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

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article number6574
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Cadherins
Survival Analysis
Breast Neoplasms
Odds Ratio
Confidence Intervals
Estrogen Receptors
Neoplasms
Histology
Hormones
Tumor Biomarkers
Tumor Suppressor Genes
Proportional Hazards Models
Carcinogenesis
Breast
Logistic Models
Immunohistochemistry
Mortality

ASJC Scopus subject areas

  • General

Cite this

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

In: Scientific Reports, Vol. 8, No. 1, 6574, 01.12.2018.

Research output: Contribution to journalArticle

Horne, HN, Oh, H, Sherman, ME, Palakal, M, Hewitt, SM, Schmidt, MK, Milne, RL, Hardisson, D, Benitez, J, Blomqvist, C, Bolla, MK, Brenner, H, Chang-Claude, J, Cora, R, Couch, FJ, Cuk, K, Devilee, P, Easton, DF, Eccles, DM, Eilber, U, Hartikainen, JM, Heikkilä, P, Holleczek, B, Hooning, MJ, Jones, M, Keeman, R, Mannermaa, A, Martens, JWM, Muranen, TA, Nevanlinna, H, Olson, JE, Orr, N, Perez, JIA, Pharoah, PDP, Ruddy, KJ, Saum, KU, Schoemaker, MJ, Seynaeve, C, Sironen, R, Smit, VTHBM, Swerdlow, AJ, Tengström, M, Thomas, AS, Timmermans, AM, Tollenaar, RAEM, Troester, MA, Van Asperen, CJ, Van Deurzen, CHM, Van Leeuwen, FF, Van'T Veer, LJ, García-Closas, M & Figueroa, JD 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, vol. 8, no. 1, 6574. https://doi.org/10.1038/s41598-018-23733-4
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 ; Figueroa, Jonine D. / E-cadherin breast tumor expression, risk factors and survival : Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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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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T1 - E-cadherin breast tumor expression, risk factors and survival

T2 - Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium

AU - Horne, Hisani N.

AU - Oh, Hannah

AU - Sherman, Mark E.

AU - Palakal, Maya

AU - Hewitt, Stephen M.

AU - Schmidt, Marjanka K.

AU - Milne, Roger L.

AU - Hardisson, David

AU - Benitez, Javier

AU - Blomqvist, Carl

AU - Bolla, Manjeet K.

AU - Brenner, Hermann

AU - Chang-Claude, Jenny

AU - Cora, Renata

AU - Couch, Fergus J

AU - Cuk, Katarina

AU - Devilee, Peter

AU - Easton, Douglas F.

AU - Eccles, Diana M.

AU - Eilber, Ursula

AU - Hartikainen, Jaana M.

AU - Heikkilä, Päivi

AU - Holleczek, Bernd

AU - Hooning, Maartje J.

AU - Jones, Michael

AU - Keeman, Renske

AU - Mannermaa, Arto

AU - Martens, John W.M.

AU - Muranen, Taru A.

AU - Nevanlinna, Heli

AU - Olson, Janet E

AU - Orr, Nick

AU - Perez, Jose I.A.

AU - Pharoah, Paul D.P.

AU - Ruddy, Kathryn J

AU - Saum, Kai Uwe

AU - Schoemaker, Minouk J.

AU - Seynaeve, Caroline

AU - Sironen, Reijo

AU - Smit, Vincent T.H.B.M.

AU - Swerdlow, Anthony J.

AU - Tengström, Maria

AU - Thomas, Abigail S.

AU - Timmermans, A. Mieke

AU - Tollenaar, Rob A.E.M.

AU - Troester, Melissa A.

AU - Van Asperen, Christi J.

AU - Van Deurzen, Carolien H.M.

AU - Van Leeuwen, Flora F.

AU - Van'T Veer, Laura J.

AU - García-Closas, Montserrat

AU - Figueroa, Jonine D.

PY - 2018/12/1

Y1 - 2018/12/1

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