Background: Cognitive difficulties following treatment for breast cancer are frequently reported. Breast cancer treatments also disrupt the function of ovarian and glucocorticoid hormone systems, both of which can affect cognition. Methods: To assess the influence of glucocorticoid and ovarian disruption on cognitive dysfunction, survivors of breast cancer treated with the GnRH agonist Lupron were compared with healthy controls on their glucocorticoid response to a physiological stressor, and their performance on various measures of cognition including working memory, verbal paired associate memory, and narrative recall. Results: The results indicated no significant glucocorticoid response to the stressor in Lupron-treated survivors, while the controls showed significantly elevated cortisol levels. Cognitive testing showed a general impairment of narrative recall in breast cancer survivors relative to controls, irrespective of stress treatment. When tested on an emotional narrative, controls exposed to post-training stress showed a significant enhancement of emotional recall and a significant relationship between cortisol release and subsequent memory. In contrast, post-training stress produced no cognitive enhancement in survivors, and memory performance in this group showed no relationship to cortisol levels. Conclusions: These results suggest that a disruption of the enhancement of memory by stress may contribute to cognitive difficulties following breast cancer treatment. Copyright © 2011 John Wiley & Sons, Ltd.