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Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer.
Arnes, Jarle B; Brunet, Jean-Sébastien; Stefansson, Ingunn; Bégin, Louis R; Wong, Nora; Chappuis, Pierre O; Akslen, Lars A; Foulkes, William D.
Afiliación
  • Arnes JB; Department of Pathology, The Gade Institute, Haukeland University Hospital, Bergen, Norway.
Clin Cancer Res ; 11(11): 4003-11, 2005 Jun 01.
Article en En | MEDLINE | ID: mdl-15930334
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.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Cadherinas / Proteína BRCA1 Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Aged / Female / Humans / Middle aged Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2005 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Cadherinas / Proteína BRCA1 Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Aged / Female / Humans / Middle aged Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2005 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Estados Unidos