127. Abnormalities of erbB oncogenes in locally advanced breast cancer (LABC)

• Published in: Reports of practical oncology and radiotherapy Vol. 8; p. S235
• Main Authors: Wełnicka-Jaśkiewicz, M., Żaczek, A., Konopa, A., Świerblewski, M., Bielawski, K.
• Format: Journal Article
• Language: English
• Published: Elsevier Urban & Partner (Poland) 2003
• ISSN: 1507-1367; 2083-4640
• DOI: 10.1016/S1507-1367(03)70611-7

The erbB family of proto-oncogenes (erbB-1, erbB-2, erbB-3, erbB-4) and their receptors play an important role in normal cell growth and neoplastic transformation. Literature data indicate that some abnormalities of erbB oncogene play an important role in breast cancer development, correlate with tumor aggressiveness and with worse clinical outcome. Therefore, these abnormalities may potentially have prognostic and therapeutic relevance. Aim of the study: To determine the number of gene copies within erbB oncogene family in breast cancer. The relationship of abnormalities /CA/n in the dinucleotides and the loss of heterozygosity (LOH) in erbB-1 were analyzed in relation to clinical and pathological features of the tumors and to chemotherapy response.
Study subjects included 50 chemotherapy naive LABC (any T, N2, any N, T4) patients (pts). All pts received induction chemotherapy. Tumor measurement was performed after each cycle and at the completion of induction chemotherapy. Double differential PCR (ddPCR) was used for detection of erbB oncogene family abnormalities (gene amplification/deletion). Microsatellite polymorphism of erbB-1 was examined by PCR with fluorescently labeled primers, followed by capillary electrophoresis and quantitative analysis of PCR product with GeneScanTM system, using automated ABI PRSM 310.
Amplifications of erbB-1, erbB-2, erbB-3, erbB-4 (defined as AGCN value of > 1.6) were detected in 5.9%, 26.5%, 2.9% and 2.9% of examined cases, respectively. Deletions, defined as AGCN value of < 004, accompanied only erbB-1 amplification and occurred in 26.5% of all cases. There was a polymorphic simple sequence repeat region of 12–20 CA detected in the first intron of erbB-1. Homozygotes comprised 31% of the examined group. The majority of homozygous pts revealed 14/14 CA repeat combination. LOH (most frequently affecting shorter allele) was determined in breast cancer heterozygotes and occurred in 50% of cases. Correlations between these findings and clinical outcomes will be presented.