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Fatigue, insomnia and pain are some of the most common and distressing symptoms experienced during breast cancer (BC) treatment and survivorship. The symptoms have been found to impact one another and to form a symptom cluster, and greater severity of the symptoms may be negatively associated with physical and emotional functioning in survivorship. In exploratory analyses from a randomized controlled trial examining the effect of progressive resistance training on the development of lymphedema after BC, we aimed to examine the burden of the symptom cluster fatigue-pain-insomnia, and its prognostic value for long-term symptom severity as well as emotional and physical functioning Latent profile analysis was used to identify groups with similar severity of pain, fatigue and insomnia among 158 patients with BC two weeks after surgery. Mixed effects Tobit regression models were used to estimate fatigue, pain, insomnia, and physical and emotional functioning 20 weeks, 1 year and 3.5 years after surgery. Two symptom burden groups were identified: 80% of women had a low severity while 20% of women had a high severity of the three symptoms after BC surgery. 3.5 years later, the women with high symptom burden post-surgery still had higher pain, insomnia and fatigue scores than women with low symptom burden. High symptom burden post-surgery was associated with worse physical functioning 3.5 years later, while emotional functioning was only negatively impacted during the first year. These findings warrant larger studies investigating if symptom burden early in BC trajectory can be used for risk stratification for persistent symptoms and diminished physical functioning with the purpose of developing and implementing targeted interventions.