Chang-claude
Author: Renata Cora
Author: Fergus J. Couch
Author: Katarina Cuk
Author: Peter Devilee
Author: Douglas F. Easton
Author: Diana M. Eccles
Author: Ursula Eilber
Author: Jaana M. Hartikainen
Author: Päivi Heikkilä
Author: Bernd Holleczek
Author: Maartje J. Hooning
Author: Michael Jones
Author: Renske Keeman
Author: Arto Mannermaa
Author: John W.M. Martens
Author: Taru A. Muranen
Author: Heli Nevanlinna
Author: Janet E. Olson
Author: Nick Orr
Author: Jose I.A. Perez
Author: Paul D.P. Pharoah
Author: Kathryn J. Ruddy
Author: Kai-uwe Saum
Author: Minouk J. Schoemaker
Author: Caroline Seynaeve
Author: Reijo Sironen
Author: Vincent T.H.B.M. Smit
Author: Anthony J. Swerdlow
Author: Maria Tengström
Author: Abigail S. Thomas
Author: A. Mieke Timmermans
Author: Rob A.E.M. Tollenaar
Author: Melissa A. Troester
Author: Christi J. van Asperen
Author: Carolien H.M. Van Deurzen
Author: Flora F. Van Leeuwen
Author: Laura J. Van’t Veer
Author: Montserrat García-closas
Author: Jonine D. Figueroa

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