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

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.

• Authors: E M Olson, M Abdel-Rasoul, J Maly, C S Wu, N U Lin, C L Shapiro
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 24 Issue 6 Pg. 1526-33 (Jun 2013) ISSN: 1569-8041 [Electronic] England
• PMID: 23463626 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab

Topics

• Antibodies, Monoclonal, Humanized (adverse effects)
• Breast Neoplasms (drug therapy, epidemiology, genetics)
• Central Nervous System Neoplasms (chemically induced, epidemiology, secondary)
• Chemoradiotherapy, Adjuvant (adverse effects)
• Female
• Humans
• Incidence
• Neoplasm Recurrence, Local (chemically induced, genetics, secondary)
• Randomized Controlled Trials as Topic (methods)
• Receptor, ErbB-2 (genetics)
• Risk Factors
• Trastuzumab
• Treatment Outcome