Research in context
Evidence before this study
We searched PubMed for randomised clinical trials published in English between Jan 1, 2000, and March 1, 2013, assessing long-term outcomes (>5 years' follow-up) from randomised trials of systemic therapy in patients with early breast cancer confirmed as HER2-positive, using the search terms “adjuvant”, “breast”, “randomised”, and “HER2”. We found no data in the published literature providing 10 years or more of follow-up from the use of adjuvant trastuzumab within a randomised trial.
Added value of this study
To our knowledge, this 11-year follow-up of the HERA trial provides the longest survival data of any trial that assessed the addition of anti-HER2 therapy to standard treatment for HER2-positive early breast cancer. We provide long-term patient outcome data to support the use of 1 year of adjuvant trastuzumab in this patient population, with evidence that those patients randomly assigned to receive trastuzumab (in both the 1-year and 2-years groups) sustained relative reductions in recurrence and breast cancer deaths, with the reassurance that the rate of serious toxicity does not increase over time. We also showed no evidence of a benefit of 2 years of trastuzumab compared with 1 year, and could not identify a subgroup of patients studied in the HERA trial who would not have derived long-term benefits.
Implications of all the available evidence
Patients with HER2-positive early breast cancer who meet the criteria for the HERA trial (or the other studies reported elsewhere), including the cardiac disease criteria, we believe should be offered 1 year of adjuvant trastuzumab as part of standard of care. Patients can be reassured that there are benefits in terms of better disease-free and overall survival that are sustained to at least 10 years after diagnosis, with no evidence of significant differential benefit by disease characteristics, such as nodal status or tumour hormone receptor status. Additionally, there is no evidence of late emergent side-effects, including no evidence of more cardiac endpoints emerging up to 10 years after treatment.