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Do adjuvant aromatase inhibitors increase the cardiovascular risk in postmenopausal women with early breast cancer†

Meta-analysis of randomized trials

  1. Federica Cuppone MD1,‡,
  2. Emilio Bria MD1,‡,§,*,
  3. Sunil Verma MD2,
  4. Kathleen I. Pritchard MD2,¶,
  5. Sonal Gandhi MD2,
  6. Paolo Carlini MD1,
  7. Michele Milella MD1,
  8. Cecilia Nisticò MD1,
  9. Edmondo Terzoli MD1,
  10. Francesco Cognetti MD1,
  11. Diana Giannarelli MS3

Article first published online: 26 NOV 2007

DOI: 10.1002/cncr.23171

Issue

Cancer

Cancer

Volume 112, Issue 2, pages 260–267, 15 January 2008

Additional Information

How to Cite

Cuppone, F., Bria, E., Verma, S., Pritchard, K. I., Gandhi, S., Carlini, P., Milella, M., Nisticò, C., Terzoli, E., Cognetti, F. and Giannarelli, D. (2008), Do adjuvant aromatase inhibitors increase the cardiovascular risk in postmenopausal women with early breast cancer. Cancer, 112: 260–267. doi: 10.1002/cncr.23171

Author Information

  1. 1

    Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy

  2. 2

    Division of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

  3. 3

    Department of Biostatistics, Regina Elena National Cancer Institute, Rome, Italy

  1. ‡

    The first two authors contributed equally to this article.

  2. §

    Fax: (011) 390652666219

  3. Dr. Pritchard has acted as a consultant with Sanofi-Aventis, AstraZeneca, Roche, Pfizer, Ortho-Biotech, YM Biosciences, Biomira, and Novartis. She has received research funding either directly through per case funding for studies or indirectly through the National Cancer Institute of Canada Clinical Trials Group, contracted with pharmaceutical companies from AstraZeneca, YM Biosciences, Bristol-Myers-Squibb, Sanofi-Aventis, Amgen, Ortho-Biotech, Pfizer, and Novartis. She also has received honoraria from Sanofi-Aventis, AstraZeneca, Pfizer, Roche, Aegera, YM Biosciences, and Novartis and has given paid testimony for Sanofi-Aventis and AstraZeneca. She has been a member of an Advisory Committee for Sanofi-Aventis, AstraZeneca, Ortho-Biotech, Roche, Pfizer, Novartis, Aegera, and YM Biosciences

*Department of Medical Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy

  1. †

    Presented at the Annual Meeting of the European Society for Medical Oncology, Istanbul, Turkey, September 29–October 3, 2006.

Publication History

  1. Issue published online: 4 JAN 2008
  2. Article first published online: 26 NOV 2007
  3. Manuscript Accepted: 16 AUG 2007
  4. Manuscript Revised: 10 AUG 2007
  5. Manuscript Received: 11 JUL 2007

Funded by

  • Paola Muti, MD
  • Scientiphic Director, ‘Regina Elena’ National Cancer Institute, Rome, Italy

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Keywords:

  • aromatase inhibitors;
  • cardiac;
  • toxicity;
  • meta-analysis;
  • adjuvant;
  • cardiovascular;
  • breast cancer

Abstract

BACKGROUND.

Despite the advantages from using aromatase inhibitors (AIs) compared with tamoxifen for early breast cancer, an unexpectedly greater number of grade 3 and 4 cardiovascular events (CVAE) (as defined by National Cancer Institute of Canada-Common Toxicity Criteria [version 2.0] was demonstrated.

METHODS.

Phase 3 randomized clinical trials (RCTs) comparing AI with tamoxifen in early breast cancer were considered eligible for this review. The event-based risk ratios (RRs) with 95% confidence intervals (95% CIs) were derived, and a test of heterogeneity was applied. Finally, absolute differences (ADs) in event rates and the number of patients needed to harm 1 patient (NNH) were determined.

RESULTS.

Seven eligible RCTs (19,818 patients) reported CVAE results. When considering all RCTs, the AD of the primary endpoint (CVAE) between the 2 arms (0.52%), tamoxifen versus AI, was statistically significant (RR, 1.31; 95% CI, 1.07–1.60; P = .007). This translated into an NNH value of 189 patients; when only third-generation AIs were considered, the difference (0.57%) remained significant (RR, 1.34; 95% CI, 1.09–1.63; P = .0038). Thromboembolic events were significantly more frequent in the tamoxifen arm, regardless of the strategy adopted (RR, 0.53; 95% CI, 0.42–0.65; P < .0001), without significant heterogeneity (P = .21). An AD of 1.17% and an NNH value of 85 patients were observed.

CONCLUSIONS.

According to the results from this meta-analysis, the risk of grade 3 and 4 CVAEs in patients who were receiving AIs was higher compared with the risk in patients who were receiving tamoxifen, and the difference reached statistical significance. However, the AD was relatively low, and from 160 to 180 patients had to be treated to produce 1 event. Cancer 2008. © 2007 American Cancer Society.

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