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The relationship between time to initiation of adjuvant chemotherapy and survival in breast cancer: a systematic review and meta-analysis

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Abstract

Background

It is known that adjuvant chemotherapy improves survival in women with breast cancer. It is not known whether the interval between surgery and the initiation of chemotherapy influences its effectiveness.

Purpose

To determine the relationship between time to initiation of adjuvant chemotherapy and survival in women with breast cancer, through a systematic review of the literature and meta-analysis.

Methods

Systematic review of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Database of Controlled Trials, Google Scholar, and abstracts presented at major international oncology conferences. The primary meta-analysis included only high-validity studies which directly measured the time from surgery to initiation of adjuvant chemotherapy and which controlled for major prognostic factors. Outcomes reported in the original studies were converted to a regression coefficient (β) and standard error corresponding to a 4-week delay in the initiation of chemotherapy. These relative risks were combined in both fixed- and random-effects models. Homogeneity was assessed by the Cochran χ 2 statistic and the I 2 statistic. Potential publication bias was investigated using standard error-based funnel plots.

Results

Meta-analysis of 8 high-validity studies demonstrated that a 4-week increase in TTAC was associated with a significant increase in the risk of death in both the fixed-effects model (RR 1.04; 95 % CI, 1.01–1.08) and random-effects model (RR 1.08; 95 % CI, 1.01–1.15). The association remained significant when the most highly weighted studies were sequentially removed from this analysis, and also when additional, lower validity studies were included in this analysis. Funnel plots showed no significant asymmetry to suggest publication bias.

Conclusions

Increased waiting time from surgery to initiation of adjuvant chemotherapy is associated with a significant decrease in survival. Avoidance of unnecessary delays in the initiation of adjuvant chemotherapy has the potential to save the lives of many women with breast cancer.

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Funding

Dr Booth holds a Canada Research Chair in Population Cancer Care.

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Authors and Affiliations

  1. Division of Cancer Care and Epidemiology, Queen’s University Cancer Research Institute, Queen’s University, 10 Stuart Street, Level 2, Kingston, ON, K7L 3N6, Canada

    Michael J. Raphael, James J. Biagi, Weidong Kong, Christopher M. Booth & William J. Mackillop

  2. Department of Medicine, University of Toronto, Toronto, Canada

    Michael J. Raphael

  3. Department of Oncology, Queen’s University, Kingston, Canada

    James J. Biagi, Mihaela Mates, Christopher M. Booth & William J. Mackillop

  4. Department of Public Health Sciences, Queen’s University, Kingston, Canada

    Christopher M. Booth & William J. Mackillop

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  1. Michael J. Raphael
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Correspondence to William J. Mackillop.

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Conflict of interest

In 2009, Dr Mackillop provided expert testimony on the relationship between delays in post-lumpectomy radiotherapy for breast cancer and the risk of local recurrence, in a class action lawsuit in Quebec (Cilinger v Centre Hospitalier de Chicoutimi). No other disclosures.

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Raphael, M.J., Biagi, J.J., Kong, W. et al. The relationship between time to initiation of adjuvant chemotherapy and survival in breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat 160, 17–28 (2016). https://doi.org/10.1007/s10549-016-3960-3

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  • DOI: https://doi.org/10.1007/s10549-016-3960-3

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