Trastuzumab is an established treatment for patients with metastatic breast cancer who have overexpression or amplification of HER2. Several large, multicentre, randomized open-label, phase III trials—including the HERA trial—demonstrated a significant reduction of recurrence and death in patients with early stage disease with 1 year of adjuvant trastuzumab compared with observation. Whether a longer duration of trastuzumab would further improve outcome is unknown.

Now, Aron Goldhirsch and colleagues report the first results of the comparison between 1 year or 2 years of adjuvant trastuzumab, and provide updated results of the comparison of 1 year of trastuzumab versus observation. The HERA study was conducted between 2001 and 2005 and enrolled 5,102 patients with HER2-positive early stage breast cancer, and the latest data are based on 8 years of follow up. There was a highly significant advantage for the 1-year trastuzumab group compared with observation, with a 24% reduction in both the risk of recurrence and death.

Richard Gelber, biostatistician and coauthor of the study elaborates: “what makes these updated results so striking is that 52% of the patients in the control arm were selectively crossed over to receive trastuzumab after the first results of the trial were released; thus, the actual treatment benefit is probably larger than the observed treatment effect. In addition, the HERA trial was unique in that it also evaluated 2 years of trastuzumab.”

In the comparison of 1 year versus 2 years of treatment in 3,105 patients, no difference in disease-free survival (the primary end point) was shown; however, the incidence of grade 3 or 4 adverse events was higher for the 2-year arm versus the 1-year arm. Also, the percentage of patients with left ventricular ejection fraction decline was higher for those receiving 2 years of trastuzumab. The implication of these results is that 2 years of trastuzumab is not recommended—1 year of adjuvant treatment remains the standard of care for patients with HER2-positive tumours. Several ongoing studies are comparing 1 year of trastuzumab versus shorter therapy duration (6 months), and these results are anxiously awaited.