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
Pages (from-to)6574
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 26 Apr 2018
Externally publishedYes

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