Abstract #3084

BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive manifestation of primary breast cancer and its clinical presentation and the peculiar geographic distribution have suggested a possible viral etiology. Mouse Mammary Tumor, Human Herpes Virus 8 or Epstein-Barr virus (EBV) may play significant roles in the pathogenesis of the disease and account for the peculiar lymphangiogenic mechanism of growth and disease progression. In particular, EBV late membrane protein (LMP)-1 plays a critical role in tumor invasion lymphangiogenesis. In this study, EBV DNA was measured in each FNA sample from patients with IBC and locally advanced breast cancer (LABC) using real time PCR directed against 5 different targets within the EBV genome.
 PATIENTS AND METHODS: Sixty-eight fine needle aspirates (FNA) of breast cancer from patients with newly diagnosed IBC (n=18) and LABC (n=50) were examined. The FNA specimens were collected for the pharmacogenomic research program before any systemic therapy started. Median age of subjects was 53 yrs (range: 26-83 yrs). Total DNA was extracted from the FNA using the QIAmp Kit. EBV DNA were detected by quantitative polymerase chain reaction (QPCR) directed at five different targets within the EBV genome (BamH1W, LMP1, EBNA1, LMP2, and BZLF1) that encode products that are highly conserved across all EBV strains and important for viral pathogenesis. DNA extracted from Namalwa cells were used to construct the standard (R2 = 0.993); HL60 cells were used as EBV-negative controls. Data were collected and analyzed by Sequence Detection System software (Applied Biosystems Incorporated, ABI, Foster City, CA).
 RESULTS: EBV DNA was detected in freshly obtained breast cancer FNA samples using Q-PCR. The Q-PCR assays were sensitive to as low as 1 copy of EBV DNA per reaction. Of 68 breast tumor FNA specimens, EBV genes were detected in FNA from 4/18 (22%) IBC patients (range, 1-4 genes) and 5/50 (10%) LABC patients (range, 1-3 genes). Among the 9 positive specimens, BamH1W was detected in 6; EBNA1 in 5; LMP1 in 4; BZLF1 in 2; and LMP2 in 1, respectively.
 DISCUSSION AND CONCLUSIONS: Q-PCR is an effective method for detecting EBV DNA in FNA of breast cancer patients. The two most frequently detected EBV DNA sequences were BamH1W (6 of 9) and EBNA1 (5 of 9). BamH1W is a sequence that is frequently replicated throughout the EBV genome and EBNA1 is a reliable latent gene responsible for maintaining infection for life of the host. LMP-1 is a potential viral oncogene and was detected in 4/9 patients. The detection of these EBV sequences suggest latent EBV infections in IBC and LABC patients. The clinical significance of these findings warrants further investigation.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3084.

Thirty-first San Antonio Breast Cancer Symposium Dec 10-14, 2008; San Antonio, TX