Comparison of genomic changes between tumors detected by screening mammography versus other methods

Abstract

10033 Background: The prognosis in patients with breast cancer detected by screening mammography has been found to be significantly better than those with similar-sized tumors detected by other methods (e.g. physical examination). (Joensuu, et al. 2004). Given the similar pathological characteristics, outcome differences may be explained by molecular differences within the tumors. To address this question, the relationship between genomic instability and methods of detection was assessed using allelic imbalance (AI) in similarly sized primary breast tumors from patients with breast cancer identified by screening mammography versus other methods. Methods: Patients with stage I breast cancer identified by screening mammography (n=50) versus other methods (n=50) were selected. Samples were matched between the two groups for clinical information. DNA was extracted from pure populations of tumor cells obtained by laser microdissection. Referent DNA was obtained from blood or disease-free skin samples from each patient. A panel of 52 microsatellite markers from 26 chromosomal regions commonly altered in breast cancer was used to assess AI, determined by the peak height ratio (≤0.35) between alleles from tumor and referent samples. Fisher’s exact test and Student’s t-tests were used to test for significant differences in levels of AI. Results: When clinical parameters such as age, ethnicity, menopause and status of tumor hormone receptors or HER2 were examined between tumor groups, no significant differences were detected. The overall frequency of AI between tumors detected by screening mammography (21.8%) versus other methods (22.3%) was similar (P=0.93). When patterns of AI were examined, none of the 26 chromosomal regions detected here showed a significant difference in AI events between the two groups. Conclusions: In this study, we have shown that global chromosomal differences are likely not the cause for the difference in tumor detection and prognosis between patients whose tumors were detected mammographically versus those whose were not. Prognostic factors known to correlate with disease aggressiveness and recurrence (e.g. hormone receptor or HER2 status) were also shown to not be associated with this difference in tumor detection among our patients. No significant financial relationships to disclose.