The impact of exercise prehabilitation on upper extremity range of motions, functionality and quality of life in breast cancer survivors: a prospective clinical trial.

Background
The worldwide estimates of cancer incidence and mortality rates indicate the majority of breast cancer (BC) incidence in females and the lung cancer in males, followed by prostate cancer [1]. Achievement of early diagnosis and treatment increased survival rates however this condition gives rise to long-term complications. With the success of curative applications, need for postoperative rehabilitation becomes essential. After BC treatment both with surgical and radiation therapy (RT) modalities, restriction of shoulder joint, remaining pain syndromes and lymphedema are the common complications along with loss of self-esteem, depression, fatigue and decreased quality of life (QoL). Clinical trials conducted on cancer rehabilitation across various diagnoses demonstrated the effectiveness of exercise therapies on fastening short term recovery, improvement of physical capacity and QoL. In case of BC rehabilitation special attention must be given to upper extremity functions. The aim of this study is to initiate exercise education prior to the surgical and RT procedures that is called physical prehabilitation, and to evaluate its long-term effects on shoulder range of motion (ROM), functional capacity and overall QoL even up to twelve months after surgery [2–4].

Methods

Ethical statement
Ethical approval for this prospective trial was obtained from Local Ethics Committee for Clinical Trials of the Provincial Health Directorate (Decision No:2024-10-61). Written informed consent had been obtained from the patients confirming their agreement in physical examination, treatment, follow-up assessments, data sharing and publication of study results. Helsinki Declaration rules were carried out by the clinicians and all methods were performed in accordance with the relevant guidelines and regulations. Clinical trial registration was retrospectively performed after completion of trial (NCT07240584, 11/16/25).

Participants and data collection
Patients diagnosed with BC and scheduled for surgery, regardless of the surgical procedure type, were referred to a physical medicine and rehabilitation (PMR) specialist. Data including demographical and medical history were collected. Each participant underwent a physical examination at baseline. Patient reported outcome measures (PROM) were also used for evaluation. Home-based exercise programs with specific timelines were prescribed. Patients were followed for 12 months through scheduled visits, including pre-surgery, and at 1, 3, 6, and 12 months post-surgery, during which physical examinations and exercise program reinforcements were conducted (Fig. 1). Patients referred by the surgeon were included in the study. A non-treatment control group could not be established in order to avoid malpractice; therefore, comparisons were made with data from the existing literature.

Physical examination and proms
The physical examination included posture analysis, evaluation of painful movements. Visual analog scale (VAS) was used to understand pain intensity which consists of 10 cm line with two end points, 0 stating no pain whereas 10 for the worst pain had felt. Patients were asked to mark their level of pain on the line which they feel during activities with the upper extremity of cancer side. Assessment of shoulder joint ROM as flexion, abduction, internal rotation and external rotation was performed by using a goniometer. Patients were first asked to move their shoulders as far as they could independently. At the point where active movement ended, passive movement was applied by the physician, and the maximum ROM achieved was recorded. Baseline volume measurements and difference between upper extremity volumes were calculated via truncated cone formula [5]. No radiological imaging was performed during the baseline assessments.
With the purpose of evaluation of functional capacity, fatigue and QoL, the PROMs consisted of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC-QLQ-C30), the Upper Extremity Functional Index-15 (UEFI-15), and the Fatigue Severity Scale (FSS) were performed [6–8]. The EORTC-QLQ-C30 evaluates the impact of cancer and its treatment on patients’ physical, emotional, social, and financial well-being. It comprises twenty-eight questions rated on a four-point Likert scale (from “not at all” to “very much”) and two additional items rated on a seven-point scale assessing overall QoL and general health during the previous week. It is also considered as reliable and valid for the purpose of measuring QoL in cancer patients in Turkiye [6]. The FSS, a validated instrument for assessing fatigue in patients with cancer. The questionnaire represents over the past week, consists of nine items rated on a seven-point scale, with the total score calculated as the average of all responses [7].
Functional evaluation of the upper extremity was conducted using the UEFI-15, which assesses performance in (ADLs) [8].

Exercise intervention
The exercise program was delivered to patients through both visual and written materials, accompanied by face-to-face training sessions conducted by a physiotherapist and physical medicine and rehabilitation specialist. A home-based program was designed separately for the pre-surgery phase, postoperative day 1, day 3, day 7, and the maintenance period. The interviews were conducted face to face, and adherence to the exercise program was monitored. Any deficiencies were identified and the exercises were repeated as necessary. The exercise template included postural correction, diaphragmatic breathing, aerobic, stretching, and resistive strengthening exercises targeting muscles in adjacent to the shoulder joint. Mobilization of scapulothoracic complex via stretching and strengthening exercises of periscapular muscles especially serratus anterior and mid-low fibers of trapezius muscles were tasks. Closed kinetic chain exercises, including push-up, press-up, and pull-up movements, were individually tailored based on the patients’ available equipment (e.g., resistance bands or balls) and could be performed against a wall when applicable. In addition, a remedial exercise protocol commonly used in lymphedema management was incorporated.
Participants were responsible from all movements beginning from the first physiotherapy visit during wait-time up to the surgery. At the early postoperative phase (days 1 and 3), emphasis was placed on diaphragmatic breathing and gentle stretch exercises to maintain ROM. The main program was resumed following the removal of drainage tubes after average 7-days after surgery. During the RT stretching exercises were emphasized again. Exercises were individualized according to days of their surgical and RT processes, pain intensity and restriction of ROM at every visit to the physician.
Patients were advised to perform aerobic exercises including brisk walking of 30 to 60 min, three times per week, while all other exercises were prescribed as daily routines consisting of three sets of ten repetitions for each movement pattern [9, 10].

Outcome measurements
The primary outcome of this study was to evaluate the shoulder joint ROM and functional capacity of upper extremity in BC patients who performed the prescribed regular exercise program prior to surgery and RT. The secondary objective was to investigate the effects of exercise on patients from multiple perspectives using PROMs. Additionally, monitoring the participants’ outcomes across subgroups defined by demographical and medical properties, is expected to contribute to the assessment of determinants influencing treatment outcomes.

Statistical analysis
Statistical analyses were conducted using SPSS version 15.0 (SPSS Inc., Chicago, IL) and JASP version 0.19.1, an open-source software supported by the University of Amsterdam and collaborators. Variable distribution was examined using visual methods (histograms, probability plots) and the Shapiro–Wilk test. Descriptive statistics were reported as means ± standard deviations for normally distributed variables, and as medians with interquartile ranges (IQR) for non-normal or ordinal data.
Because the assumptions for parametric testing were not met, the Friedman test was applied to assess changes in repetitive measures of ROM of shoulder joint across baseline, and the 1st, 3rd, 6th, and 12th months. Subgroup analyses based on demographic and clinical characteristics were performed using the Mann–Whitney U and Kruskal–Wallis tests. A 95% confidence interval was adopted for all analyses. Pairwise comparisons were conducted using Bonferroni adjustment for multiple testing.
Changes in volume difference between extremities, UEFI-15, FSS, and EORTC-QLQ-C30 scores between baseline and twelve months post-surgery were analyzed using the Wilcoxon signed-rank test. Statistical significance was set at p < 0.05.
An a priori power analysis was conducted in G*Power 3.1 for repeated-measures design (α = 0.05, effect size = 0.3). The required sample size to achieve 0.80 statistical power (1 – β) was calculated as thirty participants with a drop-out of 20%.

Results
This prospective prehabilitation trial initiated the exercise program in patients prior to breast surgery and continued it for 12-months postoperatively. The mean duration of the preoperative period was 25-days. Although the target sample size determined by the power analysis was achieved, seven participants discontinued follow-up visits to the PMR outpatient clinics for various reasons. Flow chart of the study design is presented in Fig. 1. Ultimately, the study was completed with 30-women (mean age, 49.93 ± 10.08 years). Demographic and clinical characteristics of the participants are presented in Tables 1 and 2. Before surgery, none of the patients exhibited restriction in shoulder ROM, and only one reported pain during movement.

Treatment modalities varied among patients. From a surgical perspective, modified radical mastectomy (MRM) or breast-conserving surgery (BCS) was performed, while axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB) was applied for lymph node management. Regarding adjuvant therapy, some patients were receiving hormone replacement therapy (HRT). In terms of RT, the chest wall was irradiated in all patients, whereas the axillary and internal mammary lymph nodes were additionally irradiated in a subset of patients. All of the patients undergone planning of intensity modulated RT (IMRT) or volumetric arc therapy (VMAT). Total RT dose was 50 Gy, 25-to-28 fractions in all patients within 2nd month after surgery. None of the patients received postoperative chemotherapy and any of them had acute complication of RT such as dermatitis or brachial plexopathy.
According to Friedman analysis pain scores measured by VAS increased significantly at 1st and 3rd postoperative months compared with baseline. A gradual decline was observed thereafter, continuing through the 12th month (Fig. 2). ROM analyses revealed significant restriction in all directions after surgery up to 1st month. Flexion and abduction levels improved significantly and reached normal levels by 3rd month when compared to 1st month. Whereas the internal rotation normalized significantly at the 6th month and remained stable through the 12th month. The latest recovery was at external rotation with a significant decrease post-surgery 1st month and returning to baseline by the 12th month (Table 3; Fig. 2).

The PROMs demonstrated significant improvements in global health status and QoL item of EORTC-QLQ-C30, as well as in the UEFI-15 and FSS. The evaluation about LE resulted in insignificant inter-limb volume differences (Table 4).

Subgroup analyses examining smoking status, engagement in recreational activity, comorbidities or medication use, involvement of the dominant limb, type of performed lymph nodal dissection (LND), region of applied RT and receipt of HRT revealed no significant impact on ROM values at the end of follow-up.
Comparisons between groups based on age, body mass index (BMI), breast cancer stage, type of surgery indicated significant differences in ROM outcomes at 12 months (Table 5). Functional outcomes, VAS and PROM scores also differed significantly between groups (Table 6). FSS scores were higher among patients with obesity, those not engaging in recreational activity, individuals with stage 2 breast cancer and those who received RT to the the breast or chest wall, including axillary and internal mammary nodal regions. UEFI-15 scores were significantly higher in non-smokers and patients who maintained recreational activity. Pain assessment indicated higher VAS scores among obese patients and smokers through the 12-month follow-up.

Although overall inter-limb volume differences were not significant, the patients with obesity and dominant-limb involvement had higher difference.
Global health and QoL scores were significantly higher in normal weighted and overweight participants than in those with obesity. Patients who undergone BCS and received RT limited to breast or chest wall, without axillary lymph nodes, achieved higher scores in evaluation of QoL.

Discussion
This prospective prehabilitation trial demonstrated that initiating an individualized exercise program before breast surgery and before the onset of adjuvant RT continued for 12 months postoperatively yielded favorable functional and QoL outcomes in women with BC.
The need for rehabilitation following BC treatment is evident, encompassing a broad spectrum of issues such as pain, restricted ROM, neuropathic symptoms, LE, persistent fatigue, depressive syndromes and financial burdens that contribute to physical and psychosocial strain. Persistent pain and shoulder ROM limitation have been reported in up to 50% of BC survivors. These impairments often hinder return to work and performance of ADLs, leading to a substantial decline in QoL [11].
In this trial pain intensity, which increased significantly during the early postoperative period, progressively declined and did not persist by the 12th month. Shoulder ROM improved gradually: flexion and abduction recovered by month 3, internal rotation by month 6, and external rotation by month 12. PROMs including the EORTC-QLQ-C30, UEFI-15 and FSS, showed significant improvements, while inter-limb volume differences were not statistically significant. These findings support the feasibility and effectiveness of a structured prehabilitation in optimizing upper limb recovery and QoL among BC survivors similar to previous trials demonstrating prehabilitation exercises for cancer patients improving functional capacity, patients survival and have been found to be safe and feasible [12, 13].
The early postoperative increase in pain and transient restriction of shoulder mobility align with surgical trauma and soft-tissue tension. After irradiation a cascade of biological events is triggered, including the generation of reactive oxygen species, vascular injury and hypoxia, chronic inflammation, myofibroblast activation, and subsequent fibrosis. The “bystander effect” further contributes to tissue fibrosis, as non-irradiated cells may undergo fibrotic changes due to signaling from adjacent irradiated cells. Unfortunately, these processes may persist for many years after the initial radiation exposure resulting in long-lasting cellular and molecular alterations. Long-term complications, extending up to five years post-treatment, may include adhesive capsulitis, restricted shoulder ROM, and LE [14, 15]. Notably, in our cohort, RT was typically initiated around the second to third postoperative months, coinciding with the period when limited shoulder ROM was still evident. This temporal relationship supports the notion that radiation-induced soft tissue effects contribute to mid-phase functional restrictions. Not used in this trial but objective measurement tools for fibrosis such as elastography may be useful for future research.
According to recent reviews, patients with cancer who undergo RT experience reduced treatment-related morbidity when prehabilitation is implemented. However, most existing studies are limited by small sample sizes and primarily focus on feasibility rather than functional or QoL outcomes. These preliminary findings underscore the need for well-designed trials to evaluate the efficacy of prehabilitation in improving functional status and overall recovery among patients receiving RT [16].
The subsequent reduction in pain is consistent with meta-analytic findings demonstrating that structured exercise interventions can eliminate postoperative pain and stiffness in this population [12]. Early initiation of prehabilitation before surgery and RT likely facilitated tissue adaptation, reduced protective movement behaviors, and promoted long-term recovery, even in the presence of chest wall with axillary and internal mammary lymph nodal RT-induced soft-tissue changes. The timing of RT may have influenced the recovery pattern, but the steady improvements seen in later months suggest that maintaining exercise through RT is safe and effective.
The observed pattern of ROM restoration corresponds with previous reports. Flexion and abduction often recover earlier than rotational movements due to biomechanical and neuromuscular factors, while external rotation tends to normalize last, following ALND or axillary RT [17].
A crucial component in restoring optimal shoulder kinematics is the scapulothoracic complex. Breast surgery and RT frequently alter the dynamic coupling between the scapula and thorax due to pain, soft-tissue fibrosis, and muscle imbalance particularly involving the serratus anterior, lower fibers of trapezius, and rhomboid muscles. Scapular dyskinesis may consequently limit humeral elevation, increase compensatory upper trapezius activity, and perpetuate pain and dysfunction [18]. Scapular stabilization exercises play a central role in the management of scapular dysfunction. The primary aims of these exercises are to achieve selective activation of the scapular stabilizing muscles and to restore normal scapulohumeral rhythm. Exercises targeting activation of the serratus anterior muscle are effective in reducing scapular winging. Closed kinetic chain exercises provide a safe option for enhancing scapular control, particularly during the early and intermediate phases of rehabilitation. Strengthening exercises for the lower and middle trapezius muscles further contribute to improving the scapula’s ability to achieve upward rotation and posterior tilt. During this phase, correct exercise execution and prevention of compensatory movements are of critical importance [19, 20]. Within the current program, early emphasis on scapular mobilization likely facilitated improved scapulohumeral rhythm and pain reduction, while the progressive inclusion of strengthening exercises may have enhanced dynamic stability and functional recovery. As demonstrated in previous clinical studies, restoring scapular mobility and muscle strength prevents shoulder dysfunction, improves posture, and optimizes load distribution across the shoulder girdle during arm elevation [21]. Therefore, integrating targeted scapular stabilization and strengthening into both prehabilitation and postoperative phases is essential to prevent chronic movement compensations and promote long-term functional gains.
Significant improvements in PROMs—including QoL and functional indices—indicate the multidimensional benefits of sustained exercise participation, that prehabilitation and continued rehabilitation improve both physical and psychosocial outcomes in BC populations. The outcome is also considered as benefit of aerobic exercises on improvement of patient well-being, QoL and low fatigue [22–24].
Importantly, the absence of significant limb volume differences supports the growing consensus that exercise does not exacerbate LE risk when appropriately prescribed. This reinforces current clinical guidelines advocating for safe, progressive resistance and aerobic training among BC survivors [17, 25, 26].
Subgroup analyses offered additional clinical insights. Obesity and smoking were associated with higher pain intensity and poorer functional outcomes, findings consistent with prior literature linking these factors to chronic inflammation, impaired wound healing, and reduced exercise tolerance [27, 28]. Conversely, participants who maintained recreational physical activity and abstained from smoking exhibited superior UEFI-15 and QoL scores, highlighting the importance of modifiable behavioral factors in rehabilitation success [29].
Furthermore, patients who underwent BCS and received RT limited to the breast or chest wall demonstrated higher QoL scores, likely reflecting less soft-tissue trauma and preserved musculoskeletal integrity [30].
Comprehensive evaluation of patients at the time of breast cancer diagnosis, particularly regarding risk factors for upper-limb morbidity, and the early initiation of rehabilitation programs can significantly support survivors throughout their recovery journey. Awareness of these risk factors and their influence on morbidity including the type of oncological treatment, surgical procedure, or RT as well as the patient’s habitual behaviors, nutritional status, and emotional well-being, should be interpreted in an integrated and individualized manner to optimize rehabilitation outcomes [11].
In this trial despite the presence of several risk factors significant improvements were observed in PROMs, pain reduction and full recovery of shoulder ROM. These findings demonstrate the long-term benefits of sustained, individualized prehabilitation program extending to 12-months, reinforced by continuous exercise enhancement. In contrast to earlier studies that primarily focused on feasibility, the present trial highlighted measurable gains in both functional recovery and QoL [31].
From a clinical perspective, these findings emphasize the importance of initiating prehabilitation before surgery, RT and maintaining structured rehabilitation during the posttreatment period. Interpretation of PROMs like EORTC-QLQ-C30, FSS and the functional tool UEFI-15 reflected both the adverse impact of BC treatment on functional status and the effectiveness of prehabilitation in recovering these effects.
The novelty of this trial is supporting the recovery of shoulder movements by involving scapular mobilization, strengthening of periscapular muscles combined with stretching specialized according to days of surgery and RT, strengthening of upper extremity muscles along with postural correction, respiratory and aerobic exercises.
Tailoring exercise prescriptions after diagnosis of BC, enhancing physiological reserve and addressing individual characteristics such as BMI, preoperative activity level, and risk factors of adjuvant treatment type may further optimize recovery and minimize chronic impairment risk. The integration of structured prehabilitation into multidisciplinary cancer care pathways should be prioritized to ensure holistic, patient-centered management and improve outcomes across the cancer care continuum [22, 32].

Strengths and limitations
The primary strength of this study lies in its prospective design and 12-months longitudinal follow-up, which allowed for the evaluation of both short- and long-term functional outcomes following breast cancer surgery. The inclusion of a comprehensive, individualized prehabilitation protocol incorporating scapular mobilization, strengthening, aerobic, and respiratory exercises provided a holistic approach that mirrors real-world rehabilitation needs. Furthermore, the concurrent monitoring of objective (ROM) and subjective (PROMs) outcomes offers a multidimensional perspective on recovery.
However, several limitations should be acknowledged. The sample size was relatively small, which may limit the generalizability of the findings. The study was conducted in a single center, potentially introducing institutional bias. Additionally, lack of a control group prevents direct comparison with standard postoperative care. Although adherence was monitored, self-reported compliance may have introduced reporting bias. Finally, variability in RT protocols and surgical procedures could not be fully standardized, which might have influenced shoulder outcomes.
Despite these limitations, the findings provide valuable evidence supporting the feasibility and clinical relevance of long-term, individualized prehabilitation in BC survivors. Future multicenter, randomized controlled trials with larger cohorts are warranted to confirm these results and to refine prehabilitation strategies tailored to treatment phases and individual risk profiles.

Conclusion
This prospective study shows that individualized prehabilitation initiated before breast surgery and continued postoperatively improves shoulder mobility, reduces pain, and enhances QoL without increasing LE risk. In particular, the inclusion of scapulothoracic mobilization and strengthening exercises appear to support the restoration of shoulder mechanics, reinforcing prehabilitation as a safe and effective component of BC rehabilitation. Moreover, the observed associations between obesity, smoking, and poorer functional recovery highlight the need to address modifiable lifestyle factors in future researches.