E-cadherin breast tumor expression, risk factors and survival: Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium.
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Date
2018-04-26Author
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, K-U
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
Type
Journal Article
Metadata
Show full item recordAbstract
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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Subject
Humans
Breast Neoplasms
Receptor, erbB-2
Cadherins
Receptors, Estrogen
Receptors, Progesterone
Prognosis
Proportional Hazards Models
Odds Ratio
Risk Factors
Case-Control Studies
Gene Expression
Adult
Aged
Middle Aged
Female
Biomarkers, Tumor
Research team
Complex Trait Genetics
Aetiological Epidemiology
Language
eng
Date accepted
2018-03-16
License start date
2018-04-26
Citation
Scientific reports, 2018, 8 (1), pp. 6574 - ?
Publisher
NATURE PORTFOLIO