Models of neurobiological systems linking personality, motivation, and emotion can be integrated with the expectancy construct to suggest hypotheses about distress and giving up in response to adversity. In 220 women with breast cancer, threat responsiveness-sensitivity of the behavioral inhibition system (BIS)-and incentive responsiveness-sensitivity of the behavioral activation system (BAS)-and expectancies about cancer recurrence were measured. It was predicted and found that high BIS sensitivity interacted with recurrence expectancy to predict elevated distress and disengagement. Low BAS sensitivity (reward responsiveness) also interacted with expectancy of recurrence to predict elevated disengagement. In contrast, high BAS sensitivity (fun seeking) interacted with recurrence expectancy to predict elevated distress. Discussion centers on theoretical implications and possible applications.