AbstractBackgroundThere has been steadily increasing use of bilateral mastectomy (BMX) in the treatment of primary breast cancer (BC). In this study, we utilized functional magnetic resonance imaging (fMRI) to examine the influence of emotion regulation on the decision of newly diagnosed BC patients to choose BMX rather than non‐BMX treatments.MethodsWe recruited 123 women with unilateral BC, 61 of whom received BMX and 62 of whom received non‐BMX treatments, and 39 healthy controls. While participants were in the fMRI scanner, we showed them BC‐related and non‐BC‐negative images. In one condition, they were instructed to watch the images naturally. In another, they were instructed to regulate their negative emotion. We compared the fMRI signal during these conditions throughout the brain.ResultsWith non‐BC‐negative images as the baseline, BC patients showed greater self‐reported reactivity and neural reactivity to BC‐related images in brain regions associated with self‐reflection than did controls. Among the BC patients, the BMX group showed weaker activation in prefrontal emotion regulation brain regions during emotion regulation than did the non‐BMX group.ConclusionsBC patients are understandably emotionally hyper‐reactive to BC‐related stimuli and those who ultimately received BMX experience more difficulty in regulating BC‐related negative emotion than non‐BMX BC patients. These findings offer neuropsychological evidence that difficulty in managing anxiety related to the possibility of cancer recurrence is a factor in surgical treatment decision‐making and may be an intervention target with the goal of strengthening the management of cancer‐related anxiety by nonsurgical means.Trial RegistrationNCT03050463.