Breast cancer is the second cause of cancer mortality worldwide and there is an unmet need for novel anticancer agents. Lapatinib is a novel tyrosine kinase inhibitor for treatment of breast cancer with human epidermal growth factor receptor 2 (HER2) amplification. Given promising results in clinical studies, we investigated the survival benefits of lapatinib use in patients with HER2-overexpressing advanced or metastatic breast cancer. We searched MEDLINE, EMBASE, American Society of Clinical Oncology Meeting proceedings, San Antonio Breast Cancer Symposia proceedings, and the Cochrane Library between 2000 and 2008 for randomized controlled trials where lapatinib was used as single agent or in combination with or following other therapies. Three trials (n=704) met the inclusion criteria. Study quality was assessed by two independent reviewers and meta-analyses were conducted. Significant differences were observed between lapatinib-containing treatments to those without lapatinib in terms of survival. Pooled estimates suggested the hazard ratios of 0.61 [95% confidence interval (CI): 0.50-0.74] for progression-free survival and 0.76 (95% CI: 0.60-0.97) for overall survival. Objective response rate and clinical benefit rate also showed significant differences in favoring the use of lapatinib with odds ratios of 2.15 (95% CI: 1.48-3.11) and 2.23 (95% CI: 1.59-3.12), respectively. Heterogeneity between studies was not observed. In conclusion, addition of lapatinib to conventional anticancer treatment might offer superior survival benefit to patients with advanced metastatic HER2-overexpressing breast cancer. Further investigations on the use of lapatinib in combination with anticancer agents are warranted.

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mTOR inhibitors seemed to be potentially useful for the treatment of breast cancer with acceptable safety profile. The challenge remains the identification of suitable candidates with different phenotypes. More structured studies incorporating molecular, clinical and translational research need to be initiated. Future research on mTOR inhibitors for breast cancer should focus on the evaluation of optimal schedule, patient selection and combination strategies to maximize the use of this new class of targeted agents.