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The concept of symptom clusters is relatively new in cancer patients' symptom management. This study, which spanned four cycles of chemotherapy, combined three commonly seen pre-treatment symptoms in cancer patients (i.e. sleep disturbances, fatigue and depression) into one symptom cluster, to explore the associations between pre-treatment cluster categories and longitudinal profiles of these same symptoms during chemotherapy.This was a prospective study. Seventy-six women with newly diagnosed stage I-III breast cancer, scheduled to receive at least four cycles of adjuvant or neoadjuvant anthracycline-based chemotherapy participated. Data were collected at seven time points before and during treatment. Sleep quality was measured with the Pittsburgh Sleep Quality Index. Fatigue was measured with the Multidimensional Fatigue Symptom Inventory—Short Form. Depressive symptoms were measured with the Center of Epidemiological Studies—Depression. Patients were divided into three groups based on the number of symptoms they experienced before the start of chemotherapy (i.e. no symptoms, 1-2 symptoms or all three symptoms) and a symptom cluster index (SCI) was computed.All women reported worse sleep, more fatigue and more depressive symptoms during treatment compared with baseline (allp's<0.01); however, those women with a higher SCI (i.e. more symptoms pre-treatment) continued to experience worse symptoms during treatment compared with those who began with fewer symptoms (allp's<0.01).A higher clinically relevant-based pre-treatment symptom cluster was associated with more sleep disturbances, greater fatigue and more depressive symptoms during chemotherapy. Specific interventions for these pre-treatment symptoms may improve the frequency and severity of these same symptoms during chemotherapy, when they are most severe and most disruptive to quality of life.