70 expression (see Table 1). The guidelines state that endo- crine therapy with an AI is a recommended option for patients with node-positive tumors who are in the inter- mediate- or high-risk groups. As high-risk patients are at greater risk of relapse, a drug speciﬁcally effective in this patient population would provide the oncology community with valuable information that may alter the outcomes of these patients. Is one AI superior in early breast cancer? Microarray analysis was used to study the effects of vari- ous hormone therapies on ER+ MCF-7 cells, stably transfected with the aromatase gene (MCF-7aro cells) [26]. The study found that hormonal stimulation of gene expression can be counteracted by treatment with AIs (le- trozole and anastrozole) and an anti-estrogen (tamoxifen), but that each agent had its own unique effects on gene expression (see Fig. 1), suggesting possible differences between letrozole and anastrozole [26]. Although differ- ences between letrozole and anastrozole have been demonstrated in preclinical models, it is widely recognized that preclinical ﬁndings do not always translate into clinical results, and that comparisons in one treatment setting or subpopulation cannot be extrapolated to another. A pro- spective trial is therefore needed to address the question of whether one AI is superior to another. FACE was designed to test whether there is a preferable AI for the adjuvant treatment of postmenopausal women with HR+ and lymph node-positive cancer [27]. Node- positive patients were selected, because this population has a higher risk of relapse, and recurrence events occur earlier than in node-negative patients [20, 28, 29]. Thus, Breast Cancer Res Treat (2007) 105:67–74 conducting the FACE trial in patients with lymph node- positive early breast cancer will provide an answer more quickly than conducting a trial in a broader population that includes patients with node-negative tumors. FACE trial design FACE is a phase IIIb open-label, randomized, multicenter trial [30]. The primary objective of the trial is to compare DFS at 5 years for letrozole and anastrozole. Secondary objectives are to assess safety, OS, time to distant metas- tases, and time to contralateral breast cancer [27]. Patients The trial is recruiting 4,000 patients from up to 250 international sites. Eligible patients are postmenopausal women with HR+ and lymph node-positive tumors who have recently undergone surgery for primary breast cancer (pathologic or clinical stage IIA, IIB, or IIIA). All patients must provide written informed consent. HR+ tumors are deﬁned as tumors with any detectable ER or PgR expression by institutional standards. Patients who are PgR+ and ER– are eligible for the trial. Pathologic assessment of axillary lymph nodes is determined by sen- tinel node biopsy and/or axillary lymph node dissection. Patients are stratiﬁed according to the number of involved lymph nodes and HER2 tumor status. Adjuvant trast- uzumab is permitted in patients with HER2+ tumors. Other inclusion criteria include World Health Organization per- formance status of 0 or 1, lipid panel (fasting total cholesterol and triglycerides) £ grade 1 (National Cancer Table 1 Risk categories for early breast cancer according to the St. Gallen Guidelines. Reprinted from [25], with permission from the European Society for Medical Oncology HER2 human epithelial growth factor receptor 2 pT pathological tumor size (i.e. size of the invasive component) 123 Low risk Intermediate risk High risk Steroid hormone receptors expression, node-negative, and all of the following features: pT £ 2 cm Grade 1 No peritumoral vascular invasion HER2/neu gene neither overexpressed nor ampliﬁed Age ‡35 years Node-negative and at least one of the following features: pT [ 2 cm Grade 2–3 Peritumoral vascular invasion HER2/neu gene either overexpressed or ampliﬁed Age \ 35 years Node positive (1–3 involved nodes) and HER2/neu gene neither overexpressed nor ampliﬁed Node positive (1–3 involved nodes) and HER2/neu gene either overexpressed or ampliﬁed Node-positive (4 or more involved nodes)