OBJECTIVE: In a pilot study, participation in the Pathfinders program was associated with reductions in distress and despair and improvements in quality of life (QOL) among advanced breast cancer patients. This study explores the relationship between psychosocial resources invoked through the Pathfinders intervention and outcomes. METHODS: Advanced breast cancer patients were enrolled in a prospective, single-arm, pilot study of the Pathfinders psychosocial program. Participants met at least monthly with a licensed clinical social worker who administered the Pathfinders intervention, which focused on strengthening adaptive coping skills, identifying inner strengths, and developing a self-care plan. Longitudinal assessments over 6 months used validated instruments to assess changes in Pathfinders targets (coping, social support, self-efficacy, spirituality, and optimism) and outcomes (distress, despair, QOL, and fatigue). Multiple linear regression models examined the joint effect of average changes in target subscales on average outcome changes, adjusted for baseline outcome scores and patient characteristics. RESULTS: Participants (n=44) were: mean age 51 (SD, 12), 20% non-Caucasian, 50% college degree, and 75% married. Improvements in active coping skills, self-efficacy, and spiritual meaning/peace significantly correlated with an improvement in despair after adjustment for demographic characteristics (all P<0.05). Improvements in social support significantly correlated with positive changes in distress (P<0.05). Gains in learned optimism independently correlated with an increase in overall QOL (P<0.01). CONCLUSIONS: In this pilot assessment, changes in pre-defined Pathfinders targets such as coping skills, social support, self-efficacy, spirituality, and optimism correlated with improvements in patient-reported outcomes.