Chemotherapy with or without trastuzumab.

The prognosis of pT1N0M0/stage I breast cancer has generally been considered so favourable that these patients are not routinely offered adjuvant systemic therapy. However, biological heterogeneity within pT1N0M0 dictates diverse outcomes within the subgroup. HER2 gene amplification or protein overexpression is uncommon in pT1N0M0 disease, but, when present, is clearly associated with a higher risk of recurrence. The role of anti-HER2 therapy in these patients is controversial. Few women with node-negative, small tumours were included in the adjuvant trastuzumab trials. There are no robust data on trastuzumab in this patient subset, although subgroup analyses suggest that proportional benefits are independent of T and N. With current guidelines and scheduling, committing to adjuvant trastuzumab involves concurrent chemotherapy, 1 year of treatment and potential cardiotoxicity. A further challenge with anti-HER2 therapy is the potential benefit in patients with demonstrable HER2 positivity within a predominantly HER2-negative tumour. The decision for therapy requires a yes/no answer, but HER2 status derives from a continuum of gene copy number and protein expression. The diagnostic threshold is made more complex by heterogeneity of the HER2 status within a tumour. This review focuses on available data for HER2-positive pT1N0M0 disease and explores the significance of intratumoural HER2 heterogeneity.