Breast cancer, one of the most frequently diagnosed malignancies among women, continues to pose a major global public health challenge. According to recent global statistics, more than 2 million new cases and approximately 680,000 breast cancer-related deaths occur annually, with projections reaching 3 million new cases and 1 million deaths by 2040 (1). Although advances in early diagnosis and treatment have led to improved survival rates, the prolonged nature of breast cancer therapy imposes considerable psychological and emotional burdens on patients. Emerging evidence indicates that, beyond the physical impact of the disease, breast cancer survivors frequently experience substantial mental health challenges, including anxiety, depression, and psychological distress throughout the course of treatment (2, 3). Cancer-related fatigue (CRF), a persistent, subjective sense of tiredness associated with cancer or its treatment, is one of the most debilitating psychological and somatic symptoms, negatively affecting patients’ cognitive function, mood, social interactions, and quality of life (4–6).

Pharmacotherapy is a cornerstone of breast cancer management and often spans years, especially for hormone receptor–positive subtypes. Sustained adherence to long-term endocrine or targeted therapies is essential for achieving favorable outcomes, including recurrence prevention and survival benefits (7). However, long-term medication use often presents adherence challenges owing to side effects, psychological distress, and treatment fatigue (8, 9). Psychological resilience and mental resources play a pivotal role in shaping patients’ medication behaviors and symptom trajectories.

Psychological capital (PsyCap), a construct rooted in positive psychology, comprises four core psychological components: self-efficacy, optimism, hope, and resilience. These internal resources have been associated with enhanced psychological adjustment, greater engagement in health-promoting behaviors, and improved emotional regulation among individuals with chronic illnesses (10). Although prior research has explored the association between PsyCap and specific cancer outcomes, little is known about its mediating role in the relationship between medication adherence and CRF among patients with breast cancer undergoing long-term pharmacotherapy.

Therefore, this study aimed to investigate the mediating effect of PsyCap on the relationship between medication adherence and CRF in breast cancer patients. By identifying this psychological pathway, we seek to offer new insights into mental health–informed interventions that could support treatment adherence and reduce psychological distress during extended pharmacological treatment.

Breast cancer is a highly heterogeneous malignant tumor with a complex pathogenesis and is often influenced by genetic factors (14). Previous studies have shown that approximately 5% of breast cancer cases are associated with BRCA1, BRCA2, and other high-penetrance gene mutations (15, 16). In recent years, treatment strategies have transitioned from single-modality approaches to multidisciplinary comprehensive care (17, 18). Beyond disease management, increasing attention has been directed toward the psychological burden experienced by patients. Studies have shown that fatigue, sleep disturbance, and psychological symptom clusters, comprising anxiety, depression, tension, irritability, sadness, and worry, are among the most common symptom clusters experienced by patients with breast cancer. Moreover, the composition and severity of these symptom clusters often vary across the different stages of cancer treatment (19). CRF is a distressing and persistent symptom prevalent across the continuum of diagnosis, treatment, and recovery, with reported incidence rates ranging from 70% to 100% (20).

Despite the availability of effective therapies, medication adherence among breast cancer patients remains suboptimal. Studies have estimated that approximately 28% of patients exhibit some level of nonadherence (21). Irregular medication use can result in sub-therapeutic drug concentrations, limiting efficacy, increasing the risk of tumor recurrence, and compromising long-term outcomes.

Psychological capital, first proposed by Luthans et al., is rooted in positive psychology and reflects an individual’s positive mental state, encompassing self-efficacy, optimism, hope, and resilience (22). While prior research has explored the relationships between PsyCap and individual health outcomes, such as fatigue, few studies have examined the mediating role of medication adherence and CRF in oncology populations. The present study addresses this gap by offering evidence that PsyCap significantly mediates the relationship between adherence and fatigue, thus providing a novel framework for intervention development.

Each PsyCap component contributes uniquely to treatment engagement and psychological resilience. Self-efficacy refers to the belief in one’s ability to execute behaviors necessary to manage illness, whereas optimism reflects a positive attributional style. Hope promotes goal-directed motivation and resilience denotes the capacity to recover from adversity (23). In this study, the mean PsyCap score among participants was 86.65 ± 8.37, reflecting a moderate-to-low level consistent with the findings of Han et al. (24). The relatively low PsyCap levels observed may stem from the emotional impact of cancer diagnosis, including fear of disease progression and physical decline, which can deplete psychological resources.

Medication adherence was also found to be moderate (5.36 ± 1.12) and likely influenced by fluctuating psychological states. Patients often show high adherence early in treatment, which is driven by hope for recovery. However, as treatment progresses, particularly in the absence of visible improvements, negative emotions, such as anxiety and despair, may reduce motivation and disrupt medication routines. Additionally, fatigue and prolonged treatment can erode medication management.

Effective pharmacological therapy suppresses tumor growth and controls disease progression. However, poor adherence disrupts this process, which leads to disease progression and increased fatigue. The mean CRF score in this study was 36.77 ± 5.98, indicating a moderate level of severity, consistent with the findings of Lapidari et al. (25). Biologically, fatigue may be driven by tumor-derived metabolites, such as cytokines and lactic acid, which disrupt neurotransmitter balance and trigger systemic inflammation. Psychologically, cancer is a major stressor. Negative coping mechanisms such as avoidance and denial may intensify emotional exhaustion and energy depletion.

Correlation analysis revealed that PsyCap was positively associated with medication adherence and negatively associated with CRF. Similarly, adherence was inversely correlated with CRF. The mediation analysis confirmed that PsyCap partially mediated the relationship between medication adherence and CRF, accounting for 55.68% of the total effect. This suggests that patients with higher PsyCap are more confident in their treatment, adhere more consistently to medication regimens, and are better equipped to manage their fatigue.

Psychological interventions that enhance PsyCap, such as psychoeducation, cognitive-behavioral strategies, and positive reinforcement, could significantly improve adherence and symptom management. The Saudi Arabian Primary Care Asthma Assessment and Management Program emphasizes the importance of early screening for psychological symptoms and treatment adherence in patients with poorly controlled asthma to prevent further deterioration of symptoms (26). Fuentes et al. (27) reported that psychological stressors negatively influenced medication adherence among Latino individuals living with HIV. Similarly, Chayadi et al. (28) demonstrated that anxiety and depression in cancer patients can exacerbate CRF. Mindfulness-based interventions for patients with cancer have been shown to alleviate psychological distress and promote physical well-being. Additionally, a study conducted in the United States (29) identified emotional symptoms, sleep disturbances, and neuromuscular fatigue as significant predictors of CRF, highlighting their relevance in developing targeted medical support strategies for patients experiencing cancer-related fatigue.

Gu et al. (30) demonstrated that increasing PsyCap improves treatment confidence and adherence. Similarly, Xin et al. (31) reported that web-based positive psychotherapy can elevate PsyCap and alleviate CRF. Interventions that foster self-efficacy, encourage hope, and cultivate resilience may help patients reframe fatigue as a temporary and manageable challenge, promoting proactive coping strategies, such as seeking support, engaging in physical activity, and practicing relaxation techniques.

These findings demonstrate a potential positive feedback cycle: elevated psychological capital contributes to improved medication adherence, which, in turn, alleviates symptom burden and further enhances psychological well-being. This highlights the need for integrative psychosocial care in oncology practice rather than focusing exclusively on pharmacological treatment or physical symptoms. It is essential for healthcare teams to systematically assess and support patients’ psychological resources throughout the course of long-term cancer treatment.

This study has several limitations. First, all participants were recruited from a single tertiary care hospital in China, which may limit the generalizability of the findings to a broader or more diverse population. Second, the relatively small sample size (n = 90) reduced the statistical power and may have introduced sampling bias. Third, its cross-sectional design precludes causal inferences. Future research should adopt a longitudinal or interventional design to confirm the mediating role of PsyCap over time. Expanding the study to include multicenter samples and diverse cultural backgrounds would enhance external validity. Third, the SR-MARS was a self-developed medication adherence scale. Although it has been applied in our clinical practice, further validation studies are needed to establish its reliability and validity.

In addition to medication adherence and CRF, the PsyCap of patients with breast cancer is influenced by multiple physiological and lifestyle factors, including dietary habits and overall physical condition. Diets high in sugar and fat have been shown to disrupt gut microbiota diversity, thereby reducing the synthesis of brain-derived neurotrophic factor (BDNF), impairing hippocampal neurogenesis, and diminishing patients’ sense of hope and cognitive control. Conversely, restrictive dieting or nutrient deficiencies, particularly inadequate intake of vitamin D and omega-3 fatty acids, can contribute to mitochondrial dysfunction, potentially leading to chronic fatigue syndrome and initiating a negative cycle of “malnutrition → fatigue → psychological exhaustion.”

Although chemotherapy can effectively delay disease progression in breast cancer, it also produces adverse effects that may undermine psychological resilience. For instance, chemotherapy-induced alopecia not only alters appearance but may also provoke catastrophic thinking related to disease progression. Additionally, estrogen depletion resulting from endocrine therapy may dysregulate serotonin transporter function, thereby triggering depressive symptoms and exacerbating psychological distress.

Clinically, integrated interventions addressing the interconnection among diet, physical health, and psychological well-being may enhance patients’ PsyCap. A multidimensional and interdisciplinary intervention framework is warranted, which combines physiological, psychological, and social support components and involves collaboration among patients, families, healthcare professionals, and broader environmental systems. Targeted cognitive behavioral therapy and mindfulness-based stress reduction techniques can help patients manage distress by fostering present-moment awareness and reducing avoidance behaviors. Nutritional plans should be tailored to individual symptoms and needs, while physical rehabilitation interventions such as manual lymphatic drainage, compression garment use, and limb function training can be employed to address physical impairments. Family involvement in treatment discussions can foster shared decision making and enhance patients perceived control. Importantly, coordinated interventions led by interdisciplinary teams, including psychologists, nutritionists, and rehabilitation therapists, are essential for ensuring the professionalism and effectiveness of PsyCap-enhancing strategies.

This study demonstrated that PsyCap partially mediates the relationship between medication adherence and CRF in patients with breast cancer. Higher PsyCap is associated with better adherence and reduced fatigue, suggesting that interventions aimed at enhancing PsyCap may serve as effective strategies for improving treatment outcomes. It is recommended that the PsyCap scale be implemented in oncology specialty clinics to facilitate baseline screening of PsyCap among newly diagnosed patients and long-term medication users. Patients identified as high risk, defined by a PsyCap score below 24, should be prioritized for intervention, and PsyCap enhancement strategies should be integrated into standard diagnostic and treatment pathways. Given the mental health challenges inherent in long-term cancer pharmacotherapy, integrating psychological support into standard oncology care may foster resilience, adherence, and overall wellbeing. Future multicenter longitudinal studies are warranted to validate and expand upon these findings.