Background: Breast cancer in African American women (AAW) occurs at a younger age and has a significantly more aggressive phenotype, including negative ER, and positive lymph node and p53 status and frequently shares the same unique pathological characteristics as tumors from patients with inherited BRCA1 mutations. Genomic instability has been associated with poor prognosis in patients with breast cancer, thus levels and patterns of allelic imbalance (AI) were assessed in tumors from AAW and Caucasian women (CW) to determine whether genomic instability is associated with the BRCA1-like phenotype and poor outcome in AAW.
Methods: DNA was extracted from primary breast tumors from AAW (n=22) and CW (n=144) after laser microdissection to isolate pure tumor cell populations. Genomic instability was detected using 52 microsatellite markers representing 26 chromosomal regions frequently altered in breast cancer. Statistical analyses were performed using Fisher’s exact tests and Student t-tests.
Results: Tumors from AAW had significantly (P<0.05) more aggressive characteristics, including positive lymph node and negative PR status, higher stage at diagnosis, BRCA1-like phenotype and poor outcome. Overall levels of instability were higher in tumors from CW (24%) compared to AAW (19%), although this difference did not reach the level of significance. The highest frequency of AI in tumors from AAW was at chromosome 17p13.1 (41%), while in CW, 17p13.3 was the most frequently altered region (40%). Levels of AI did not differ significantly between AAW and CW at any of the 26 chromosomal regions assayed.
Conclusions: Although tumors from AAW had more aggressive characteristics, lack of association between genomic instability and tumor phenotype suggest that differences in behavior and outcome are not driven by the accumulation of chromosomal alterations within the tumor. These results suggest that clinical differences between AAW and CW are not innate to the tumor itself but may instead be attributable to differences in host susceptibility, gene-environment response and/or tumor microenvironment.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA