Gene amplification is an important mechanism for oncogene activation, a crucial step in
carcinogenesis. Compared to female
breast cancer, little is known on the genetic makeup of
male breast cancer, because large series are lacking. Copy number changes of 21
breast cancer related genes were studied in 110 male breast
cancers using multiplex
ligation-dependent probe amplification. A ratio of >1.3 was regarded indicative for gene copy number gain and a ratio >2.0 for gene amplification. Data were correlated with clinicopathological features, prognosis and 17 genes were compared with a group of female breast
cancers. Gene copy number gain of CCND1,
TRAF4, CDC6 and MTDH was seen in >40 % of the
male breast cancer cases, with also frequent amplification. The number of genes with copy number gain and several single genes were associated with high grade, but only CCND1 amplification was an independent predictor of adverse survival in Cox regression (p = 0.015; hazard ratio 3.0). In unsupervised hierarchical clustering a distinctive group of
male breast cancer with poor prognosis (p = 0.009; hazard ratio 3.4) was identified, characterized by frequent CCND1, MTDH, CDC6, ADAM9,
TRAF4 and MYC copy number gain. Compared to female breast
cancers, EGFR (p = 0.005) and CCND1 (p = 0.041) copy number gain was more often seen in
male breast cancer, while copy number gain of EMSY (p = 0.004) and CPD (p = 0.001) and amplification in general was less frequent. In conclusion, several female
breast cancer genes also seem to be important in male breast
carcinogenesis. However, there are also clear differences in copy number changes between male and female breast
cancers, pointing toward differences in
carcinogenesis between male and female
breast cancer and emphasizing the importance of identifying
biomarkers and therapeutic agents based on research in
male breast cancer. In addition CCND1 amplification seems to be an independent prognosticator in
male breast cancer.