TY - JOUR
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.
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41598-018-23733-4
DO - 10.1038/s41598-018-23733-4
M3 - Article
C2 - 29700408
AN - SCOPUS:85045981399
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 6574
ER -