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Exercise training is thought to play a protective role against cancer development and metastasis, either by reducing hormonal stimulation of hormone-dependent cancers or by reducing the permeability of vascular walls towards invading metastatic cells. The purpose of this work was to evaluate the role of long-term exercise training in the development and metastasis of breast cancer, in an immune-competent 1-methyl-1-nitrosourea (MNU) induced rat model. A single MNU dose was administered to Sprague-Dawley rats at 50 days of age and the rats were subjected to exercise training on a treadmill at 20 m/min, 60 min/day, 5 days/week for 35 weeks. Exercised animals developed slightly less (2.30 ± 1.42) tumours per animal than sedentary animals (2.55 ± 1.44) and did not develop any metastasis, while two pulmonary metastases were observed in the sedentary group. All primary neoplasms and their metastases were positive for oestrogen ( ER) α and progesterone ( PR) receptors, indicating high hormonal sensitivity. Interestingly, exercise training increased circulating oestrogen levels, thus suggesting that the mechanism might involve either or both of a protective hormone-independent effect and modulation of tumoural vascularization. [ABSTRACT FROM AUTHOR]