Breast Cancer Research and Treatment

, Volume 135, Issue 2, pp 335–346 | Cite as

Mortality, leukemic risk, and cardiovascular toxicity of adjuvant anthracycline and taxane chemotherapy in breast cancer: a meta-analysis

  • Fausto Petrelli
  • Karen Borgonovo
  • Mary Cabiddu
  • Veronica Lonati
  • Sandro Barni
Review

Abstract

The contribution of adjuvant taxanes (T) in cardiovascular toxicity, leukemic risk, and non-cancer-related deaths is unknown when they are added to anthracycline (A)-based chemotherapy for breast cancer. We performed a meta-analysis of published randomized controlled trials (RCTs) to determine the risk of cardiovascular toxicity, leukemia, neurotoxicity, and non-breast cancer-related mortality associated with T added to adjuvant A in breast cancer. PubMed was searched to identify relevant studies. Eligible studies included prospective RCTs in which approved T in combination with A (A + T) were compared with A alone as adjuvant chemotherapy for breast cancer. Summary incidence rates, relative risks (RRs), and 95 % confidence intervals were calculated by means of fixed- or random-effects models. A total of 27,039 patients from 15 RCTs were included. Compared with A alone, A + T was associated with a statistically similar risk of toxicity. Compared with control arms, A + T schedules with less cumulative dose of anthracyclines than control arms were associated with lower severe cardiotoxicity (RR = 0.41, [95% CI 0.26–0.66], P = 0.0002), venous thromboembolic events (RR 0.45, [95% CI 0.26–0.79], P = 0.006), and leukemic risk (RR 0.39; [95%CI 0.18–0.87] P = 0.02), but with an increased risk of non-breast cancer-related mortality (RR = 1.79, [95% CI 1.06–3.04] P = 0.03). In particular, this risk of death is greater when >3 cycles of A precede T in sequential schedules (RR 2.24, [1.2–4.21] P = 0.01). This meta-analysis suggests that A + T-based adjuvant chemotherapy is as toxic as A alone with no significant difference in non-breast cancer-related mortality. However, sequential A + T schedules are associated with less toxicity, but a significant increase in non-breast cancer-related mortality compared with control arms with a greater dose of A.

Keywords

Breast cancer Adjuvant chemotherapy Anthracyclines Taxanes Cardiotoxicity 

Supplementary material

10549_2012_2121_MOESM1_ESM.doc (36 kb)
Supplementary material 1 (DOC 35 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Fausto Petrelli
    • 1
  • Karen Borgonovo
    • 1
  • Mary Cabiddu
    • 1
  • Veronica Lonati
    • 1
  • Sandro Barni
    • 1
  1. 1.Department of Medical and Surgical Oncology, Division of Medical OncologyAzienda Ospedaliera Treviglio-CaravaggioTreviglioItaly

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