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The Kynurenine pathway (KP) represents the major degrading route of Tryptophan metabolism in humans, and has previously found to be dysregulated in various diseases including advanced breast cancer. Chronic inflammatory induced KP overactivation is linked with disease progression and poorer prognosis, while correlating with disease-related symptoms such as fatigue and depression. Therefore, manipulating the KP could be a promising target for pharmacological and non-pharmacological interventions in order to counteract advanced breast cancer pathophysiology and disease related-symptoms. In previous RCT’s we already have shown that physical exercise manipulates the KP in healthy subjects and clinical populations including persons with breast cancer. In detail, regular physical exercise is suspected to dampen a pathophysiological over activation of the KP while shifting it towards the neuroprotective kynurenic acid. On the basis of already collected biomaterial of an EU Horizon 2020 funded multicenter two arm randomized controlled trial (n = 357), investigating the impact of a multimodal six-month exercise program in patients with advanced breast cancer, our research should serve for an in-depth analysis of the KP as one underlying pathophysiological process. This translational approach aims to fill the gap between basic mechanistic and patient-orientated factors in the field of exercise oncology and provide evidence for exercise based treatment to address the wide-spread impact on patients disease-symptoms, -progress and -outcome.