A B S T R A C T PurposeThe Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial included a prospectively planned pathology substudy testing the predictive value of progesterone receptor (PgR) expression for outcome of estrogen receptor-positive (ER-positive) early breast cancer treated with exemestane versus tamoxifen. Patients and MethodsPathology blocks from 4,781 TEAM patients randomly assigned to exemestane versus tamoxifen followed by exemestane for 5 years of total therapy were collected centrally, and tissue microarrays were constructed from samples from 4,598 patients. Quantitative analysis of hormone receptors (ER and PgR) was performed by using image analysis and immunohistochemistry, and the results were linked to outcome data from the main TEAM trial and analyzed relative to disease-free survival and treatment. ResultsOf 4,325 eligible ER-positive patients, 23% were PgR-poor (Allred Ͻ 4) and 77% were PgRrich (Allred Ն 5). No treatment-by-marker effect for PgR was observed for exemestane versus tamoxifen (PgR-rich hazard ratio [HR], 0.83; 95% CI, 0.65 to 1.05; PgR-poor HR, 0.85; 95% CI, 0.61 to 1.19; P ϭ .88 for interaction). Both PgR and ER expression were associated with patient prognosis in univariate (PgR HR, 0.53; 95% CI, 0.43 to 0.65; P Ͻ .001; ER HR, 0.66; 95% CI, 0.51 to 0.86; P ϭ .002), and multivariate analyses (P Ͻ .001 and P ϭ .001, respectively). A trend toward a treatment-by-marker effect for ER-rich patients was observed. ConclusionPreferential exemestane versus tamoxifen treatment benefit was not predicted by PgR expression; conversely, patients with ER-rich tumors may derive additional benefit from exemestane. Quantitative analysis of ER and PgR expression provides highly significant information on risk of early relapse (within 1 to 3 years) during treatment. Oncol 29:1531Oncol 29: -1538 J Clin

BackgroundSevere limb ischaemia is defined by ischaemic rest/night pain, tissue loss, or both, secondary to arterial insufficiency and is increasingly caused by infra-popliteal (below the knee) disease, mainly as a result of the increasing worldwide prevalence of diabetes. Currently, it is unknown whether vein bypass surgery or the best endovascular treatment (angioplasty or stenting) represents the optimal revascularisation strategy in terms of amputation-free survival, overall survival, relief of symptoms, quality of life and cost-effective use of health care resources.Methods/DesignThe Bypass vs. Angioplasty in Severe Ischaemia of the Leg - 2 Trial is a UK National Institute of Health Research, Health Technology Assessment funded, multi-centre randomised controlled trial that compares, at the point of clinical equipoise, the clinical and cost-effectiveness of a ‘vein bypass first’ and a ‘best endovascular treatment first’ revascularisation strategy for severe limb ischaemia due to infra-popliteal disease. The primary clinical outcome is amputation-free survival defined as the time to major (above the ankle) amputation of the trial limb or death from any cause. The primary outcome for the cost-effectiveness analysis is cost per quality-adjusted life year. Secondary outcomes include overall survival, quality of life, in-hospital mortality and morbidity, repeat and crossover interventions, healing of tissue loss and haemodynamic changes following revascularisation. Sample size is estimated at 600 patients. An economic evaluation will be conducted from the perspective of the National Health Service and comprise a ‘within-study’ analysis, based on prospectively collected trial data and a ‘model-based’ analysis, which will extrapolate and compare costs and effects beyond the study follow-up period.DiscussionThe BASIL-2 trial is designed to be pragmatic and represent current practice within the United Kingdom. Patients with severe limb ischaemia can only be randomised into the trial where clinical equipose exists. The advent of hybrid operating procedures should not be a barrier to randomisation, should a patient require inflow correction prior to tibial revascularisation.Trial registrationISRCTN:27728689 Date of registration: 12 May 2014.

Semiautomated image analysis is appropriate for the analysis of tissue biomarkers within large clinical trials. These data provide support for the use of TMAs and image analysis in translational research.