Distinct affective neural phenotypes in breast cancer survivors: implications for personalized supportive care after chemotherapy

Abstract Purpose Anxiety and emotional dysregulation remain among the most prevalent unmet supportive care needs in breast cancer survivorship, yet reported affective outcomes are strikingly inconsistent, with some survivors showing elevated distress and others displaying resilience or post-traumatic growth. Because distress screening in survivorship relies almost exclusively on self-report, the neural mechanisms shaping how chemotherapy-exposed survivors perceive and report emotional experience remain poorly understood, limiting mechanism-informed psychosocial support. Methods Forty female breast cancer survivors (27 chemotherapy-treated, 13 non-chemotherapy) and 30 age-matched healthy controls completed a validated face-word emotional Stroop task during functional MRI to probe emotional attention and conflict regulation. Standardized cognitive and affective questionnaires were aggregated into composite indices characterizing each survivor’s neurobehavioral profile. Results Chemotherapy-treated survivors showed poorer Stroop accuracy for faces normatively categorized as fearful and hypoactivation of the dorsomedial prefrontal cortex, yet reported lower affective symptoms than non-chemotherapy survivors, who instead showed heightened negative attentional bias and greater incongruency-related interference in the parahippocampal gyrus and insula. A normative inverse coupling between dorsal anterior cingulate cortex activation and affective symptom severity was present only in healthy controls. Conclusion Breast cancer survivors exhibit distinct neurobehavioral phenotypes with potential supportive care implications. Lower self-reported distress in chemotherapy-treated survivors paralleled reduced salience network engagement, a configuration compatible with emotional blunting rather than genuine well-being; because emotional blunting was not measured directly, this remains an interpretive hypothesis. These findings caution against relying solely on self-report screening and motivate the hypothesis that treatment-history-informed survivorship care may be beneficial—affective re-engagement strategies for chemotherapy-exposed survivors, and attention-bias modification or mindfulness-based approaches for non-chemotherapy survivors—a proposal that now requires testing in intervention trials.