Incidence and risk of central nervous system (CNS) metastases as a site of first recurrence in patients (pts) with HER2-positive (HER2+) breast cancer treated with adjuvant trastuzumab (T).

Abstract

609 Background: T is the mainstay of adjuvant therapy in pts with HER2+ breast cancer. CNS disease as the site of first relapse after exposure to adjuvant T has been reported, although the overall incidence and relative risk (RR) of this remains unclear. We performed an up-to-date meta-analysis to determine the risk of CNS metastases as the first site of recurrence in pts with HER2+ breast cancer who received adjuvant T. Methods: Pubmed databases were searched for articles from 1966 to 2011. Abstracts presented at the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium were also searched for relevant clinical trials. Eligible studies include randomized trials with adjuvant T administered for 1 year in pts with HER2+ breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the summary incidence, RR, and 95% CIs using fixed effects inverse variance models. Results: A total of 9,020 pts were included. The incidence of CNS metastases as first site of disease recurrence in HER2+ pts receiving adjuvant T was 2.56% (95% CI 2.07% to 3.01%) compared to 1.94% (95% CI: 1.54% to 2.38%) in HER2+ pts who did not receive adjuvant T. The RR of CNS as first site of relapse in T-treated pts was 1.35 (95% CI 1.02 to 1.78, p=0.038) compared with control arms without T therapy. In subgroup analyses, there was no significant difference in CNS incidence or risk between pts treated with concurrent versus sequential T (p=0.29), weekly versus every 3 week T (p=0.56), and no difference in the T groups between studies due to median follow up time in years (p=0.68). No evidence of publication bias was observed (Q=1.78; P=0.62; I2 = 0.0%). Conclusions: This is the largest report to date demonstrating that adjuvant T is associated with an increased risk of CNS metastases as a site of first recurrence in HER2+ breast cancer pts.