PR-4

The U.S. breast cancer incidence rate is highest overall among Caucasian-American (CA) women; however, early-onset breast cancer occurs at an increased frequency among African-American (AA) women. This national trend is particularly notable in Alabama, where the relative risk of breast cancer in young AA women is twice that observed in their CA counterparts. AA women also have historically poorer breast cancer outcomes, which may be a consequence of more aggressive disease. The underlying genetic factors contributing to these racial disparities in breast cancer are poorly understood. To better define the genetic contribution to racial/ethnic disparities in breast cancer, we are correlating tumor biology with genome copy number alterations of breast tumors from Alabama women. We hypothesized that the differences in tumor phenotype observed between AA and CA early-onset breast cancer patients correlates with specific patterns of genomic aberrations. Our initial study includes 25 AA and 47 CA patients diagnosed with breast cancer at or below the age of 50. Consistent with previous reports, young AA women were significantly more likely to present with high-grade tumors. CA women were significantly more likely to present with the less aggressive breast tumor subtypes, as defined by estrogen receptor, progesterone receptor and HER2-neu expression. AA tumors were also found to exhibit a less favorable expression pattern with respect to the prognostic markers, p27 and p53. DNA from age and grade matched tumors were analyzed for copy number variations by comparative genomic hybridization (CGH) using a high-resolution whole genome BAC array (32K BAC array). Array CGH analysis of thirteen samples to date has identified a subset of loci that are differentially altered based on ethnicity. In addition, copy number variations have been identified which discriminate breast tumors based on tumor subtype, HER2 status, and ER status. Identification of chromosomal aberration patterns associated with specific pathologic factors may enhance assessment of breast cancer prognosis. In addition, these studies may lead to the identification of loci that contribute to the increased incidence and aggressiveness of early onset breast cancer in AA women.

First AACR International Conference on the Science of Cancer Health Disparities-- Nov 27-30, 2007; Atlanta, GA