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Influence of control group therapy on the benefit from dose-dense chemotherapy in early breast cancer: a systemic review and meta-analysis

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Abstract

Purpose

Results from clinical trials of adjuvant dose-dense chemotherapy in patients with breast cancer are inconsistent.

Methods

A systematic search of MEDLINE identified studies comparing the efficacy of dose-dense adjuvant chemotherapy to a standard treatment. The primary analysis included studies that used identical regimens in the experimental and control groups, but varied only dose density. A secondary analysis included studies that used either different drugs or doses in the experimental and the control groups. Hazard ratios (HRs) and 95% confidence intervals were computed for disease-free survival (DFS) and overall survival (OS) and pooled in a meta-analysis. Subgroup analyses and meta-regression explored drug schedules utilized in control groups and the influence of clinicopathologic variables on benefit from dose-dense therapy.

Results

The primary analysis included 5 studies comprising 9819 patients while the secondary analysis included 6 studies comprising 9679 patients. Dose-dense treatment significantly improved DFS (HR 0.85, p < 0.001) and OS (HR 0.86, p = 0.008) in the primary analysis. Similar results were observed in the secondary analysis. Dose-dense schedule was important primarily in studies utilizing paclitaxel every 3 weeks as the control group (interaction p = 0.04 for DFS interaction p = 0.001 for OS). A significantly greater relative magnitude of benefit was observed in pre-menopausal women and those with nodal involvement, but there was no influence of hormone receptor status on results.

Conclusions

Adjuvant dose-dense regimens improve breast cancer outcomes. It remains uncertain whether the observed benefit reflects the impact of dose density or the inferiority of paclitaxel every 3 weeks as a control group.

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Abbreviations

CALGB:

Cancer and Leukemia Group B

CI:

Confidence intervals

DFS:

Disease-free survival

ECOG:

Eastern Cooperative Oncology Group

ER:

Estrogen receptor

HER2:

Human epidermal growth factor receptor 2

HR:

Hazard ratio

OS:

Overall survival

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Division of Medical Oncology, Princess Margaret Cancer Centre and the University of Toronto, 610 University Ave, Toronto, ON, M5G 2M9, Canada

    Hadar Goldvaser, Habeeb Majeed, Domen Ribnikar, David W. Cescon & Eitan Amir

  2. Sackler Faculty of Medicine, Tel Aviv University, P.O. Box 39040, 6997801, Tel Aviv, Israel

    Hadar Goldvaser

  3. Department of Medical Oncology, Institute of Oncology Ljubljana, 2 Zaloska cesta, 1000, Ljubljana, Slovenia

    Boštjan Šeruga

  4. Translational Research Unit, Albacete University Hospital and CIBERONC, calle Francisco Javier de Moya, 02006, Albacete, Spain

    Alberto Ocaña

Authors
  1. Hadar Goldvaser
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  2. Habeeb Majeed
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  3. Domen Ribnikar
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  4. Boštjan Šeruga
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  5. Alberto Ocaña
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  6. David W. Cescon
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  7. Eitan Amir
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Corresponding author

Correspondence to Eitan Amir.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

This meta-analysis complies with the current laws.

Appendices

Appendix 1

Search algorithm

(dose-dense chemotherapy OR dense OR acceler* OR weekly OR bi-weekly OR biweekly) AND (Breast neoplasm MeSH OR ((breast OR mammary OR mamario OR seno) AND (carcinoma OR malignan* OR neoplasm OR tumor)))) AND (randomized controlled trial [pt]OR controlled clinical trial [pt]OR randomized controlled trial [mh]OR double-blind method [mh] OR single-blind method [mh] OR clinical trial [pt] OR clinical trials [mh] OR (“clinical trial”) [tw] OR singl* [tw] OR doubl* [tw] OR trebl* [tw] OR tripl* [tw] AND (mask* [tw] OR blind* [tw]))) OR comparative study [mh] OR evaluation studies [mh] OR follow up studies [mh] OR prospective studies [mh] OR control* [tw] OR prospective* [tw] OR volunteer* [tw] NOT (animals [mh] NOT humans [mh]).

Appendix 2

See Table 4.

Table 4 Subgroup for disease-free and overall survival based on generation of chemotherapy regimen in experimental and control groups
Full size table

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Goldvaser, H., Majeed, H., Ribnikar, D. et al. Influence of control group therapy on the benefit from dose-dense chemotherapy in early breast cancer: a systemic review and meta-analysis. Breast Cancer Res Treat 169, 413–425 (2018). https://doi.org/10.1007/s10549-018-4710-5

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  • DOI: https://doi.org/10.1007/s10549-018-4710-5

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