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Among patients with cancer, the management of depression is very important to improve quality of life as well as distress. Because the efficacy of escitalopram, a potent serotonin reuptake inhibitor, has not been well evaluated in cancer patients, we investigated its effects on depression and quality of life in outpatients with breast cancer.A 12-week, open-label, prospective study with escitalopram (5–20 mg/day) was performed in 79 breast cancer outpatients with depression. The primary outcome was measured using the Hamilton Depression Rating Scale (HAMD), which was administered at baseline, 1, 2, 4, 8, and 12 weeks after treatment. The Functional Assessment of Cancer Therapy-Breast (FACT-B), MD Anderson Symptoms Inventory (MDASI), Clinical Global Impression-Severity of Illness (CGI-S), and Distress Thermometer (DT) were also used to measure improvement in symptoms, distress, and quality of life.Compared to baseline, HAMD, DT, and CGI-S scores were significantly decreased at week 1 and onwards, and FACT-B and MDSAI were improved at week 2 and onwards. At the end point (week 12), all FACT-B subscales including the physical, emotional, social/family, functional well-being, and the breast cancer subscales were improved. Improvement in distress and quality of life was associated with a reduction in depressive symptoms. Of all participants, 45.1% met the response criterion (at least a 50% decrease in HAMD total score), and 30.6% met the remission criterion (HAMD total score ≤ 7) at week 12.In the present study, escitalopram improved quality of life and reduced depression in breast cancer patients. Symptoms rapidly improved within 1 week, influencing quality of life. Escitalopram may be an effective treatment of depressive symptoms in breast cancer patients.