Predictive value of topoisomerase II alpha protein for clinicopathological characteristics and prognosis in early breast cancer.

e12586 Background: Topoisomerase II alpha (TOP2A) has been identified as a proliferation marker, of which the most common method for detection is immunohistochemistry (IHC). However, the optimal cut-off of TOP2A expression regarding prognostic value remains controversial. This study was to identify the optimal cut-off value of TOP2A expression and its correlation with clinicopathological variables and prognosis in early-stage breast cancer in China. Methods: Between January 2013 and January 2015, a total of 1084 early breast cancer patients were enrolled. The optimal cut-off of TOP2A expression was assessed using the minimum P value approach. Correlations between TOP2A expression and clinicopathological characteristics were explored by the Spearman’s correlation analysis, while the impact of TOP2A expression on disease free survival (DFS) and overall survival (OS) was evaluated by the Kaplan-Meier methods. Univariate and multivariate Cox regression analyses were executed to identify statistically significant prognostic factors. Results: The optimal cut-off value of TOP2A was recommended as 15%. Overall, 603 (55.6%) patients were TOP2A over-expression and 481 (44.4%) patients were TOP2A low-expression. TOP2A over-expression was in positive associations with a higher ki67 index (r = 0.83, P < 0.001), HER2 positive (r = 0.24, P < 0.001), a larger tumor size (r = 0.15, P < 0.001), and a higher histologic grade (r = 0.59, P < 0.001), and in a significantly negative correlation with hormone receptor (HR) positive expression in early breast cancer (r = -0.40, P < 0.001). TOP2A over-expression significantly associated with worse DFS (P = 0.001) and OS (P < 0.001) and was an independent prognostic factor for both DFS (hazard ratio [HR] = 1.71; 95% confidence interval [95%CI]: 1.13-2.59, P = 0.02) and OS (HR = 3.53; 95%CI: 1.53-8.23, P = 0.003) in stage I-II breast cancer patients. Conclusions: To our knowledge, this is the first study to recommend the optimal cut-off value of TOP2A expression in breast cancer. The TOP2A expression is significantly correlated with HER2 status, ki67 index, tumor size, histologic grade, and HR status, and could be a surrogate indicator for poor prognosis of early breast cancer.

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Correlation between expression of topoisomerase II alpha with Ki-67 and tumor size in luminal B-Like Indonesian breast cancer patients

Annals of Oncology ◽

10.1093/annonc/mdy426.019 ◽

2018 ◽

Vol 29 ◽

pp. ix6

Author(s):

H. Putri ◽

M.A. Kristina ◽

D. Widjaja ◽

B.A. Baskoro ◽

E. Kristiani

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Size ◽

Topoisomerase Ii ◽

Breast Cancer Patients ◽

Topoisomerase Ii Alpha ◽

Ki 67 ◽

Luminal B

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Topoisomerase II alpha as a marker predicting anthracyclines’ activity in early breast cancer patients: Ready for the primetime?

European Journal of Cancer ◽

10.1016/j.ejca.2008.09.014 ◽

2008 ◽

Vol 44 (18) ◽

pp. 2791-2798 ◽

Cited By ~ 32

Author(s):

Angelo Di Leo ◽

Laura Biganzoli ◽

Wederson Claudino ◽

Sara Licitra ◽

Marta Pestrin ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Early Breast Cancer ◽

Topoisomerase Ii ◽

Breast Cancer Patients ◽

Topoisomerase Ii Alpha

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Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response

The Breast ◽

10.1016/j.breast.2006.06.008 ◽

2007 ◽

Vol 16 (1) ◽

pp. 86-93 ◽

Cited By ~ 47

Author(s):

A. Rody ◽

T. Karn ◽

R. Gätje ◽

A. Ahr ◽

C. Solbach ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Patients ◽

Expression Profiling ◽

Topoisomerase Ii ◽

Tumor Response ◽

Breast Cancer Patients ◽

Topoisomerase Ii Alpha ◽

Protein Tau ◽

Her 2

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A meta-analysis of phase III trials evaluating the predictive value of HER2 and topoisomerase II alpha in early breast cancer patients treated with CMF or anthracycline-based adjuvant therapy.

10.1158/0008-5472.sabcs-705 ◽

2009 ◽

Cited By ~ 14

Author(s):

A Di Leo ◽

J Isola ◽

F Piette ◽

B Ejlertsen ◽

KI Pritchard ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Therapy ◽

Cancer Patients ◽

Predictive Value ◽

Topoisomerase Ii ◽

Meta Analysis ◽

Phase Iii ◽

Breast Cancer Patients ◽

Topoisomerase Ii Alpha ◽

Phase Iii Trials

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674 Topoisomerase II alpha (TOP2A) alterations as a predictive marker for epirubicin sensitivity in 805 high-risk breast cancer patients. A randomised DBCG trial (DBCG89D)

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(03)90705-1 ◽

2003 ◽

Vol 1 (5) ◽

pp. S202-S203 ◽

Cited By ~ 4

Author(s):

A. Knoop ◽

H. Knudsen ◽

E. Balslev ◽

B. Rasmussen ◽

J. Overgaard ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Cancer Patients ◽

Topoisomerase Ii ◽

Predictive Marker ◽

Breast Cancer Patients ◽

Topoisomerase Ii Alpha ◽

High Risk Breast Cancer ◽

High Risk Breast ◽

Risk Breast Cancer

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Comparative value of tumour grade, hormonal receptors, Ki-67, HER-2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy

European Journal of Cancer ◽

10.1016/s0959-8049(03)00675-0 ◽

2004 ◽

Vol 40 (2) ◽

pp. 205-211 ◽

Cited By ~ 179

Author(s):

T. Petit ◽

M. Wilt ◽

M. Velten ◽

R. Millon ◽

J.-F. Rodier ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Topoisomerase Ii ◽

Predictive Markers ◽

Breast Cancer Patients ◽

Tumour Grade ◽

Topoisomerase Ii Alpha ◽

Ki 67 ◽

Hormonal Receptors ◽

Her 2

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Prognostic significance of HER-2/neu over-expression on the incidence of brain metastasis in newly diagnosed breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.649 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 649-649 ◽

Cited By ~ 1

Author(s):

B. S. Abdulkarim ◽

Z. Gabos ◽

R. Sinha ◽

J. Hanson ◽

N. Chauhan ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Size ◽

Univariate Analysis ◽

Prognostic Significance ◽

Newly Diagnosed ◽

Breast Cancer Patients ◽

Over Expression ◽

Increased Risk ◽

Her 2

649 Background: As systemic therapy improves, brain metastases (BM) from breast cancer are becoming increasingly evident. An increased risk of BM in HER-2/neu over-expressing metastatic breast cancer patients has been suggested. However, the relationship between HER-2/neu over-expression and the risk of BM in newly diagnosed breast cancer patients is unknown. Methods: To determine incidence of BM in HER-2/neu over-expressing breast cancer patients, a cohort of patients between 01/1998 and 12/2003 with uniform HER-2/neu testing were identified from a cancer registry. A total of 460 patients with HER-2/neu over-expression and 500 patients with HER-2/neu negative disease were reviewed. Patients were excluded if there was breast cancer diagnosed before 01/1998 or others cancer. A total of 301 HER-2/neu over-expressing and 363 HER-2/neu negative patients were included for this analysis. The association between histological features and the occurrence of BM were evaluated with univariate and multivariate analyses. Results: BM were identified in 8% (24 patients) of HER-2/neu over-expressing breast cancer patients compared to only 1.7% (6 patients) in the HER-2/neu negative patients (hazard ratio 5.15 [2.079–12.78], p=0.0001). In patients with recurrent disease, the proportion of BM for HER-2/neu over-expressing patients was 24% compared to 10% in HER-2/neu negative patients. HER-2/neu over-expression, tumor size >2cm, ≥ 4 nodes positive and grade 2/3 were predictors of BM in univariate analysis. In multivariate analysis, HER-2/neu over-expression and tumor size>2cm were an independent prognostic factors for the development of BM, while hormone receptors expressions was protective (p=0.02). Conclusions: Our population based study show that newly diagnosed HER-2/neu over-expressing breast cancer patients are at significantly increased risk for BM. As most BM occur in HER-2/neu over-expressing patients with systemic metastatic disease, these findings could prompt consideration of brain prophylaxis strategies and/or serial radiologic screening to detect asymptomatic BM. No significant financial relationships to disclose.

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Risk factors of brain metastasis in a series of Egyptian breast cancer patients: A single-institution experience.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.50 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 50-50

Author(s):

H. A. Azim ◽

R. A. Malek ◽

D. Abdelmonem ◽

S. Amin ◽

M. Abdelsalam

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Brain Metastasis ◽

Cancer Patients ◽

Tumor Size ◽

Lymph Node Involvement ◽

Breast Cancer Patients ◽

Over Expression ◽

Node Involvement

50 Background: Incidence of cerebral metastasis is increasing among breast cancer patients. Many factors have been reported associated with increased risk of brain metastasis. The aim of this retrospective analysis is to investigate the predictive factors for the development of brain metastasis in breast cancer patients. Methods: We retrospectively analyzed histologically proven breast cancer patients who presented to Cairo Oncology Center (COC) in the period from 1999 till 2008, with follow up period of 6 months at least for those in adjuvant setting. The following factors were analyzed: age, tumor size and grade, nodal status, ER, PgR and HER2 over-expression status. Results: Our study included 2,338 patients. 96 patients (4.1%) experienced brain metastasis during the course of their disease. 3 patients had brain metastasis among other sites of distant spread at first presentation to COC. 30 out of 96 patients (31.25%) with localized breast cancer had brain metastasis at first relapse with 13 (13.5%) of them had isolated brain metastasis. In a median follow-up of 37.1 months (6-277) the median time to develop brain metastasis was 26.5 months (0-144). Based on univariate analysis, the following variables were associated with shorter time to develop brain metastasis: tumor size more than 5 cm (HR = 2.1, 95% CI 1.14-3.87), lymph node involvement at diagnosis (HR = 1.57, 95%CI 1.17-2.10), ER negativity (HR = 1.58, 95%CI 1.33-1.73), PgR negativity (HR = 1.55, 95%CI 1.29-1.72) and HER2-neu over-expression (HR = 2.68, 95%CI 1.51-4.75). On multivariate analysis, only patients with lymph node involvement at diagnosis and those with HER2-neu positive breast cancer were associated with shorter time to develop brain metastasis. Conclusions: We concluded that HER2 over-expression as well as lymph node involvement are the 2 main factors associated with shorter time to develop brain metastasis. These patients could be good candidates for trials investigating the role of any prophylactic intervention to decrease their risk to develop brain metastases.

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