TOP2A gene copy number change in breast cancer

Abstract

Aims: The clinical significance of TOP2A as a prognostic marker has not been clarified. The aims of this study were to investigate the frequency of TOP2A copy number change; to correlate TOP2A with HER2 status, hormone receptor (HR) status and molecular subtype, and further to explore differences in breast cancer-specific survival according to TOP2A and HER2.

Methods: In this study, TOP2A, HER2 and chromosome 17 copy number were assessed in 670 cases of breast cancer using in situ hybridisation techniques. Gene to chromosome ratios ≥2 were classified as amplification. TOP2A deletion (gene to chromosome ratio ≤0.8) or monosomy (only one signal for both gene and chromosome in more than 75% of nuclei) were classified as gene loss.

Results: A strong association between TOP2A change and HR and HER2 status was found. During the first 5 years after diagnosis, the risk of death from breast cancer was significantly higher for cases with HER2 amplification irrespective of TOP2A status.

Conclusions: TOP2A copy number change was strongly associated with HR and HER2 status and as a prognostic marker TOP2A is probably of limited value.

Figure 1

Classification algorithm for molecular subtyping.

Figure 2

Kaplan–Meier plot. Breast cancer-specific survival (BCSS) according to TOP2A. p Value from log-rank test of differences in BCSS first 5 years after diagnosis was 0.02. After 5 years, the p value was 0.4.

Figure 3

Kaplan–Meier plot. Breast cancer-specific survival (BCSS) according to HER2. p Value from log-rank test of differences in BCSS first 5 years after diagnosis was <0.0001. After 5 years, the p value was 0.9.

Figure 4

Kaplan–Meier plot. Breast cancer-specific survival (BCSS) according to TOP2A and HER2. p Value from log-rank test of differences in BCSS first 5 years after diagnosis was <0.0001. After 5 years, the p value was 1.0.