Role of HER2-neu as a prognostic factor for survival and relapse in pT1a-bN0M0 breast cancer: a systematic review of the literature with a pooled-analysis.

High levels of human epidermal growth receptor 2 (HER2) expression are associated with recurrence and death in breast cancer (BC) patients. We have performed a systematic review and meta-analysis in order to evaluate the prognosis for HER2+ pT1a-bN0M0 BC patients. A search of PubMed and Embase was performed. Studies were included if they reported hazard ratios (HRs) with a 95% confidence interval (CI) for multivariate analyses of relapse or survival in pT1a-bN0M0, HER2+ BC patients treated with surgery and chemotherapy and/or endocrine therapy, but not with trastuzumab. A total of 764 patients from seven studies were included in the meta-analysis. In the pooled analysis, HER2 had a detrimental effect on relapse-free (HR 4.68, 95% CI 3.05-7.18; p<0.00001) and distant relapse-free survival, with a HR of 5.6 (95% CI 2.65-11.85; p<0.00001). HER2+ status was also linked to increased risk of death (HR 3.4, 95% CI 0.86-13.41; p=0.08) and worst BC-specific survival (HR 2.61, 95% CI 1.51-4.51; p=0.0006), but these data were presented in few studies. HER2+ pT1a-bN0M0 BC is associated with a dismal prognosis. In these patients, HER2 has to be taken into account when deciding on adjuvant therapy, and trastuzumab should be considered.