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 1, J. Maly 1, C. S. Wu 1, N. U. Lin 2, and C. L. Shapiro 1,
1. Division of Medical Oncology, Department of Internal Medicine, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus
2. Division of Women's Cancer, Dana-Farber Cancer Institute, Boston, USA
Correspondence to: Dr. E. M. Olson, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, B407 Starling Loving Hall, 320 W. 10th Ave, Columbus, OH 43210, USA. E-mail:
erin.olson@osumc.edu
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.
Ann Oncol (2013) doi: 10.1093/annonc/mdt036 First published online: March 4, 2013
http://annonc.oxfordjournals.org/con...dt036.abstract