Role of CCND1 and C-MYC oncogenes in metastatic breast cancer patients treated by herceptin

Introduction

In breast cancer (BC), several cytogenetic markers are routinely investigated (Her2, progesterone and estrogen receptors) that distribute patients into different diagnostic groups, determine prognosis and predict effectiveness of therapy. Additional genetic markers can improve prediction or prognosis in BC patients. C-MYC and CCND1 gene aberrations frequently found in BC were chosen for this study.

Methods

The status of C-MYC, CCND1 genes, chromosomes 8 and 11 were determined on 74 patients from a group of 103 BC patients treated with herceptin in a palliative regime, using FISH assay on formalin-fixed paraffin-embedded tissue samples. One hundred nuclei per sample were analyzed in each sample. Clinical data were correlated with our cytogenetic results.

Results

Amplifications of CCND1 and C-MYC were occurring together in most cases (P < 0.0001), especially in Her-2/neu-negative cases (P = 0.01, resp. 0.03). Progesterone receptor positivity was associated with CCND1, resp. C-MYC increased copy number (P = 0.039, resp. 0.038). Amplification (ratio gene/chromosome ≥2.2) of CCND1, resp. C-MYC was determined in 8.1% (6/74), resp. 12.2% (9/74) cases. Polysomy (copy number ≥3.0) of chromosome 11, resp. 8 was determined in 6.8% (5/74), resp. 16.2% (12/74) cases.

Conclusion

Increased copy numbers of CCND1 and C-MYC were associated with progesterone receptor positivity and Her-2/neu negativity. Clinical relevance of our findings will be presented.