72 Pritchard. The Independent Data Monitoring Committee will decide when the data will be released. The ﬁnal analysis will be performed after the expected total number of DFS events have occurred. This is anticipated to be 7 years after the start of the study, following an accrual period of about 2 years and a minimum of 5 years of fur- ther follow-up. There are two planned interim analyses, scheduled to occur after one third and subsequently after two thirds of the maximum number of events have been observed. The interim analyses will be conducted after 320 and 639 events, respectively, have been recorded. In addition, analyses of secondary end points will be con- ducted at the interim time points. FACE is powered to detect a 3.5% absolute difference between the two treatment arms in DFS at 5 years. The 3.5% difference corresponds to a hazard ratio of 0.83 in favor of letrozole, corresponding to 5-year DFS values of 80.0% and 76.5% for letrozole and anastrozole, respectively. Safety end points General patient safety and drug tolerability will be evalu- ated. Adverse events are recorded at every visit and graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. A checklist of adverse events is used to solicit adverse event infor- mation from patients. Safety analyses speciﬁcally include cardiovascular events and bone fracture events. All patients are evaluated clinically for osteoporosis and fracture risks. Bone mineral density testing is recommended at least every 2 years for all patients during study therapy by dual X-ray absorpti- ometry, peripheral dual X-ray absorptiometry, or ultrasound densitometry. Osteoporosis may be managed as clinically indicated using calcium supplements, vitamin D, or bisphosphonates. Measurements of fasting serum lipids are obtained at 6 and 12 months and then annually there- after for the duration of the study treatment. Other laboratory assessments include hematology and blood chemistry. Other head-to-head studies Other trials that are directly comparing AIs are also under way. A randomized phase III trial [31] is comparing neo- adjuvant therapy with exemestane, letrozole, or anastrozole in postmenopausal women undergoing surgery for stage II or stage III breast cancer. Another ongoing randomized trial, MA.27 [32], has been designed to compare the event- free survival of postmenopausal women with HR+ primary 123 Breast Cancer Res Treat (2007) 105:67–74 breast cancer when treated with exemestane or anastrozole. Results from these trials and ongoing pharmacogenomic studies [26] will also help individualize AI therapy for early breast cancer. The study of inherited genetic polymorphisms that affect drug response and toxicity promises to help physicians individualize hormone treatment. For example, ‘‘slow metabolizers’’ of tamoxifen may have a worse outcome in the adjuvant setting with tamoxifen treatment than ‘‘fast metabolizers,’’ suggesting that these patients might be better treated with an AI [33–35]. Polymorphisms in tamoxifen metabolizing cytochrome P (CYP) 2D6 gene affect the plasma concentration of tamoxifen active metabolites: women with the CYP2D6 *4/*4 or wt/*4 genotype could have lower beneﬁt of tamoxifen treatment and tend to have a higher risk of disease relapse [35, 36]. Genetic polymorphisms in the aromatase gene, CYP19, have recently been characterized [37]. Eighty-eight poly- morphisms were identiﬁed, resulting in 44 haplotypes. Functional genomic studies revealed that polymorphisms may lead to changes in aromatase activity and altered afﬁnity for AIs. These ﬁndings indicate that genetic vari- ation in CYP19 might contribute to variation in the pathophysiology of estrogen-dependent disease. Clinical trials have been initiated to study the impact of genetic differences on response to AI therapy and may eventually lead to patient-speciﬁc selection of therapy based on opti- mizing efﬁcacy and toxicity. Conclusions Letrozole and anastrozole have both demonstrated superior efﬁcacy compared with tamoxifen as initial therapy for early breast cancer [3, 4]. Preclinical and clinical evidence suggests that AIs do not have identical pharmacodynamic proﬁles, but it is not known whether one agent may be more effective as adjuvant therapy for early breast cancer. Differences in potency in preclinical studies, and the reduction in distant metastases in the BIG 1-98 study, suggest the potential for clinical efﬁcacy differences between AIs. Based on the results of these trials, interna- tional guidelines now recommend adjuvant hormone therapy with an AI [9, 25] in patients with an increased risk of early recurrence. The FACE trial is addressing an important medical question in the oncology community: whether or not letrozole offers greater clinical beneﬁt to postmenopausal women with HR+ early breast cancer at increased risk of early recurrence compared with anas- trozole. Results from the FACE trial may reﬁne the treatment strategies for treating breast cancer in postmen- opausal women.