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Background: Cancer-related pain is highly prevalent among outpatients with metastatic breast cancer affecting their health-related quality of life (HRQoL). This study evaluates potential effects of comprehensive pharmacologic cancer pain therapy (CPT) on HRQoL. Patients and Methods: 52 outpatients with metastatic breast cancer undergoing palliative chemotherapy participated. 28 patients suffering from moderate to severe cancer pain were offered CPT. 13 patients participated (intervention group), and 15 declined participation (control group). HRQoL was assessed with the Quality of Life Questionnaire (EORTC QLQ-C30) and the breast module QLQ-BR23 at baseline and after 3 weeks. Results: At baseline, 83% of the patients experienced cancer-related pain, of whom 35% were not prescribed any pain medication. HRQoL of all patients was reduced compared to reference scores. After CPT, the intervention group reported significantly alleviated pain and improvement in several HRQoL subscales (Global QoL, Emotional Functioning, Physical Functioning, Future Perspective, Sleeplessness). The control group did not change significantly. Conclusion: This study emphasizes the demand for sufficient pain management in palliative breast cancer outpatients. The combination of CPT as a guidance for the pharmacological aspects of cancer pain management and the EORTC QLQ-C30 as an assessment and surveillance tool appears to be a method that warrants further research.