Incidence and Risk of CNS Mets as Site of 1st Recurrence in HER2+ BC pts. & Herceptin

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Ann Oncol. 2013 Mar 4;[Epub Ahead of Print], EM Olson, M Abdel-Rasoul, J Maly, et al

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Although adjuvant trastuzumab decreases overall risk of HER2+ breast cancer relapse, this large meta-analysis confirms that patients who do relapse have a higher incidence of brain metastases. Therefore, the use of trastuzumab has changed the natural history of the disease in this setting.

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.

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