Methods The Tamoxifen Exemestane GSK461364 mouse Adjuvant Multinational (TEAM) phase 3 trial was conducted in hospitals in nine countries. Postmenopausal women

(median age 64 years, range 35-96) with hormone-receptor-positive breast cancer were randomly assigned in a 1:1 ratio to open-label exemestane (25 mg once a day, orally) alone or following tamoxifen (20 mg once a day, orally) for 5 years. Randomisation was by use of a computer-generated random permuted block method. The primary endpoint was disease-free survival (DFS) at 5 years. Main analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, NCT00279448, NCT00032136, and NCT00036270; NTR 267; Ethics Commis;ion Trial 27/2001; and UMIN, C000000057.

Findings 9779 patients were assigned to sequential treatment (n=4875) or exemestane alone (n=4904), and 4868 and 4898 were analysed by intention to treat, respectively. 4154 (85%) patients in the sequential group and 4186 (86%) in the exemestane alone group were disease free at 5 years (hazard ratio 0.97, 95% CI 0.88-1.08; p=0.60). In the safety analysis, sequential treatment was associated with a higher incidence of gynaecological symptoms (942[20%] of 4814 vs 523 [11%] of 4852), venous thrombosis (99 [2%] vs 47 [1%]), and endometrial

abnormalities (191 [4%] vs 19 [<1%]) than was exemestane alone. Musculoskeletal adverse events (2448 [50%] vs 2133 [44%]), hypertension (303 [6%] vs 219 [5%]), and hyperlipidaemia (230 [5%] vs 136 [3%]) were reported more frequently with exemestane alone.

Interpretation Treatment regimens of exemestane alone or after tamoxifen

might CHIR98014 in vitro be judged to be appropriate options for postmenopausal women with hormone-receptor-positive early breast cancer.”
“Stress effects on learning and memory are widely recognized, but less agreement exists on whether they are positive or negative as well as on their neuronal and neuromolecular correlates. Stress involves expression of certain genes such as neurotrophin BDNF (brain derived neurotrophic factor), which is also involved in learning, but results are not consistent. Here effects of stress on memory and BDNF expression were studied using on adult male rats exposed to “”immobilization stress”" for various “”short”" durations, i.e.. 1-h, 3-h, 5-h and Acyl CoA dehydrogenase “”long-term”" ones (2-h/day for 1 week). Learning and memory was measured using passive avoidance testing (STL = step-through-latency scores) as well as plasma corticosterone (CSt) levels and hippocampal BDNF gene expression. CSt increased in the 3-h and longer stressed groups but differences were significant in the 5-h and 1-week stressed subgroups. Three and 5-h of stress markedly and significantly (60-69%, p < 0.01) decreased memory retention in the stressed animals, while 1-h of stress had no effect; prolonged stress (2-h daily for 1-week) increased memory significantly (33%. p < 0.05).