Introduction

According to the global burden of disease study, breast cancer was the third most prevalent cancer in 2017, with an estimated 2.0 million incident cases (95% Uncertainty Interval (UI), 1.9-2.0 million). In 2019, breast cancer was the most prevalent cause of cancer-related Disability-Adjusted Life Years (DALYs), deaths and Years of Life Lost (YLLs) among females worldwide1. Approximately 90% of Breast Cancer Related Lymphedema (BCRL) cases occur within the first two years after radiation therapy, adjuvant chemotherapy and surgical interventions2.

The diagnosis of lymphedema could be based on a difference of >200 ml in arm volume, >20 mm in arm circumference, or an increase of >10% in volume between the abnormal and normal arms3. The underlying pathophysiology of this condition involves draining interstitial fluid from the skin and subcutaneous tissue by superficial lymphatic capillaries into deeper, larger lymphatic vessels, which then collect and move into axillary lymph nodes. Axillary dissection or lymphangitic infiltration disrupts this mechanism, resulting in lymphedema. The leakage of lymphatic fluid, rich in proteins, into the interstitial space causes eventual fibrosis4. This condition poses significant challenges for breast cancer survivors because they experience multiple symptoms such as swelling, heaviness, limb weakness, reduced quality of life and decreased daily activities5.

The International Society of Lymphology classifies limb lymphedema into four stages and is the most commonly used diagnostic system for BCRL. Stage 0 denotes subclinical or latent limb lymphedema, characterised by no evident volume gain and swelling, but an initially impaired lymphatic network. Stage I, conversely, indicates mild lymphedema, characterised by visible transient limb swelling and volume gain, which may be reduced with limb elevation. Stage II, on the other hand, indicates non-reducible lymphedema, characterised by poor pitting edema and little to no response to limb elevation, serving as an indicator of tissue changes. Finally, stage III denotes overt lymphedema, characterised by tissue changes such as fat and tissue fibrosis, hypertrophic thickened skin, and limb deformities3.

Physical therapy plays a significant role in the treatment, prevention, and early diagnosis of secondary lymphedema6. A previous study by Hemmati et al.7 reported that a combination of complex decongestive therapy, such as manual Lymphatic drainage (MLD), compression therapy with a short stretch bandage, skin care, and lymphedema exercises, along with electrotherapy modalities, results in a more effective course of treatment.

MLD, a specific type of manual therapy, applies delicate strokes in the direction of lymphatic movement, from the proximal to the distal segment, as part of complete decongestive therapy. MLD primarily aims to activate the functioning lymphatic veins and promote lymphokinetic activity. Before compression therapy, MLD is suggested. The treatment is not regarded as a stand-alone one8. An air pump with inflatable auxiliary sleeves or gloves makes up an intermittent pneumatic compression (IPC) system3. They facilitate the body’s lymphatic and venous return from distal to proximal regions8. Similarly, a systematic review by Yao et al. found that both decongestive lymphatic therapy and intermittent pneumatic compression are effective strategies for controlling BCRL. Early implementation of compression therapy is crucial, as it represents a cornerstone in the long-term management of chronic lymphedema. Compression modalities are typically applied during the intensive phase of treatment to reduce swelling9,10.

A systematic review revealed that regular exercise benefits BCRL management by promoting lymph angiogenesis, which may minimise radiation- and dissection-related damage. Exercise raises blood pressure and cardiac output, subsequently increasing capillary filtration and interstitial pressure, thereby facilitating the entry of fluid and proteins into lymphatic capillaries11. Shoulder exercises activate the anterior upper arm muscles (shoulder and elbow flexors) and the posterior upper arm muscles (the deltoid and triceps brachii). Collectively, exercise promotes lymph fluid flow and drainage by increasing muscle tissue pressure while concurrently lowering venous pressure12.

According to the British Lymphology Society, BCRL causes the skin to expand, making it more vulnerable to injury, radiation-induced scarring, and skin infections. Patients with BCRL are educated on maintaining skin integrity and protection through an appropriate skin care regimen, including using low-pH soaps, creams, or lotions at appropriate times and for specific purposes, to prevent skin breakdown and bacterial colonisation13.

Although numerous treatment options exist for BCRL, there is still no consensus on the most effective approach, highlighting the need for further studies exploring comprehensive therapy methods. A previous systematic review suggested effective lymphedema management may involve combined physical therapy11. Therefore, we investigated the effect of a multimodal physical therapy approach in reducing UL lymphedema and increasing the shoulder range of motion (ROM) among women with BCRL.

Methods

Subjects and study design

This study was conducted in accordance with the Declaration of Helsinki, ensuring the ethical treatment of all participants involved. The institutional human ethics committee at the PSG Institute of Medical Sciences and Research granted ethical clearance for the study (Project number: 23/148) (PSG/IHEC/2023/Appr/Exp/173). Institutional Review Board granted a waiver of consent as all data were anonymized and posed minimal risk of subjects.

A retrospective pre-post study was conducted using the data collected from women with BCRL treated at the oncology outpatient department of a tertiary care multispecialty hospital from April 2021 to March 2022. They underwent screening by an oncologist, who referred them to physical therapy. A senior physiotherapist with a master’s degree in Physical therapy and three years of experience in the oncology department treated them.

We obtained data based on the following criteria: Women aged above 18 who underwent tumor resection and at least two levels of axillary lymph node dissection with more than a 2 cm circumference difference between the two upper limbs (unilateral lymphedema stage 0–2) and had completed chemotherapy and radiotherapy were included in this study. Women with any history of neurological or musculoskeletal diseases or deformities in the ipsilateral UL affecting mobility, skin infection, current limb ischemia, venous thrombosis, edema due to impaired heart, kidney, and liver function, and current metastasis were excluded. The collected data at baseline assessment (commencement of the intervention) and at the end of the four weeks (end of Phase I) were used for statistical analysis.

Sample size calculation

G*Power version 3.1.9.7 was used to determine the sample size. A paired t-test with an effect size of 0.8, an alpha error probability of 0.05, and a power (1-beta error probability) of 0.95 requires a minimum of 19 subjects.

Intervention

To ensure complete reporting of interventions, we used a template for intervention description and replication (TIDieR) checklist14 (Table 1).

Table 1 Template for intervention description and replication (TIDieR) checklist.
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Outcome measures

The therapist measured the following variables at baseline and at the end of four weeks of intervention.

Upper limb circumference measurement

The circumference of the UL was measured using an inch tape measure at intervals of 4 cm up the arm from the ulnar styloid to the axilla (0 to 40 cm) and 4 and 8 cm below the hand from the ulnar styloid process. The sum of the circumferences in cm at each level was calculated for both limbs, and the difference between the limbs was taken for final analysis. Researchers have reported excellent intra- and inter-rater reliability when assessing lymphedema with a tape measure, with intraclass correlation coefficient scores ranging from 0.98 to 0.9815.

Shoulder range of motion

Shoulder flexion, extension, abduction, internal rotation, and external rotation in degrees were measured using a universal goniometer. Researchers have reported excellent test-retest reliability (ICC: 0.95 to 0.98) for assessing ROM using a goniometer16.

Statistical analysis

Descriptive statistics were computed for participant demographics. Paired t-tests were conducted to determine the significance of changes in UL circumference and shoulder ROM before and after the intervention. Cohen’s d was estimated for the effect of multimodal physical therapy on breast cancer-related lymphedema, categorising the effect as trivial (< 0.2), small (0.2–0.5), medium (0.5–0.8), or high (> 0.8). All statistical analyses were conducted using SPSS version 16.0 (SPSS Inc., IBM, Chicago, IL), with the risk of type I error set at P < 0.05.

Results

Table 2 provides an overview of the participants’ demographic characteristics. Of the 19 women diagnosed with BCRL, 18 had received radiation therapy. All of them had their lymph nodes dissected at level 3. The participants ranged in age from 44 to 74 years (mean ± SD, 59.57 ± 10.39 years). Most of the participants had stage 2A lymphedema. The mean height and weight of the participants were 151.6 ± 4.67 cm and 60.63 ± 8.63 kg, respectively, with a mean BMI of 26.36 ± 3.58 kg/m2.

Table 2 Demographic characteristics (n = 19).
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Table 3 compares the outcomes from the baseline to the end of the four-week period. The intervention program significantly improved UL circumference and shoulder ROM (p < 0.05). Following the multimodal intervention, UL circumference was significantly reduced by 2.18 cm (95% CI: 1.54 cm, 2.68 cm; Cohen’s d = 1.35; p < 0.05), shoulder flexion increased by 46.31° (95% CI: -57.5°, -35.1°; Cohen’s d = 1.68; p < 0.05), shoulder extension increased by 10° (95% CI: -13.4°, -6.59°; Cohen’s d = 1.74; p < 0.05), shoulder abduction increased by 47.36° (95% CI: -60.35°, -34.38°; Cohen’s d = 1.67; p < 0.05), shoulder internal rotation increased by 18.94° (95% CI: -24.4°, -13.4°; Cohen’s d = 1.37; p < 0.05), and shoulder external rotation increased by 16.05° (95% CI: -20.03°, -12.07°; Cohen’s d = 1.51; p < 0.05).

Table 3 Comparison of outcomes before and after intervention among women with BCRL.
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Supplementary Table 1 presents the subgroup analysis of upper limb circumference and shoulder ROM across women with different lymphedema stages. These analyses demonstrated a progressive reduction in arm circumference and improvement in shoulder ROM after the intervention, with similar improvements observed irrespective of the lymphedema stage.

Discussion

This study aimed to reduce edema by decreasing interstitial fluid accumulation and improving lymphatic function through multimodal physical therapy. The literature has reported mixed results from various initiatives and treatment strategies proposed to address BCRL.

The current study found that women with BCRL had a significant reduction in their affected arm circumference (p < 0.05) with a larger effect size (Cohen’s d = 1.35). Furthermore, Wang et al. discovered that the overall length of the arm circumference in the experimental group was less than that in the control group (126.39 cm vs. 145.26 cm), owing to the experimental group’s participation in UL strengthening exercises and massage. They also said that restoring UL function necessitates lowering edema in the impacted limb, which then improves shoulder function.

Similarly, Borman et al.17 conducted a study and found better improvements in the measurements of lymphedema (p < 0.05) after 3 weeks of a combined protocol of complex decongestive therapy. This included skin care, manual lymphatic drainage, short-stretch multilayer bandaging, and lymphedema exercises17. Moreover, Diab et al.18 evaluated 30 women with BCRL and compared an intervention group that received IPC with Kinesio tape as an addition to complex decongestive therapy to a control group that underwent only complex decongestive therapy. Compared to the control group, the intervention group exhibited a substantial decrease in lymphedema size and a noticeable increase in shoulder ROM18.

Conversely, Blom et al.9 stated that while compression garments combined with self-care initially produced a significant reduction in lymphedema relative volume at 6 months (p = 0.004) compared with self-care alone, this benefit was not sustained at 9 and 12 months. The compression garment group showed a 3.8% decrease in lymphedema volume after 6 months, while the non-compression garment group showed only a 0.1% increase (p < 0.001). Groups were similar at 9 and 12 months9. These findings suggest that the effectiveness of compression garments may be limited to short-term management, highlighting the need for ongoing or adjunctive interventions to maintain long-term benefits9.

In terms of improvements in shoulder ROM, flexion (46.31 ± 23.20; P < 0.001) and abduction (47.36 ± 26.94; P < 0.001) outperformed extension (10 ± 7.07; P < 0.001) in the current study. These improvements reached the minimal detectable change (MDC) set by Rasmussen et al.19 at 20.80 and 10.20 for abduction and flexion, respectively. Consistent with our findings, a previous review by Stuiver et al.20 found that early shoulder exercises and MLD improved shoulder mobility for abduction and forward flexion in the initial weeks following breast cancer surgery. Early shoulder exercise improved forward flexion at one- and six-month follow-up, but not at 12 months20. On contrast, a previous study by Otero et al. on 43 women with lymphedema found that IPC and complex physical therapy for first three weeks worked better together to improve shoulder flexion (5.6 ± 20.0; P = 0.04), extension (5.0 ± 9.5; P = 0.001), and abduction (11.4 ± 30.7; P = 0.024)21, but they did not meet the MDC set by Rasmussen et al.19. Instead, Basha et al.22 determined the effects of virtual reality and resistance exercise training on BCRL over eight weeks and found mean between-group differences of 13.00, 21.170, and 8.930 for shoulder flexion, abduction, and external rotation. When compared to Rasmussen et al.19, MDC values of 10.20 for flexion and 20.80 for abduction, the study by Basha et al.22 showed improvements in flexion and abduction exceeded the MDC thresholds, indicating true functional changes beyond measurement error. The observed shift in external rotation did not exceed the MDC set by Rasmussen et al.19, suggesting that clinically relevant improvements in this movement may not be possible. Similarly, Cho et al.23 examined the effects of physical therapy combined with MLD for four weeks on shoulder function in 41 women with axillary web syndrome. They found that both groups significantly improved shoulder flexion and abduction, with both groups achieving a full range of motion (180°) and satisfying MDC requirements set by Rasmussen et al.22,23.

In our study, improvements in internal rotation (18.94 ± 11.49; p = 0.000) exceeded those of external rotation (16.05 ± 8.26; p = 0.000) and had a larger effect size. However, Rasmussen et al.19 specified that MDC values were only met for internal rotation (9.2) but not for external rotation (20.1) of the shoulder. Similarly, Luz et al. found that complex physical therapy (which includes regular exercises, skin care, manual lymphatic drainage, and multilayer bandage compression therapy) improved shoulder internal rotation (17.6 ± 32.6; p = 0.03) more than complex physical therapy combined with strength training.

Limitations, methodological considerations, and future recommendations are acknowledged. The retrospective pre–post design without a control group precludes causal inference, as observed improvements may partly reflect natural recovery, or concomitant therapies received outside the knowledge of the treating therapist. Furthermore, regression to the mean must be considered; patients exhibiting more severe lymphedema at baseline assessment may have experienced natural improvement over time, regardless of the multimodal intervention. Therefore, our results require careful interpretation, and future randomised or controlled clinical trials are required to validate these results.

The limited sample size (n = 19) constrains statistical power, increases susceptibility to individual variability, and raises the likelihood of Type II error. To address this, a sensitivity analysis was carried out using G*Power version 3.1.9.7 to determine the Minimum Detectable Effect (MDE) at 80% power and 5% significance. The MDE values (− 0.54 cm for limb circumference, − 3.20° for flexion, 1.31° for extension, − 2.54° for abduction, 2.55° for internal rotation, and 1.56° for external rotation of the shoulder) suggest the study was adequately sensitive to detect clinically meaningful changes, as evident in Table 3, despite the small sample size. Even so, outcomes were only evaluated at baseline and four weeks, which prevented the assessment of long-term retention of effects. Future research with extended follow-up is needed to ascertain the durability of outcomes. The onset of lymphedema varied across participants, who were women aged 40 to 75 years and had undergone various types of breast surgery.

External validity is limited by the single-centre, retrospective design and the relatively brief follow-up period; however, internal validity remains sound due to the utilisation of objective assessment methods and standardised therapeutic protocols. The results are still clinically relevant for Indian women with BCRL, where limited resources and different levels of access to specialised rehabilitation services make pragmatic, multimodal physical therapy approaches even more important.

Finally, limb circumference was measured using a tape measure, a reliable method in the literature, reducing the possibility of bias. Nonetheless, measurements were carried out without blinding or duplicate evaluation, which may have resulted in measurement error. Patient-reported outcomes, such as overall quality of life and symptom load, were not measured, preventing a thorough assessment of the intervention’s effectiveness. Future studies should therefore incorporate validated patient-reported measures alongside objective assessment.

Conclusion

The study findings indicate that our multimodal physical therapy approach effectively reduces excess arm volume and enhances shoulder ROM in BCRL, supporting its potential use in clinical practice for lymphedema management. However, randomised or controlled clinical trials are further required to confirm these findings.