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

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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.

Original languageEnglish
Article number6574
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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    Horne, H. N., Oh, H., Sherman, M. E., Palakal, M., Hewitt, S. M., Schmidt, M. K., Milne, R. L., Hardisson, D., Benitez, J., Blomqvist, C., Bolla, M. K., Brenner, H., Chang-Claude, J., Cora, R., Couch, F. J., Cuk, K., Devilee, P., Easton, D. F., Eccles, D. M., ... Figueroa, J. 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), [6574]. https://doi.org/10.1038/s41598-018-23733-4