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Prognostic and predictive value of the combination of TOP2A and HER2 in node-negative tumors 2 cm or smaller (T1N0) breast cancer

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Abstract

Background

We aim to evaluate the prognostic and predictive value of TOP2A and HER2 expression in T1N0 breast cancer patients.

Methods

299 cases with T1N0 breast cancer were obtained from the Oncomine database (Cohort 1) and 963 of T1N0 breast cancer patients from Sun Yat-sen Memorial Hospital (Cohort 2) were retrospectively enrolled. Kaplan–Meier product was applied to estimate survival curve. Cox proportional hazard models was used to identify prognostic factors. We used PSM (propensity score matching) to balance clinicopathologic characteristics among four groups of different HER2/TOP2A status. Survival between groups and chemotherapy regimens were analyzed, before and after PSM.

Results

In Cohort 1, we found that the group with HER2+ and higher expression of TOP2A mRNA was associated with poor breast cancer-specific survival (BCSS) compared to the group of HER2− with lower expression of TOP2A mRNA. In Cohort 2, HER2+ patients with higher TOP2A protein expression had greater risk of recurrence and distant recurrence compared to HER2− patients with lower expression of TOP2A protein. Among the patients who developed both HER2+ and higher expression of TOP2A protein and received chemotherapy, patients who received an anthracycline-based regimen had a significantly better recurrence-free survival (RFS) than those with a non-anthracycline-based regime.

Conclusion

Patients with both HER2+ and high expression level of TOP2A protein predicts poor prognosis in T1N0 breast cancer patients. Patients with double positive for TOP2A protein and HER2 may benefit from anthracycline-based regimens.

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Abbreviations

BCSS:

Breast cancer-specific survival

CEF:

Cyclophosphamide plus epirubicin plus 5-FU

CMF:

Cyclophosphamide plus methotrexate plus 5-FU

CT:

Chemotherapy

DFS:

Disease-free survival

DRFS:

Distant recurrence-free survival

ER:

Estrogen receptors

ET:

Endocrine therapy

FISH:

Fluorescence in situ hybridization

HER2:

Human epidermal growth factor receptor 2

HR:

Hormone receptor status

IHC:

Immunohistochemistry

NCCN:

National comprehensive cancer network

OS:

Overall survival

PR:

Progesterone receptors

PS:

Propensity scores

PSM:

Propensity score matching

Ref.:

Reference

RFS:

Recurrence-free survival

RT:

Radiotherapy

TNBC:

Triple-negative breast cancer

TOP2A:

Topoisomerase IIα

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Acknowledgements

This work is supported by the National Key R&D Program of China (2017YFC1309103 and 2017YFC1309104); the Natural Science Foundation of China (81672594, 81772836 and 81872139); Clinical Innovation Project of Guangzhou regenerative medicine and health Guangdong laboratory (2018GZR0201004); Sun Yat-sen memorial hospital cultivation project for clinical research (SYS-C-201805).

Author information

Authors and Affiliations

  1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, People’s Republic of China

    Wenjing Zhong, Yaping Yang, Wanyi Lin, Gehao Liang, Yun Ling, Zihao Liu, Zhenluan Tian, Qun Lin, Qing Luo & Chang Gong

  2. Department of Breast Surgery, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, People’s Republic of China

    Wenjing Zhong, Yaping Yang, Wanyi Lin, Gehao Liang, Yun Ling, Zihao Liu, Zhenluan Tian, Qun Lin, Qing Luo & Chang Gong

  3. Department of Breast Surgery, Dongguan City People’s Hospital, Dongguan, People’s Republic of China

    Ailing Zhang

  4. Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China

    Jiajie Zhong, Juanjuan Yong & Yangyang Li

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  1. Wenjing Zhong
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  14. Chang Gong
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Correspondence to Chang Gong.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Wenjing Zhong, Yaping Yang and Ailing Zhang are co-first authors.

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Zhong, W., Yang, Y., Zhang, A. et al. Prognostic and predictive value of the combination of TOP2A and HER2 in node-negative tumors 2 cm or smaller (T1N0) breast cancer. Breast Cancer 27, 1147–1157 (2020). https://doi.org/10.1007/s12282-020-01142-8

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