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The role of topoisomerase IIα in predicting sensitivity to anthracyclines in breast cancer patients: a meta-analysis of published literatures

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Abstract

Topoisomerase IIα is not only a proliferation marker of tumor cells, but is also a target for anthracycline-based chemotherapy. Both in vitro and in vivo studies have shown that there is a relationship between topo IIα and chemosensitivity to anthracyclines, but the predictive role of topo IIα in breast cancer patients is still controversial. A meta-analysis based on published studies was performed to obtain an accurate assessment of the association between topo IIα and sensitivity to anthracycline-based chemotherapy. A total of 13 eligible studies, including 2,633 cases and 2,118 controls were identified. Topo IIα was associated with sensitivity to anthracyclines in locally advanced breast cancer patients who received neoadjuvant chemotherapy [five studies, including three using fluorescence in situ hybridization (FISH) and two using immunohistochemistry (IHC): relative risk (RR) = 1.93, 95% confidence interval (95% CI): 1.27–2.94, P = 0.002; two using FISH and three using IHC: RR = 1.98, 95% CI: 1.37–2.86, P < 0.001]. This association existed among three studies using FISH (RR = 2.03, 95% CI: 1.14–3.61, P = 0.017), but did not exist among three studies using IHC (P > 0.05). In early-stage breast cancer patients who received anthracycline-based adjuvant chemotherapy compared with non-taxane-based polychemotherapy, amplification [hazard ratio (HR) = 0.64, 95% CI: 0.49–0.83, P = 0.001; HR = 0.59, 95% CI: 0.35–1.01, P = 0.056] or deletion (HR = 0.82, 95% CI: 0.67–1.00, P = 0.051; HR = 0.58, 95% CI: 0.35–0.97, P = 0.036) of topo IIα was significantly associated with better recurrence-free survival and overall survival. In summary, the present meta-analysis suggests that topo IIα is a predictive factor for breast cancer patients who receive anthracycline-based chemotherapy. Larger and well-designed prospective studies are required to further evaluate the predictive role of topo IIα in clinical practice.

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References

  1. Berger JM, Gamblin SJ, Harrison SC, Wang JC (1996) Structure and mechanism of DNA topoisomerase II. Nature 379:225–232

    Article  PubMed  CAS  Google Scholar 

  2. Kellner U, Sehested M, Jensen PB, Gieseler F, Rudolph P (2002) Culprit and victim—DNA topoisomerase II. Lancet Oncol 3:235–243

    Article  PubMed  CAS  Google Scholar 

  3. Oakman C, Moretti E, Galardi F, Santarpia L, Di Leo A (2009) The role of topoisomerase IIalpha and HER-2 in predicting sensitivity to anthracyclines in breast cancer patients. Cancer Treat Rev 35:662–667

    Article  PubMed  CAS  Google Scholar 

  4. Durbecq V, Paesmans M, Cardoso F et al (2004) Topoisomerase-II alpha expression as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel. Mol Cancer Ther 3:1207–1214

    PubMed  CAS  Google Scholar 

  5. Di Leo A, Gancberg D, Larsimont D et al (2002) HER-2 amplification and topoisomerase IIalpha gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil. Clin Cancer Res 8:1107–1116

    PubMed  CAS  Google Scholar 

  6. Martin-Richard M, Munoz M, Albanell J et al (2004) Serial topoisomerase II expression in primary breast cancer and response to neoadjuvant anthracycline-based chemotherapy. Oncology 66:388–394

    Article  PubMed  CAS  Google Scholar 

  7. MacGrogan G, Rudolph P, Mascarel Id I et al (2003) DNA topoisomerase IIalpha expression and the response to primary chemotherapy in breast cancer. Br J Cancer 89:666–671

    Article  PubMed  CAS  Google Scholar 

  8. Coon JS, Marcus E, Gupta-Burt S, Seelig S, Jacobson K, Chen S, Renta V, Fronda G, Preisler HD (2002) Amplification and overexpression of topoisomerase IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer. Clin Cancer Res 8:1061–1067

    PubMed  CAS  Google Scholar 

  9. Park K, Kim J, Lim S, Han S (2003) Topoisomerase II-alpha (topoII) and HER2 amplification in breast cancers and response to preoperative doxorubicin chemotherapy. Eur J Cancer 39:631–634

    Article  PubMed  CAS  Google Scholar 

  10. Desmedt C, Azambuja E, Larsimont D et al (2009) Predicting the efficacy of anthracyclines in breast cancer (BC) patients: results of the neoadjuvant TOP trial. J Clin Oncol 27:523

    Google Scholar 

  11. Cardoso F, Durbecq V, Larsimont D et al (2004) Correlation between complete response to anthracycline-based chemotherapy and topoisomerase II-alpha gene amplification and protein overexpression in locally advanced/metastatic breast cancer. Int J Oncol 24:201–209

    PubMed  CAS  Google Scholar 

  12. Jarvinen TA, Holli K, Kuukasjarvi T, Isola JJ (1998) Predictive value of topoisomerase IIalpha and other prognostic factors for epirubicin chemotherapy in advanced breast cancer. Br J Cancer 77:2267–2273

    Article  PubMed  CAS  Google Scholar 

  13. Knoop AS, Knudsen H, Balslev E et al (2005) Retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. J Clin Oncol 23:7483–7490

    Article  PubMed  CAS  Google Scholar 

  14. Bartlett JM, Munro A, Cameron DA, Thomas J, Prescott R, Twelves CJ (2008) Type 1 receptor tyrosine kinase profiles identify patients with enhanced benefit from anthracyclines in the BR9601 adjuvant breast cancer chemotherapy trial. J Clin Oncol 26:5027–5035

    Article  PubMed  CAS  Google Scholar 

  15. O’Malley FP, Chia S, Tu D, Shepherd LE, Levine MN, Bramwell VH, Andrulis IL, Pritchard KI (2009) Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy. J Natl Cancer Inst 101:644–650

    Article  PubMed  Google Scholar 

  16. Slamon D, Eiermann W, Robert N et al (2009) Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC → T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC → TH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu positive early breast cancer patients: BCIRG 006 study. Cancer Res 69:500S

    Google Scholar 

  17. Di Leo A, Isola J, Piette F et al (2009) 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. Cancer Res 69:99S

    Google Scholar 

  18. Hayward JL, Carbone PP, Heuson JC, Kumaoka S, Segaloff A, Rubens RD (1977) Assessment of response to therapy in advanced breast cancer: a project of the Programme on Clinical Oncology of the International Union Against Cancer, Geneva, Switzerland. Cancer 39:1289–1294

    Article  PubMed  CAS  Google Scholar 

  19. Buzdar AU (2006) Topoisomerase IIalpha gene amplification and response to anthracycline-containing adjuvant chemotherapy in breast cancer. J Clin Oncol 24:2409–2411

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Breast Surgery, Shanghai Cancer Center, Fudan University, 399 Ling–Ling Road, Shanghai, 200032, China

    Yueyao Du, Qiong Zhou, Wenjin Yin, Liheng Zhou, Genhong Di, Zhenzhou Shen, Zhimin Shao & Jinsong Lu

  2. Department of Oncology, Shanghai Medical College, Fudan University, 399 Ling–Ling Road, Shanghai, 200032, China

    Yueyao Du, Qiong Zhou, Wenjin Yin, Liheng Zhou, Genhong Di, Zhenzhou Shen, Zhimin Shao & Jinsong Lu

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  1. Yueyao Du
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  2. Qiong Zhou
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  3. Wenjin Yin
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  4. Liheng Zhou
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  5. Genhong Di
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  6. Zhenzhou Shen
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  7. Zhimin Shao
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  8. Jinsong Lu
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Correspondence to Jinsong Lu.

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Yueyao Du and Qiong Zhou contributed equally to this study.

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Du, Y., Zhou, Q., Yin, W. et al. The role of topoisomerase IIα in predicting sensitivity to anthracyclines in breast cancer patients: a meta-analysis of published literatures. Breast Cancer Res Treat 129, 839–848 (2011). https://doi.org/10.1007/s10549-011-1694-9

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  • DOI: https://doi.org/10.1007/s10549-011-1694-9

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