Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer.

Abstract

PURPOSE:

BRCA1-related breast cancer frequently has a basal epithelial phenotype, and P-cadherin is a basal marker. We undertook a detailed evaluation of the relationship among P-cadherin, prognostic markers in breast cancer, and outcome.

EXPERIMENTAL DESIGN:

This study was restricted to 292 cases of first primary invasive breast cancer diagnosed in Ashkenazi Jewish women between 1980 and 1995. All available blocks were stained for P-cadherin, and 261 were included in the final statistical analyses, including 27 germ line BRCA1 mutation carriers and 8 BRCA2 mutation carriers. Descriptive analyses were done followed by survival analyses and a Poisson regression analysis.

RESULTS:

P-cadherin was present in 80 of the 261 breast cancers (31%) and was more frequently present in tumors that have a basal epithelial phenotype [i.e., high-grade, estrogen receptor- and KIP1 (p27(Kip1))-negative tumors, with expression of cytokeratin 5/6, cyclin E, TP53, and presence of BRCA1 mutations and vascular nests (all P < 0.001)]. In a univariate survival model, expression of P-cadherin was associated with a relative risk (RR) of death from breast cancer at a 10-year follow-up of 2.9 (95% confidence interval, 1.8-4.7; P < 0.0001) and was a predictor of poor univariate survival in both lymph node-negative and -positive breast cancers. In a multivariate analysis, the effect of P-cadherin levels was not independent of other basal-related markers. Multivariable interaction modeling showed that P-cadherin positivity was highly predictive of a poor prognosis in small, node-negative breast cancers (RR, 7.1; P = 0.006).

CONCLUSIONS:

P-cadherin is a marker for basal-like breast cancers and is strongly associated with the presence of a BRCA1 mutation. It is an adverse prognostic factor, particularly in small, node-negative breast cancers.

• Authors: Jarle B Arnes, Jean-Sébastien Brunet, Ingunn Stefansson, Louis R Bégin, Nora Wong, Pierre O Chappuis, Lars A Akslen, William D Foulkes
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 11 Pg. 4003-11 (Jun 01 2005) ISSN: 1078-0432 [Print] United States
• PMID: 15930334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BRCA1 Protein
• BRCA2 Protein
• Cadherins
• Cell Cycle Proteins
• Cyclin E
• KRT5 protein, human
• Keratin-5
• Receptors, Estrogen
• Tumor Suppressor Protein p53
• Tumor Suppressor Proteins
• Cyclin-Dependent Kinase Inhibitor p27
• Keratins
• Receptor, ErbB-2

Topics

• Aged
• BRCA1 Protein (genetics)
• BRCA2 Protein (genetics)
• Breast Neoplasms (genetics, metabolism, pathology)
• Cadherins (analysis)
• Cell Cycle Proteins (analysis)
• Cyclin E (analysis)
• Cyclin-Dependent Kinase Inhibitor p27
• Female
• Humans
• Immunohistochemistry
• Keratin-5
• Keratins (analysis)
• Middle Aged
• Multivariate Analysis
• Mutation
• Phenotype
• Prognosis
• Receptor, ErbB-2 (analysis)
• Receptors, Estrogen (analysis)
• Survival Analysis
• Tumor Suppressor Protein p53 (analysis)
• Tumor Suppressor Proteins (analysis)