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PKC and ER Are Associated with Triple-Negative Breast Cancers in African American and Caucasian Patients

DOI: 10.1155/2012/740353

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Abstract:

Although the incidence of breast cancer in the United States is higher in Caucasian women compared with African American women, African-American patients have more aggressive disease as characterized by a higher percentage of triple-negative breast cancers (TNBCs), high-grade tumors, and a higher mortality rate. PKCα is a biomarker associated with endocrine resistance and poor prognosis and ERβ is emerging as a protective biomarker. Immunohistochemical analysis of ERβ and PKCα expression was performed on 198 formalin-fixed paraffin-embedded primary infiltrating ductal carcinomas from 105 African-American and 93 Caucasian patients. PKCα is positively correlated with TNBC in patients of both races and with high tumor grade in African-American patients. Patients with TNBC express less nuclear ERβ compared with all other subtypes. We find no difference in frequency or intensity of PKCα or ERβ expression between African-American and Caucasian patients. PKCα and ERβ are discussed as potential therapeutic targets for the treatment of patients with TNBC. 1. Introduction Although African American women have a lower incidence of breast cancer than Caucasians, repeated studies have shown that they suffer from more aggressive disease characterized by diagnosis at an earlier age, later stage, higher grade, and greater mortality [1–4]. While socioeconomic factors contribute in part to this disparity in survival, they do not account for all differences noted between these two racial groups [3, 5, 6]. In particular, premenopausal African American women present with a higher incidence of triple-negative breast cancer (TNBC), a molecular subtype that has limited targeted therapeutic options [3, 7]. Current investigations are focused upon the identification of new therapeutic targets specific to the aggressive TNBC form of breast cancers found more frequently in young African American women and the development of more effective treatment modalities. One potential biomarker contributing to the aggressive nature of this disease in African American women is protein kinase Cα (PKCα). PKC is a serine/threonine protein kinase family of enzymes comprised of at least 12 isozymes that regulate numerous cellular functions [8]. PKCα in particular is involved in cell migration, apoptosis, differentiation, and proliferation and plays a critical role in several disease processes including cancer [9]. Overexpression of PKCα is a marker of poor prognosis of breast cancers and is associated with antiestrogen resistance, ERα-negative tumors, and tumor aggressiveness [10–13]. Therefore,

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