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Tumor topoisomerase II alpha status and response to anthracycline-based neoadjuvant chemotherapy in breast cancer.
Oncology. 2011; 80(3-4):269-77.O

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.

Authors+Show Affiliations

Department of Oncotherapy, University of Szeged, Szeged, Hungary.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21734419

Citation

Nikolényi, Alíz, et al. "Tumor Topoisomerase II Alpha Status and Response to Anthracycline-based Neoadjuvant Chemotherapy in Breast Cancer." Oncology, vol. 80, no. 3-4, 2011, pp. 269-77.
Nikolényi A, Sükösd F, Kaizer L, et al. Tumor topoisomerase II alpha status and response to anthracycline-based neoadjuvant chemotherapy in breast cancer. Oncology. 2011;80(3-4):269-77.
Nikolényi, A., Sükösd, F., Kaizer, L., Csörgo, 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), 269-77. https://doi.org/10.1159/000329038
Nikolényi A, et al. Tumor Topoisomerase II Alpha Status and Response to Anthracycline-based Neoadjuvant Chemotherapy in Breast Cancer. Oncology. 2011;80(3-4):269-77. PubMed PMID: 21734419.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor topoisomerase II alpha status and response to anthracycline-based neoadjuvant chemotherapy in breast cancer. AU - Nikolényi,Alíz, AU - Sükösd,Farkas, AU - Kaizer,László, AU - Csörgo,Erika, AU - Vörös,András, AU - Uhercsák,Gabriella, AU - Ormándi,Katalin, AU - Lázár,György, AU - Thurzó,László, AU - Brodowicz,Thomas, AU - Kahán,Zsuzsanna, Y1 - 2011/07/07/ PY - 2011/01/06/received PY - 2011/04/01/accepted PY - 2011/7/8/entrez PY - 2011/7/8/pubmed PY - 2011/9/29/medline SP - 269 EP - 77 JF - Oncology JO - Oncology VL - 80 IS - 3-4 N2 - 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. SN - 1423-0232 UR - https://www.unboundmedicine.com/medline/citation/21734419/Tumor_topoisomerase_II_alpha_status_and_response_to_anthracycline_based_neoadjuvant_chemotherapy_in_breast_cancer_ L2 - https://www.karger.com?DOI=10.1159/000329038 DB - PRIME DP - Unbound Medicine ER -