Background <p>This study aimed to investigate changes in depression, anxiety, fear of cancer recurrence (FCR), pain, and quality of life (QOL) over 48 months after discharge from primary treatment among breast cancer patients, and to examine the effects of different cancer treatment modalities (i.e., surgery, chemotherapy, and radiotherapy) on long-term physical and psychological outcomes and QOL.</p> Methods <p>This is a longitudinal prospective study. All participants completed a battery of questionnaires (PHQ-9, GAD-7, FCR-7, MPQ-VAS, and WHOQOL-BREF) at baseline, 12, 24, and 48 months after discharge. Long-term psychological outcomes and QOL were analyzed using a mixed model repeated measures (MMRM) approach. Group comparisons were expressed as least square (LS) mean differences with corresponding 95% confidence intervals (CIs).</p> Results <p>A total of 143 women with breast cancer were recruited for the study. The mean age was 42.27 years (SD = 7.75). The mean score of PHQ decreased from 3.50 at baseline (T1) to 1.24 at the 48-month (T4). Anxiety levels dropped from 4.09 at T1 to 2.74 at T4, FCR decreased from 21.72 at T1 to 18.70 at T4, and pain levels decreased from 12.96 at T1 to 11.50 at T4. Participants’ QOL increased from 87.77 at baseline to 93.42 at the 12-month (T2), then remained stable thereafter (T3 and T4). The LS mean difference in GAD-7 from baseline to endpoint between participants with or without mastectomy was -2.0996 (95% CI: -3.4842, -0.7150).</p> Conclusions <p>Breast cancer patients’ depression, anxiety, FCR, and pain levels showed a decreasing trend over 48 months after discharge, while patients’ QOL improved at the 12-month follow-up and remained stable throughout the study period. Patients with mastectomy experienced higher levels of anxiety than those with partial lumpectomy after 48 months post-surgery.</p>