Topoisomerase II α Gene alteration in Triple Negative Breast Cancer and Its Predictive Role for Anthracycline-Based Chemotherapy (Egyptian NCI Patients)

Document Type: Research Articles

Authors

1 Department of Pathology, National Cancer Institute, Cairo University, Egypt.

2 Department of Pathology, National Cancer Institute, Cairo University, and Children’s Cancer Hospital Egypt, Cairo, Egypt.

3 Department of Medical Oncology, National Cancer Institute, Cairo University, Egypt.

4 Department of Biostatistics and Cancer Epidemiology, National Cancer Institute, Cairo University, Egypt.

Abstract

Objective: Triple negative breast cancer is an aggressive variant of breast cancer; it forms about 15% of breast
cancer cases. It lacks the responsiveness to hormonal and targeted therapies. Anthracyclines remain the treatment option
for these patients. Anthracyclines are cardiotoxic, so predicting sensitivity of response by biological predictors may
have a role in selecting suitable candidates for these drugs. Material and methods: This study included 50 TNBC
cases, from National Cancer Institute, Cairo University(NCI-CU), Egypt, who underwent surgery and received adjuvant
chemotherapy. Archived blocks were obtained and immunostaining for Ki-67 LI and Fluorescent In situ Hybridization
(FISH) technique to assess TOP2A gene copy number and chromosome 17CEP status were done. Analysis of association
between TOP2A alterations and CEP17 polysomy as well as Ki-67 LI with other clinicopathological parameters was
done. Associations between the biological markers and event free survival (EFS) and overall survival (OS), were also
performed. Results: TOP2A alteration was seen in 9/50 cases (5 amplified and 4 deleted). CEP17 Polysomy was detected
in 14% of cases. Most of patients (80%) showed Ki-67 LI ≥20%. There was a significant association between TOP2A
gene and CEP17 status. Outcome was better with abnormal TOP2A gene status and CEP17 polysomy, radiotherapy
and combined anthracyclines and taxanes in the adjuvant setting, however P-values were not significant. Conclusion:
TOP2A gene alterations and CEP17 polysomy may have prognostic and predictive role in TNBC treated with adjuvant
Anthracyclines.

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