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Meta-Analysis
. 2013 Jun;24(6):1526-33.
doi: 10.1093/annonc/mdt036. Epub 2013 Mar 4.

Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab

E M Olson  1 , M Abdel-Rasoul, J Maly, C S Wu, N U Lin, C L Shapiro
Affiliations
Meta-Analysis

Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab

E M Olson et al. Ann Oncol. 2013 Jun.

Abstract

Background: Central nervous system (CNS) disease as the site of first relapse after exposure to adjuvant trastuzumab has been reported. We carried out comprehensive meta-analysis to determine the risk of CNS metastases as the first site of recurrence in patients with HER2-positive breast cancer who received adjuvant trastuzumab.

Methods: Eligible studies include randomized trials of adjuvant trastuzumab administered for 1 year to patients with HER2-positive breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the incidence, relative risk (RR), and 95% confidence intervals (CIs) using fixed-effects inverse variance and random-effects models.

Results: A total of 9020 patients were included. The incidence of CNS metastases as first site of disease recurrence in HER2-positive patients receiving adjuvant trastuzumab was 2.56% (95% CI 2.07% to 3.01%) compared with 1.94% (95% CI 1.54% to 2.38%) in HER2-positive patients who did not receive adjuvant trastuzumab. The RR of the CNS as first site of relapse in trastuzumab-treated patients was 1.35 (95% CI 1.02-1.78, P = 0.038) compared with control arms without trastuzumab therapy. The ratio of CNS metastases to total number of recurrence events was 16.94% (95% CI 10.85% to 24.07%) and 8.33% (95% CI 6.49% to 10.86%) for the trastuzumab-treated and control groups, respectively. No statistically significant differences were found based on trastuzumab schedule or median follow-up time. No evidence of publication bias was observed.

Conclusions: Adjuvant trastuzumab is associated with a significant increased risk of CNS metastases as the site of first recurrence in HER2-positive breast cancer patients.

Keywords: breast cancer; central nervous system; hER2; meta-analysis; metastases; trastuzumab.

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Figures

Figure 1.
Figure 1.
Selection process for the randomized, controlled trials included in the meta-analysis.
Figure 2.
Figure 2.
Relative risk (RR) of central nervous system (CNS) recurrence events as a site of first relapse associated with adjuvant trastuzumab versus control among patients with HER2-positive breast cancer.
See this image and copyright information in PMC

References

    1. Perez EA, Romond EH, Suman VJ, et al. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011;29:3366–3373. - PMC - PubMed
    1. Perez EA, Suman VJ, Davidson NE, et al. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011;29:4491–4497. - PMC - PubMed
    1. Gianni L, Dafni U, Gelber RD, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011;12:236–244. - PubMed
    1. Spielmann M, Roché H, Delozier T, et al. Trastuzumab for patients with axillary-node–positive breast cancer: results of the FNCLCC-PACS 04 Trial. J Clin Oncol. 2009;27:6129–6134. - PubMed
    1. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Eng J Med. 2011;6:1273–1283. - PMC - PubMed

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