Baduanjin exercise for menopausal symptoms in breast cancer patients on aromatase inhibitors: a randomized controlled pilot study

Introduction

Breast cancer is the most prevalent malignancy among women globally and the leading cause of cancer-related morbidity in China [1]. Advances in multimodal therapies, including surgery, endocrine therapy, and targeted treatments, have significantly improved survival rates, particularly for hormone receptor-positive cases, which constitute over 50 % of diagnoses [2], [3], [4]. Aromatase inhibitors, as a core treatment modality for adjuvant endocrine therapy in postmenopausal hormone receptor-positive breast cancer patients, reduce the overall recurrence risk by 27 % compared with no extended treatment after the initial 5-year therapy, underscoring their long-term recurrence prevention value [5]. However, their clinical benefits are negated by a high discontinuation rate (36.9 % within five years) due to treatment-emergent adverse effects such as arthralgia, vasomotor symptoms, and fatigue, which impair quality of life and increase mortality risk among non-adherent patients [6], 7].

Non-pharmacological interventions, particularly exercise, are increasingly recognized for mitigating therapy-related toxicities. Aerobic and resistance training demonstrate efficacy in reducing symptoms, yet their high-intensity protocols often exclude patients with functional limitations or comorbidities [8], [9], [10], [11]. In contrast, Baduanjin exercise – a traditional Chinese mind-body exercise that integrates gentle, rhythmic movements, diaphragmatic breathing, and mindfulness meditation – offers a low-intensity, accessible alternative [12], [13], [14]. Preliminary evidence suggests its potential in alleviating cancer-related fatigue and modulating inflammatory pathways [15], [16], [17], but rigorous evaluation in aromatase inhibitor-treated populations remains lacking. This single-center randomized controlled pilot study focused on verifying intervention feasibility and preliminary efficacy.

Breast cancer patients treated with aromatase inhibitors frequently experience persistent menopausal-like symptoms (e.g., fatigue, hot flashes, arthralgia), which reduce treatment adherence and impair quality of life (QOL). For QOL assessment in this population, existing studies using standardized questionnaires have confirmed a significant burden: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) shows patients have notably lower scores in physical function, emotional function, and global QOL, with physical discomfort scores negatively correlated with treatment adherence [18], [19], [20]; the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) (designed for endocrine therapy populations) accurately captures the interference of aromatase inhibitor – specific symptoms (e.g., joint pain, hot flashes) on QOL, where the magnitude of score reduction is directly associated with symptom severity [21], [22], [23]; the Breast Cancer-Specific Module 23 (BR23) reveals disease-specific concerns (e.g., body image distress, fear of recurrence) further exacerbate QOL impairment [24], [25], [26]. Thus, based on the existing evidence, we suggest that future exercise intervention studies for this group consider including these three questionnaires pre- and post-intervention to allow for a comprehensive evaluation of QOL improvements. While exercise interventions are increasingly recommended to manage therapy-related side effects, evidence shows that regular physical activity across various forms effectively alleviates menopause-associated symptoms [27], 28]. Existing protocols, however, primarily focus on aerobic or resistance training, which may not adequately accommodate the functional limitations common in this population. The aim of this randomized controlled pilot study was to first verify the feasibility of a 12-week supervised Baduanjin program in this cohort, and second, to explore its preliminary efficacy in alleviating menopausal-like symptoms (assessed via the Kupperman Index and Piper Fatigue Scale) and modulating serum inflammatory biomarkers among patients treated with aromatase inhibitors. The summary of this article is presented in Figure 1. By integrating culturally rooted, low-intensity exercise with objective biomarker analysis, this study sought to address critical gaps in current supportive care strategies, particularly how mind-body exercises distinct from conventional aerobic or resistance training may regulate inflammation to improve symptom outcomes [29], 30]. Such insights could inform tailored interventions to enhance therapeutic adherence and survivorship experiences in breast cancer patients treated with aromatase inhibitors.

Figure 1:

Graphical representation of this study. Key points: (1) breast cancer patients on aromatase inhibitors often experience menopausal symptoms (e.g., arthralgia) and cancer-related fatigue, which hinder treatment adherence, while culturally tailored mind-body interventions like Baduanjin are under-researched for these issues. (2) a randomized pilot study enrolled 39 breast cancer patients on aromatase inhibitors, with 24 in a 12-week supervised Baduanjin exercise group and 15 in control group, assessing symptoms via the Kupperman index/piper fatigue scale and serum inflammatory markers. (3) the Baduanjin group showed reduced arthralgia severity, improved fatigue dimensions, and altered serum inflammatory markers, supporting its feasibility as a culture-specific intervention with further investigation needed on inflammation-symptom links. Figure created with BioRender.

Materials and methods

Results

Subject baseline characteristics

The participants flow through all stages of the study is comprehensively depicted in Figure 2. Of the 70 participants initially enrolled and randomized, a total of 39 individuals (55.7 %) successfully completed the full 12 – week intervention protocol. The attrition rate was 31.4 % (11 out of 35 participants) in the Baduanjin exercise group and 57.1 % (20 out of 35 participants) in the control group. Statistical analysis revealed no significant difference in attrition rates between the two groups. For the control group, which began with 35 randomized participants, 9 participants were lost to follow-up due to a lack of sustained interest in the study procedures. Additionally, 11 participants chose to discontinue the intervention prematurely. As a result, 15 participants in the control group completed all aspects of the study. In the Baduanjin exercise group, starting with an equal initial cohort of 35 randomized participants, 3 participants were lost to follow-up because of diminished interest, and 8 participants discontinued the intervention. Ultimately, 24 participants in the Baduanjin group fulfilled the entire study protocol. Demographic and clinical characteristics of the included patients at baseline are presented in Table 1, revealing no statistically significant intergroup differences in baseline parameters including age distribution, marital status, employment status, disease duration (range: 0.5–8 years post-diagnosis), duration of aromatase inhibitor therapy, or tumor staging classification.

Figure 2:

Flow diagram showing participant enrollment and grouping.

The figure depicts the participant flow throughout the study. Initially, 82 individuals were enrolled and screened for eligibility. Among them, 10 were excluded: 2 had prior Baduanjin training experience, 5 declined participation, and 3 met cancer-related exclusion criteria. The remaining 72 participants underwent pre-intervention evaluation, with 2 further excluded (1 due to ineligibility per medical records, 1 with mobility/functional limitations). A total of 70 participants were then randomized: 35 to the control group (maintaining their usual lifestyle without Baduanjin intervention) and 35 to the Baduanjin group (receiving the allocated intervention). During follow-up, 9 control participants were lost to follow-up (due to disinterest) and 11 discontinued the intervention; in the Baduanjin group, 3 were lost to follow-up (disinterest) and 8 discontinued the intervention. Finally, 15 participants from the control group and 24 from the Baduanjin group were included in the analysis.

Discussion

Contemporary advancements in oncological diagnostics and therapeutics have significantly enhanced prognostic outcomes for breast cancer [35]. However, treatment-induced complications – particularly among patients undergoing aromatase inhibitor therapy – persistently compromise quality-adjusted life years through menopausal symptom burden and cancer-related fatigue [36], 37]. This randomized controlled pilot study provides novel evidence that a 12-week Baduanjin exercise intervention protocol effectively attenuates menopausal symptomatology (particularly arthralgia severity) and mitigates multidimensional fatigue parameters in this clinical population. Mechanistically, the observed IL-6 modulation suggests potential anti-inflammatory pathways underlying these therapeutic effects, though further investigation is required to elucidate precise biological mechanisms.

Baduanjin exercise, a multimodal mind-body practice rooted in traditional Chinese medicine, combines physical postures with cognitive engagement and regulated breathing techniques, demonstrating therapeutic benefits for chronic conditions in female breast cancer patients [38]. This low-complexity intervention, comprising eight biomechanically optimized movements derived from historical wellness traditions, exhibits high accessibility across diverse demographics [17]. The efficacy of Baduanjin for improving psychosocial well-being in breast cancer patients is supported by accumulating evidence from systematic reviews and meta-analyses. These analyses have consistently confirmed its benefits in enhancing health-related quality of life and alleviating depressive symptoms [12], [13], [14, 32], 39]. The present findings provide supportive evidence regarding the potential of Baduanjin exercise in ameliorating vasomotor disturbances, with particular reference to reductions in hot flash frequency observed in aromatase inhibitor-treated patient cohorts [40]. These outcomes appear congruent with established clinical recommendations advocating mind-body interventions as therapeutic strategies for addressing treatment-induced menopausal symptoms [41]. Notably, we observed clinically meaningful reductions in arthralgia severity – a prevalent complication affecting distal joints that frequently compromises treatment adherence [42]. While previous meta-analyses report limited analgesic effects of Baduanjin exercise [13], our results suggest outcome variability may stem from differences in pain etiology (e.g., postoperative vs. treatment-induced), intervention protocols, and population-specific adaptations, underscoring the need for phenotype-stratified investigations.

Breast cancer survivors undergoing aromatase inhibitor therapy frequently report elevated fatigue severity concomitant with menopausal symptomatology. The fundamental mechanism behind fatigue is often linked to inflammation, a response typically triggered by standard cancer therapies, including chemotherapy, or by the cancer itself [43]. Our findings demonstrate Baduanjin exercise’s efficacy in attenuating multidimensional fatigue manifestations, particularly affective and cognitive/mood dimensions, corroborating existing evidence of its therapeutic potential against cancer-related fatigue [39]. Contemporary randomized controlled trial data substantiate these anti-fatigue effects across heterogeneous patient populations, though reduced effect consistency is noted in cohorts aged over 55 years [15]. Mechanistic investigations implicate aromatase inhibitors as potential contributors to fatigue pathophysiology through inflammatory pathways [44], 45], with circulating biomarkers like IL-6 exhibiting dual regulatory properties in inflammatory cascades [46]. IL-6 exhibits context-dependent dual roles in cancer, acting as either a suppressor or promoter of tumor development. During exercise, IL-6 is primarily released from skeletal muscles, whereas in inflammatory foci or the tumor microenvironment, it is secreted by leukocytes and stromal cells. Muscle-derived IL-6 exerts protective effects by enhancing insulin sensitivity in glycogen-storing tissues, stimulating anti-inflammatory cytokine production, mobilizing cytotoxic immune cells, and reducing DNA damage in cancer cells – biological actions that may inhibit cancer initiation and progression. Conversely, sustained IL-6 signaling within inflamed or tumor microenvironments drives chronic low-grade inflammation and activates pro-tumorigenic pathways, thereby promoting cancer advancement [29]. Additionally, IL-6 has been implicated as a critical mediator of pathological pain, including bone cancer pain, through mechanisms such as nociceptor sensitization and amplification of inflammatory signaling cascades [47].

Discrepancies between our findings and other Baduanjin studies likely stem from population-specific differences. For example, middle-aged women demonstrated reduced IL-6 after 12-week Baduanjin, likely reflecting systemic anti-inflammatory effects in metabolically intact populations [48]. Post-stroke patients with depression similarly exhibited decreased IL-6 following combined Baduanjin and psychotherapy, potentially via neuroendocrine-immune regulation of stress-driven inflammation [49]. Conversely, cognitively frail older adults showed non-significant IL-6 changes post-24-week Baduanjin practice, possibly due to age-related immunosenescence or baseline inflammatory lability [50]. Our cohort’s distinct characteristics – breast cancer survivors receiving aromatase inhibitors – introduce critical variables: these agents may disrupt muscle metabolic equilibrium, potentially augmenting myokine IL-6 secretion during rhythmic motor activity [42], 51]. This muscle-derived IL-6 could represent a transient adaptive response promoting glucose homeostasis and anti-inflammatory cytokine synthesis [29], distinguishable from pathogenic IL-6 signaling within tumor microenvironments. The observed elevation might therefore indicate beneficial “metabolic-inflammatory” uncoupling, wherein exercise-induced myokines mitigate therapy-related metabolic disturbances without potentiating pro-tumorigenic cascades. Notably, our observed IL-6 elevation post-Baduanjin exercise contrasts with conventional exercise-induced anti-inflammatory responses [30], suggesting modality-specific immunomodulatory mechanisms requiring further elucidation.

This study provides novel insights into Baduanjin exercise’s therapeutic effects on aromatase inhibitor-associated menopausal symptoms in breast cancer patients, while acknowledging methodological constraints. A key limitation is the small completed sample size (total n=39), which limits the feasibility of sensitivity analyses; multiple imputation or subgroup analyses in such small samples may introduce bias, so additional sensitivity tests were not performed [52]. This underscores the necessity for future studies with expanded sample sizes to verify the robustness of the findings. Other limitations include the notable attrition discrepancy (57.1 % in the control group vs. 31.4 % in the Baduanjin exercise group, p=0.03) – likely due to the lack of structured supervision in the control group – potentially biasing results toward participants with milder symptoms or higher adherence in the control cohort. From a patient management perspective, these findings highlight the importance of personalized support to enhance adherence: clinicians should proactively identify patients at risk of attrition (e.g., those showing early signs of disinterest or perceived burden), use regular follow-ups and tailored motivational counseling to improve retention, and integrate peer-support systems (where experienced participants share their journeys) to boost patients’ confidence and commitment to interventions like Baduanjin. Additionally, the heterogeneous age range (36–70 years), absence of neurocognitive assessments, and 12-week intervention duration (insufficient to address chronic inflammation from prolonged aromatase inhibitor use) further restrict the generalizability of conclusions. In summary, this pilot study suggests that Baduanjin exercise may serve as a feasible, low-intensity adjunctive therapy for ameliorating aromatase inhibitor-induced menopausal symptoms and fatigue, with distinct immunomodulatory effects on IL-6. Further research with larger samples, extended interventions, comprehensive mechanistic assessments (including exploration of IL-6’s dual roles), and refined methodologies (e.g., standardized retention strategies and age-stratified analyses) is needed to validate these findings and clarify the underlying mechanisms.

Conclusions

This pilot study provides preliminary evidence that 12-week Baduanjin exercise may alleviate specific aromatase inhibitor-induced menopausal symptoms (notably arthralgia) and reduce multidimensional fatigue in breast cancer patients, with concurrent modulation of inflammatory markers such as IL-6, tentatively supporting its potential as a low-intensity complementary intervention for managing treatment-related complications; however, due to limitations including a small sample size (n=39), notable attrition bias, and short intervention duration, these findings should be interpreted cautiously, and further well-powered trials with larger cohorts, extended follow-up, and mechanistic assessments – particularly regarding IL-6’s context-dependent role – are needed to validate its therapeutic value.