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Background: Breast cancer incidence in the United States varies among ethnic groups. Overall incidence is highest among Caucasian women (CW); however, when stratified by age, the highest incidence of breast cancer occurs among African American women (AAW) under the age of 40. Mortality rates are also highest among AAW. The poor outcomes observed in AAW are frequently attributed to disparities in socioeconomic status, healthcare access, and cultural beliefs. However, tumor biology also differs among AAW and CW. Tumors from AAW share many characteristics with tumors from women with hereditary BRCA1 mutations including large size, aggressiveness, poor differentiation, high-grade nuclear atypia, frequent lymph node involvement, and estrogen receptor negativity. Therefore, biological and molecular factors may also contribute to the poor prognosis of AAW with breast cancer. In the present study, we have identified gene expression differences in normal breast tissue from disease-free AAW and CW that may predispose AAW to aggressive tumors and poor clinical prognoses.

Methods: Normal breast tissue (reductive mammoplasty and/or disease-free biopsy specimens) was obtained from AAW (n=26) and CW (n=22) enrolled in the Clinical Breast Care Project (CBCP). RNA was isolated using the Qiagen RNeasy Lipid Tissue Midi kit, amplified using the MessageAmp II aRNA Amplification kit (Ambion) and hybridized to the Affymetrix GeneChip Human Genome U133A 2.0 expression array. Differentially expressed genes were identified using Mann-Whitney testing (p ≤ 0.001).

Results: Eighty-nine genes were found to be differentially expressed in normal breast tissue from AAW and CW. Eighty-seven genes had lower expression in AAW compared to CW while two genes, PSPH and ACSM1, were more highly expressed in breast tissue from AAW. PSPH, encoding phoshoserine phosphatase, catalyzes the last step in L-serine biosynthesis. ACSM1, acyl-CoA synthetase medium chain family member 1, is involved in fatty acid oxidation.

Discussion: The CBCP provides us with a unique resource to study breast cancer in AAW. Because all women enrolled in the CBCP receive standardized treatment and care regardless of ethnicity, differences observed in gene expression are not confounded by differences in the quality of healthcare received. The increased expression of PSPH could potentially increase the amount of serine synthesized in the cell. As serine is used as an intermediate in the synthesis of other amino acids, phospholipids, and purines, this could have a profound impact on protein, lipid, and DNA metabolism. Likewise, increased expression of ACSM1 could increase the rate of fatty acid oxidation in the cell, resulting in a large increase in the amount of energy or ATP produced. Both conditions could promote cell growth and proliferation that would confer a growth advantage to breast cells in AAW that may increase their potential towards malignant transformation.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA