Background:Patients underwent a compression (sleeve and gauntlet) intervention for subclinical breast cancer-related lymphedema (S-BCRL). Physical, emotional, and quality-of-life (QoL) outcomes were examined. Associations of change in extracellular fluid alone through bioimpedance spectroscopy (BIS) or change in whole-arm volume through tape measure with the outcomes at time of S-BCRL were explored.Methods and Results:We enrolled newly diagnosed nonmetastatic breast cancer patients for surveillance up to 36 months postoperatively. Upon detection of S-BCRL, a 28-day compression intervention was initiated. Data were obtained through physical examination/measurement and self-report instruments: skin examination, Lymphedema Symptom Intensity and Distress Survey-Arm, and Functional Assessment of Cancer Therapy General (FACT-G), Breast (FACT-B), and FACT-B+4.Improvements with intervention were observed in the proportion of patients reporting symptom scores ≥3 in function (Cohen'sd= −0.46,p< 0.01), in biobehavioral (Cohen'sd= −0.30,p< 0.05), maximum number of skin conditions (Cohen'sd= −0.34,p< 0.05. 3), FACT-B (Cohen'sd= 0.52,p< 0.01), and FACT-B + four (Cohen'sd= −0.42,p< 0.01). At the study endpoint, compared with those who did not progress, chronic breast cancer-related lymphedema (C-BCRL) progressing patients had higher overall symptom scores (p= 0.037), more skin conditions (p= 0.009), and lower total FACT-G and FACT-B scores (p< 0.05). At the time of S-BCRL, detection of greater BIS unit change correlated with higher symptom, skin condition, and QoL values. Greater whole-arm volume change correlated with higher FACT-B+4 scores (allp< 0.05).Conclusions:Prospective surveillance, symptom assessment, and compression intervention promote low progression rates from S-BCRL to C-BCRL and as such reduce symptom burden. This closed study is registered withClinicalTrials.govNCT02167659