The ALTERNATE trial: assessing a biomarker driven strategy for the treatment of post-menopausal women with ER+/Her2- invasive breast cancer.

The Alliance for Clinical Trials in Oncology cooperative group has designed a phase III neoadjuvant clinical trial (ALTERNATE trial) which randomizes women with cT2-4 N0-3 M0 ER+/Her2- invasive breast cancer to either anastrozole, fulvestrant or its combination to assess a biomarker-driven treatment strategy to identify women with a low risk of disease recurrence. This strategy incorporates the findings that: higher expression of the proliferation marker, Ki67, after 2 weeks of neoadjuvant endocrine therapy (ET), is associated with poor recurrence-free survival, and that patients with surgical findings of pT1/2, pN0 disease, Ki67 ≤2.7% and ER Allred score of 3-8 after neoadjuvant ET have extremely low recurrence rates. We present a description and rationale for the design of this trial.