Abstract
Background: Triple negative (TN) tumors are characterized by aggressive behavior and, the negative hormone receptor and HER2 status precludes the use of personalized therapies such as tamoxifen and trastuzumab. African American women have higher rates of both breast cancer mortality as well as TN breast tumors. What remains unknown is how much of these disparities can be attributed to molecular differences between populations.
Methods: The Clinical Breast Care Project database was queried to identify African American women with triple negative, high-grade tumors. Caucasian women with highgrade TN tumors were then matched by age at diagnosis, tumor stage, size and lymph node status. RNA was isolated after laser microdissection of the tumor and hybridized to HG U133A 2.0 microarrays. Data was analyzed using Partek Genomics Suite.
Results: Principal Component Analysis accurately clustered the triple negative specimens by ethnicity. Using a false-discovery rate (FDR) p-value <0.05 with a minimum 2.0-fold change of expression, 132 probes from 117 genes were differentially expressed. Hierarchical clustering using a subset of these probes (P<0.00001) representing 23 known genes reliably partitioned all samples as African American or Caucasian. Genes differentially expressed include lower expression of AQP5, VEGF and RAD51C and higher expression of hemoglobin B, and complement factors CFD and C4A in tumors from African Americans.
Discussion: Despite matching of tumors by clinicopathological characteristics, molecular profiles of triple negative breast tumors differed between AAW and CW. These differences may serve as molecular targets for the development of novel prevention strategies and therapeutics to reduce the risk of developing and improve treatment of African American women with triple negative breast cancer.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B31.
RSS Feeds