Placental Cadherin and the Basal Epithelial Phenotype of BRCA1-Related Breast Cancer

• Published in: Clinical cancer research Vol. 11; no. 11; pp. 4003 - 4011
• Main Authors: ARNES, Jarle B, BRUNET, Jean-Sébastien, STEFANSSON, Ingunn, BEGIN, Louis R, WONG, Nora, CHAPPUIS, Pierre O, AKSLEN, Lars A, FOULKES, William D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.06.2005
• Subjects: Aged; Antineoplastic agents; Biological and medical sciences; BRCA1 Protein - genetics; BRCA2 Protein - genetics; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cadherins - analysis; Cell Cycle Proteins - analysis; Cyclin E - analysis; Cyclin-Dependent Kinase Inhibitor p27; Female; Hereditary breast cancer; Humans; Immunohistochemistry; Keratin-5; Keratins - analysis; Medical sciences; Middle Aged; Multivariate Analysis; Mutation; Pharmacology. Drug treatments; Phenotype; Prognosis; Receptor, ErbB-2 - analysis; Receptors, Estrogen - analysis; stem cells; survival; Survival Analysis; Tumor Suppressor Protein p53 - analysis; Tumor Suppressor Proteins - analysis; Mammary gland diseases; Phenotype; Placenta; Fetal membrane; Breast cancer; Malignant tumor; Cadherin; BRCA1 gene; Tumor suppressor gene
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-2064

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.