Tumor topoisomerase II alpha status and response to anthracycline-based neoadjuvant chemotherapy in breast cancer

Alíz Nikolényi, Farkas Sükösd, László Kaizer, Erika Csörg, András Vörös, Gabriella Uhercsák, Katalin Ormándi, György Lázár, László Thurzó, Thomas Brodowicz, Zsuzsanna Kahán

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Abstract

Objectives: Individualized chemotherapy for breast cancer improves the outcome. Anthracyclines target the enzyme topoisomerase IIα (TOP2A). We set out to perform a retrospective study of the presence of gene abnormalities and the expression of TOP2A in a cohort of breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. Methods: Forty-three patients with 45 breast cancers were treated with neoadjuvant docetaxel-epirubicin with/without capecitabine chemotherapy. The TOP2A status of the cancers, determined retrospectively by fluorescent in situ hybridization and immunohistochemistry, was analyzed in relation to the standard clinical and pathological data. Results: Clinically and pathologically complete remission (pCR) was achieved in 15 (33.3%) and 9 (20%) cases, respectively. The TOP2A gene was amplified in 2 human epidermal growth factor receptor 2 (HER2)-positive cancers (8%), and 32 (84.2%) overall exhibited TOP2A expression in >15% of the cells. The expression of TOP2A exhibited a strong correlation with the expression of Ki67 (R = 0.743, p < 0.001), and was negatively correlated with estrogen receptors (ER; R = 0.404, p = 0.012) and progesterone receptors (R = 0.430, p = 0.007). The expression of TOP2A was not related to the amplification of the TOP2A gene or the HER2 status of the tumor. The proportions of Ki67-and TOP2A-positive tumor cells were significantly reduced after chemotherapy (56.1 ± 23.6 vs. 19.0 ± 27.7%, p = 0.004, and 41.0 ± 27.9 vs. 12.7 ± 24.8%, p < 0.001, respectively). The development of pCR was related to a high grade (p = 0.054), ER negativity (p = 0.027) and high TOP2A expression (p = 0.037). The expression of TOP2A was an independent predictor of pCR (OR = 1.460, for every 10% increase, 95% CI: 1.016-2.096, p = 0.041). After a median follow-up time of 31.0 months, neither relapse-free survival nor overall survival was related to the tumor response. Conclusions: TOP2A expression is a marker of the tumor's proliferation rate and sensitivity to anthracycline-based chemotherapy, and does not depend on the amplification of its gene.

Original languageEnglish
Pages (from-to)269-277
Number of pages9
JournalOncology
Volume80
Issue number3-4
DOIs
Publication statusPublished - Jul 1 2011

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Keywords

  • Anthracyclines
  • Breast cancer
  • Chemosensitivity
  • Primary neoadjuvant chemotherapy
  • Topoisomerase II alpha

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nikolényi, A., Sükösd, F., Kaizer, L., Csörg, E., Vörös, A., Uhercsák, G., Ormándi, K., Lázár, G., Thurzó, L., Brodowicz, T., & Kahán, Z. (2011). Tumor topoisomerase II alpha status and response to anthracycline-based neoadjuvant chemotherapy in breast cancer. Oncology, 80(3-4), 269-277. https://doi.org/10.1159/000329038