Metastatic breast cancer (MBC) is considered incurable. Trastuzumab (T), a monoclonal antibody that blocks HER-2 is used in combination with other chemotherapies or as monotherapy to treat various stages of breast cancer, including MBC. The aim of this study was to evaluate the safety of T as first line treatment or after progression in women with MBC.

We conducted a systematic review of randomized controlled trials. We searched the databases: MEDLINE (Pubmed), LILACS, Cochrane Library and EMBASE (accessed November 2016) and performed manual search. The methodological quality assessment was performed using the Cochrane Collaboration risk of bias tool. We adopted the random effects model for meta-analysis. The results were presented as relative risk (RR) with 95% confidence intervals.

The search retrieved 2,238 publications. After eligibility criteria assessment we included five studies on T in the first line treatment (T n = 493; no-T n = 492) and two studies on T after progression (T n = 226; no-T n = 226). In general, studies presented moderate quality. Five were funded by the pharmaceutical industry. Regarding first line treatment, the group of patients that used T had three times higher risk of developing cardiac adverse event compared to the group that did not use T (RR = 3.3; 95% CI: 1.52 − 7.29; I2 = 0%, p = 0.39). The continuity of T after progression revealed no difference between the groups regarding the risk of developing cardiac adverse event (RR = 5.31; 95% CI: 0.62 − 45.49; I2 = 0%, p = 0.62).

The evidence regarding the higher risk of cardiac adverse event with T as first line treatment for MBC is robust and this should be taken into account when balancing risks and benefits of treatment. The evidence for continuation of T after MCB progression is week and more studies are needed to confirm the findings.