Introduction

Breast cancer is the most common type of cancer and the most frequent cause of mortality among women all over the world [1]. While a significant decrease has been witnessed in mortality rates thanks to the developments seen in breast cancer diagnosis and treatment alongside an increase in social awareness, significant increases were also observed in functional insufficiency and disability rates pertaining to the disease and the treatments applied [2].

Breast cancer may lead to various functional losses due to the nature of the disease itself, radical surgical interventions, and radiotherapy. Psychological and cosmetic problems can be listed among these, alongside shoulder dysfunction (pain and joint movement limitation), loss of upper extremity muscular strength, and lymphedema (LE); consequently, these problems affect patients’ quality of life (QOL) [3, 4]. LE after breast cancer therapy has been reported at various rates ranging between 4 and 30%. The risk factors in LE development include radiotherapy, wide axillary dissection, obesity, and recurrent cancer presence in axillary lymph nodes [5, 6].

LE is a chronic, life-long process. There is only a limited number of studies in our country which have investigated QOL and factors affecting it in patients who contracted LE after having surgical procedures because of breast cancer [7]. Thus, the aim of this study was to evaluate QOL in female patients who had developed LE following unilateral breast cancer surgery and to investigate its relationship to shoulder pain, disability, sleep and depression.

Materials and methods

Patients

A total of 69 female patients aged between 30 and 80 years with LE after unilateral breast cancer surgery who had presented to Konya Training and Research Hospital’s Physical Medicine and Rehabilitation outpatient clinic to pursue treatment and follow-up, and 69 healthy women of the same age group making up the control group who had not been diagnosed with breast cancer were included in the study.

Patients with bilateral breast cancer, those with previous history of neuromuscular or musculoskeletal disorders affecting upper extremity functions, those with major psychiatric disorders, and those with lymphangitis were excluded from the study. Exclusion criteria for the control group were ascertained to be previous history of neuromuscular or musculoskeletal disorders affecting upper extremity functions and major psychiatric disorders.

The participants were informed about the fact that they were included in the study. The study was designed as a cross-sectional one and conducted in accordance with the Declaration of Helsinki. Written consent was obtained from the patients, demonstrating that they voluntarily participated in the study.

The patients clinical and sociodemographic information, therapies received because of breast cancer, duration of LE, and therapies received because of LE were recorded.

Assessments

Within the framework of LE assessment, both arms were measured beginning with the wrist in 4 cm intervals up to 40 cm using Kuhnke’s disk model [8]. Circumferential difference of more than 2 cm at any point in comparison to the healthy side was regarded to be LE. Moreover, the circumferential measurements of both arms in the patient group were converted into volumes through the Frustum formula [9]. LE classification was carried out by the staging method. Stage 1 LE is classified as reversible LE. At this stage the patient has a soft and pitting edema with no fibrosclerotic tissue alterations. Stage 2 LE is irreversible LE and can be pitting. Fibrosclerotic tissue alteration is accompanied by tissue proliferation. Stage 3 LE is classified as elephantiasis. At this stage, the severity of tissue alterations such as tissue volume, fibrotic response and papilloma, fistula, and hyperkeratosis increase significantly [10].

The participants’ QOL was evaluated by the Short Form-36 (SF-36), while their depression levels were determined by the Beck Depression Inventory (BDI), their functional statuses were investigated by the Short Form-Disabilities of the Arm, Shoulder, and Hand Questionnaire (Q-DASH), and their quality of sleep was evaluated by the Pittsburgh Sleep Quality Index (PSQI). The patient group’s QOL was assessed by the Turkish version of the EORTC-QLQ C‑30 quality of life questionnaire developed by the European Organization for the Research and Treatment of Cancer (EORTC). Shoulder pain on the operated side in the patient group was appraised by the visual analogue scale (VAS). For the appraisal, a 10 cm line was drawn and numbered at one-cm intervals. The patients were informed about the fact that 0 = painless while 10 = most severe pain, and they were asked to mark the value equivalent to their pain on the scale. VAS ≥ 1 was defined as pain. Passive shoulder joint range of motion (ROM) was measured by goniometer in the patient group.

SF-36 is the most commonly used QOL survey in the medical field and includes a total of 36 items evaluating physical and mental health. It is comprised of two summary scales and eight subscales. The physical component summary scale is composed of physical functioning, physical role limitation, bodily pain, and general health perception subscales, while the mental component summary scale is formed by vitality, social role functioning, emotional role functioning, and mental health subscales. Higher scores indicate better health status. The survey was adapted for the Turkish society [11, 12].

EORTC QLQ C‑30 version 3.0 is a multidimensional questionnaire which assesses global health status and QOL through five functional scales and three symptom scales with 30 questions. The functional scales consist of physical, role, cognitive, emotional, and social functioning items. Symptom scales, on the other hand, evaluate fatigue, pain, and nausea/vomiting. Moreover dyspnea, insomnia, loss of appetite, constipation, diarrhea, and financial dire straits are measured by one question for each item. Each parameter has a score between 0 and 100. While the highest score on the functional scale refers to good health status, a high score on the symptom scale represents a high level of symptomatic problems [13].

The BDI is a valid and reliable method to measure depressive symptoms in a society. It is made up of 21 items pertaining to depressive symptoms. Within the framework of our study, BDI ≥ 17 will be interpreted to indicate depression. BDI’s validity and reliability study for Turkish persons has been conducted [14].

The PSQI was developed by Buysse et al. and adapted to Turkish by Ağargun et al. [15, 16]. PSQI is composed of seven components that assess sleep quality and disorders over a one-month time interval. While 19 questions are self-rated, 5 questions are rated by the bed partner or the roommate. Each question is rated over 0–3 points. The total score obtained from seven components indicates the total scale score. The total score ranges from 0 to 21. A total score greater than 5 represents “poor sleep quality.”

QUICK-DASH is a region-specific questionnaire which was developed for upper extremity musculoskeletal disorders and consists of 11 questions. In order to calculate QUICK-DASH scores, at least 10 of the 11 items must be answered. Each question is scored one a five-point scale and a final score varying between 0 (no disability) and 100 (most severe disability) is calculated. The questionnaire was evaluated to be valid and reliable in Turkish as well [17].

Statistical analysis

The statistical analyses in the study were conducted by the SPSS 21.0 software program (IBM Corp., Armonk, NY, USA). Descriptive measurements of all variables were calculated. While categorical variables were presented in frequency and percentage rates, numeric variables were offered as (mean ± standard deviation) or (median, min, max) tables. The one-sample Kolmogorov–Smirnov test was used to check whether the numeric variables were in line with a normal distribution or not. Comparative analyses of numeric variables were carried out on the axis of patient/control groups. While Mann–Whitney U test was used for two independent groups, the Kruskal–Wallis variance method was used in cases where there were more than two groups. Monte Carlo simulation of the chi-square analysis method was preferred in order to determine the relationship among categorical variables. Nonparametric Spearman’s rho correlation analyses were performed in order to establish correlations among numeric variables and the p-values related to correlation values were obtained. The volume rate of arms with LE was considered to be a dependent variable and a regression model was created accordingly. The models were formed through enter and forward methods. The adjustment, residuals, and multicollinearity analyses of the model were also carried out. A p < 0.05 value was set as statistically significant throughout the study.

Results

The patient and control groups were similar with regard to age, height, weight, employment status, familial structure, and marital status (p > 0.05). Table 1 summarizes the sociodemographic data.

Table 1 Clinical and sociodemographic characteristics of the lymphedema and control groups
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Mean duration between the date of the surgical procedure that LE patients underwent and the date they were included in our study was 4.28 ± 4.44 years. The mean duration of LE was 2 ± 2.8 years. The time period between surgery and LE development varied between 1 month and 184 months, with a mean duration of 27 ± 40 months. 84.1% of the patients had had modified radical mastectomy (MRM). A large majority of them had received chemotherapy (CT) and adjuvant radiotherapy (RT), while nearly all (94%) had received axillary lymph node dissection (ALND). Table 2 presents the treatments that LE patients had received because of breast cancer, while Table 3 offers their clinical characteristics related to LE.

Table 2 Treatments received by lymphedema patients because of breast cancer
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Table 3 Clinical characteristics of lymphedema patients
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The largest circumferential measurement difference in the patients was 10 cm distal of the lateral epicondyle (3.97 ± 3.22). Moreover, the difference in diameter and the rate of circumferential difference increased as one progressed from the distal to the proximal end of an extremity. 43.5% of the patients had limited shoulder movement towards at least one direction. This limitation was most commonly found in shoulder flexion and abduction. The arm VAS was significantly higher in patients with limitations in range of motion (ROM; p = 0.036), but no significant differences were found in other parameters.

The SF-36 subscale and summary scores in the patient group were significantly lower than those of the control group (p < 0.05). The Q‑DASH score assessing upper extremity functions was significantly higher in the patient group (p < 0.001). The patients’ BDI and PSQI scores were found to be significantly higher than those of the control group (respective p-values: p < 0.001, p = 0.003). 34.8% of the patients had varying degrees of depression and 33.3% had disrupted quality of sleep. These data are summarized in Table 4.

Table 4 The PSQI, BDI, BAI, CIS, SF-36, and Q‑DASH scores of the patient and control groups
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According to Spearman’s correlation analysis, while a positive correlation was ascertained between the rate of difference in volume between two extremities and BMI and age (respective r scores: 0.394, 0.370), a negative correlation was established with the SF-36 physical health summary scale and the EORTC QLQ-C30 physical functioning subscale (respective r scores: 0.257, −0.293).

It was observed that the stage of LE increased as age, BMI, and the duration of LE went up, and the SF-36 physical functioning subscore decreased as the stage of LE increased. Also, Q‑DASH scores negatively correlated with the SF-36 physical functioning subscore (Fig. 1). The parameters with significant differences according to the stages are presented in Table 5.

Fig. 1
figure 1

SF-36 physical functioning subscore and dash total score correlation

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Table 5 Parameters with significant differences according to stages
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Discussion

Patients with breast cancer are at great risk for LE development because of axillary lymph node dissection and radiotherapy. Although LE is not a life-threatening condition, it can bring about infections in the extremity, disability, dysfunction, and pain. Even in cases where there is no pain and swelling, patients may complain about disturbing conditions like sensation of weight. This, in turn, results in problems such as anxiety and depression over time. Consequently, the patient’s QOL is negatively affected by all of these in time [3, 4].

In their study comparing the QOL of patients with a history of breast cancer surgery to healthy controls, Rietman et al. [18] stated that breast cancer patients’ QOL, physical functioning, energy, and general health scores were significantly reduced. Similarly, the results of our study revealed that the mean scores of physical and mental component subgroups, which are SF-36 subscales, were lower than those of the control group. The differences in all subgroups were statistically significant as well. The physical functioning subscore of stage 1 LE patients was found to be significantly higher than those of stage 2 and stage 3 patients. Since LE stage and loss of physical function increase as patient age increases, we think that more sensitivity should be taken to preserve physical function in elderly patients.

Shoulder pain was often reported by patients with breast cancer (between 9 and 68%) [19]. Muscular tension, neurogenic pain, axillary web syndrome, myofascial pain syndrome, adhesive capsulitis, and rotator cuff lesions are listed among the causes of pain in such patients. The fact that a breast cancer patient also has LE further increases the probability that she will develop shoulder pain. A previous study conducted with LE patients ascertained that 71.1% of patients had shoulder pain on the affected side [20]. In parallel with this study, the results of our study revealed that 85.5% of the patients had shoulder pain on the affected side. The VAS values of the patients were found to be 3.75 ± 2.13. Arm VAS was significantly higher in stage 2 and 3 patients in comparison to stage 1 patients. The fact that almost all the patients had had axillary lymph node dissection and a large majority of them had received radiotherapy might have brought about a high prevalence of shoulder pain in our study.

A large majority of studies in the literature found shoulder ROM limitation on the operated side to varying degrees. However, due to differences in surgical techniques, RT fields and dosages, data on upper extremity limitations are quite different. While Selçuk et al. [21] ascertained that 81.3% of the patients had ROM limitations in their study which investigated the cases of 96 patients who had had breast surgery and axillary dissection, Kaya et al. [22] found ROM limitation towards one or more direction on the operated side at a rate of 33.8%. Axillary RT further increases the risk with its fibrosis effect [23]. We, too, found that 43.5% of the patients had limitations in the shoulder towards at least one direction in our study. ROM limitation was most often detected in shoulder flexion and abduction. Arm VAS was significantly higher in patients with ROM limitation, whereas no significant difference was found in other parameters. The results of the Q‑DASH used to assess upper extremity functions revealed that scores were significantly higher in the patient group than the control group—in those with ROM limitation than those without—and in stage 2 and 3 patients than stage 1 patients. Therefore, the development of LE should be prevented by initiating early treatment of the patients and it should be aimed to conserve total ROM by pain control management through ROM exercises in the early postoperative period in order to minimize upper extremity disability.

In a review by Morgan P.A. et al., the authors stated that LE patients suffered from a greater rate of dysfunction, poor psychological balance, anxiety, and depression than the general population [24]. In line with the literature, the results of our study revealed that LE patients had significantly higher BDI scores than those of healthy controls: 34.8% of the patients were diagnosed with depression. LE patients should be followed up for depression during diagnosis and follow-up and they should be referred to appropriate centers for treatment when detected. We believe that the treatment of depression accompanied by LE may render it easier for these patients to be able to cope with the disease.

LE can bring about sleep disorders in patients to varying degrees. Isaksson et al. [25] found in their study that women suffered from pain the most within the first 6 months after LE development and from numbness in the arm and disturbed sleep after a couple of years following LE development. The results of our study revealed that the PSQI values were significantly higher in the patient group than the control group as well. One third of the patients suffered from disturbed sleep quality. Thus, LE patients should be followed up for sleep disorders during diagnosis and follow-up and they should be referred to appropriate centers when such disorders are detected.

Consequently, alongside psychological trauma, musculoskeletal disorders of the operated upper extremity in patients with breast cancer surgery followed by LE development prove to be an important factor which affects the functional life and activities of everyday life of the individual. The fundamental goal in the rehabilitation of such patients should include informing patients about probable upper extremity problems before or immediately after breast surgery, taking protective measures for LE, conducting measurements through regular follow-ups, and protecting patients’ QOL by initiating treatment of LE patients in the early period. It is important for physical medicine and rehabilitation physicians to remember that especially elderly and obese patients, those with a high number of metastatic lymph nodes, and those who received axillary radiotherapy and chemotherapy pose a high risk for LE development when evaluating patients for LE following breast cancer treatment. Physicians should not only focus on upper extremity functions during the diagnosis and follow-up of LE patients but also refer them for psychiatric evaluation, and appropriate treatment should be planned for such patients if they suffer from depression, anxiety, and sleep disorders, while the patients’ QOL should be improved by enabling them to participate in social life and accommodate themselves with the treatment. Although LE is perceived to be an untreatable disease by society, it can indeed be kept under control by early intervention. Therefore, patients should definitely be evaluated by a physiatrist following breast cancer surgery and the detection and treatment of their problems should be ensured.