Predictors of Quality of Life in Patients with Breast Cancer-Related Lymphedema: Effect of Age,Lymphedema Severity,and Anxiety

Abstract

Background:

Patients with breast cancer-related lymphedema (BCRL) have lower quality of life (QOL). However, some important predictors, such as the effect of age, lymphedema severity, depression, and anxiety, have not yet been discovered. The overall objective of this study is to explore the QOL predictors associated with BCRL in China.

Methods and Results:

A cross-sectional design was conducted. Data were collected before treatment, including sociodemographic characteristics (height, heaviness, age, education level, work status, marital status, and economic status), clinical characteristics (surgical method, clinical cancer stage, lymphedema severity, and lymphedema duration), the hospital anxiety (HA) and depression scale, and the functional assessment of cancer therapy-breast quality of life instrument. Univariate analysis or bivariate correlation was first made to explore the correlation of QOL with sociodemographic/clinical characteristics, anxiety, and depression. The multiple linear regression model was used to identify the independent QOL predictors. Seventy-one patients with BCRL were recruited. Age, education level, work status, family income, lymphedema duration, lymphedema severity, and HA and hospital depression scale scores are significantly correlated with QOL (p < 0.05). Age, lymphedema severity, and HA accounted for 85.9% in QOL (F = 62.76, p < 0.001).

Conclusions:

Age, lymphedema, and anxiety are the most important QOL predictors. Therefore, it is very important to establish a BCRL prevention system and pay attention to psychological distress in the patients with BCRL.

Introduction

Breast cancer-related lymphedema (BCRL) is one of the most typical long-term complications after breast cancer surgery and radiotherapy. According to the relevant reports, the incidence rate of BCRL is as high as 65% and, depending on surgical techniques, axillary sampling method, the area of radiotherapy, and the use of chemotherapy, it may possibly be underestimated.^1,2 It occurs as a result of damage to the lymphatic system near the affected breast area, impeding the flow of lymph fluid throughout the affected area, as well as the arms and/or hands. Depending on the severity of damage to the lymphatic system, the accumulation of lymph fluid can cause various symptoms. Common symptoms of lymphedema are swelling, heaviness, tightness, numbness, and pain in arms or hands.^3,4

Quality of life (QOL) is an established prognostic indicator for breast cancer.⁵ It is a multidimensional subjective assessment of physical, psychological, and social health fields, which generally represents the health status of patients.⁶ Many studies show that the patients with BCRL have significantly lower QOL than those without lymphedema.^7–11 Several studies have explored the factors affecting the QOL associated with lymphedema.^12–15 Among them, Tsauo et al.¹⁴ used the ICF model to predict the QOL of patients with BCRL, but it only accounted for 20.5% to 55.6% of the variance in each domain of health-related QOL. As such, some important predictors may not have been discovered.

It is widely reported in previous studies that patients with BCRL have worse mental problem than patients without lymphedema.^16,17 Pain, swelling, numbness, and other uncomfortable symptoms caused by lymphedema may increase the negative emotions of patients with BCRL, such as anxiety and depression. Previous studies show that the higher the anxiety and depression scores of patients with breast cancer, the lower their QOL.^18–20 However, to date, none of the researches on the QOL associated with BCRL has focused on the correlation of QOL with anxiety and depression. The effect of anxiety and depression on the QOL of patients with BCRL remains unclear.

In addition, the effect of lymphedema severity on the QOL of patients with BCRL is still controversial. In Tsauo's ICF model, there was no significant correlation between arm swelling and physical function.¹⁴ It seems that lymphedema severity is not a QOL predictor. Lee et al.'s study shows the similar conclusion.¹³ However, Mak et al.¹² and Giray and Akyuz ¹⁵ believe that patients with severe lymphedema have lower QOL than those with mild lymphedema. Therefore, more evidence is required to determine whether lymphedema severity affects the QOL of patients.

The overall objective of this study is to explore the QOL predictors of BCRL in China. The specific steps of our study are: 1.

Analyze the correlation of QOL with sociodemographic and clinical data, depression, and anxiety in Chinese patients with BCRL.

Determine which of these physical and psychological variables is the most important QOL predictor.

Materials and Methods

Study design

We adopted a cross-sectional design. The study was conducted from January to October 2019. The study protocol was approved by the Ethics Committee of Sun Yat-Sen University Cancer Center.

Subjects

Participants were recruited using the convenient sampling method at Sun Yat-Sen University Cancer Center. The inclusion criteria are: (1) newly diagnosed as secondary lymphedema to breast cancer; (2) aged 18 or over; and (3) adequate literacy skills. The exclusion criteria are: (1) bilateral mastectomy; (2) metastases or other systemic disease (such as cerebrovascular disease, kidney disease, or heart disease); and (3) other life-threatening diseases or serious systemic infections. Written informed consent was obtained from all the participants. The estimated sample size was calculated using the empirical method.²¹ At least 72 patients were required with 12 independent variables in this study, plus a 20% loss rate.

Measures

Sociodemographic and clinical characteristics

Sociodemographic characteristics include height, heaviness, age, education level, work status, marital status, and economic status, while clinical characteristics include surgical method, clinical cancer stage, lymphedema severity, and lymphedema duration. The body mass index (BMI) is calculated by weight (kg)/height × height (m²). Diagnosis and clinical stage of lymphedema were assessed by lymphedema therapists and classified as Stages 0, I, IIa, IIb, and III in accordance with the International Society of Lymphology (ISL) staging system.²²

The ISL clinical stages are shown below. Lymphedema severity is classified as mild (Stage 0–I), moderate (Stage IIa), or severe (Stage IIb–III).¹³

The ISL clinical stage

Stage 0: In the latent or subclinical state, limb swelling is not obvious, but the patients report the feelings associated with swelling, such as heaviness, tightness, and pain.

Stage I: The early accumulation of lymph fluid can be solved by raising the limbs, and the accumulation phenomenon has little or no pitting.

Stage IIa: Visible swelling with significant pitting, and is rarely resolved by raising the limbs.

Stage IIb: Tissue swelling with little or no pitting, and cannot be reduced by raising the limbs alone.

Stage III: Lymphostatic elephantiasis with a large, distorted swelling area and very hard skin and tissues, but without any pitting.

Hospital anxiety and depression scale

Hospital anxiety and depression scale (HADS) was developed in 1983,²³ including two subscales, hospital anxiety (HA) and hospital depression (HD), with a total of 14 items. Each item has a rating from 0 to 3. HA is obtained by summing up seven single items, while HD is obtained by summing up seven double items. The higher the score is, the stronger the anxiety or depression. A score of 0 to 7 points indicates no anxiety or depression. A score of 8 to 10 points indicates mild anxiety or depression. A score of 11 to 14 points indicates moderate anxiety or depression. A score of 15 to 21 points indicates severe anxiety or depression. The Cronbach's for the HADS, HA, and HD subscales is 0.879, 0.806, and 0.806, respectively. In this study, the Cronbach's for HADS is 0.882.

Functional assessment of cancer therapy-breast quality of life instrument

Functional assessment of cancer therapy-breast quality of life instrument (FACT-B) is a widely used QOL questionnaire for patients with breast cancer.⁵ The scores are then calculated by summing up those of five subscales, to provide physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and breast cancer additional concerns subscale (BCC), focusing on the issues which are particularly relevant to patients with breast cancer.⁵ A high score means better QOL. FACT-B has shown acceptable reliability and validity in China.²⁴ The Cronbach's for FACT-B is 0.915 in this study.

Data collection

In this study, data collectors were blind to the results. Sociodemographic characteristics, HADS, and FACT-B were filled out by the patients; clinical characteristics were collected from medical records by the collectors not knowing the study. All data were collected before clinic treatment.

Statistics

Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) for Windows version 20.0 software (IBM Corp., Armonk, NY).

The characteristics of patients were analyzed using descriptive studies. Univariate analysis or bivariate correlation was first carried out to determine the factors affecting QOL. An ANOVA (analysis of variance) test was used to compare the QOL of patients with different sociodemographic and clinical characteristics, such as education, marital status, work status, family income, surgery type, clinical cancer stage, lymphedema duration, and lymphedema severity. Pearson correlation was used to study the correlation of QOL with age and BMI. Spearman correlation was used to study the correlation of QOL with anxiety and depression. Significant predictors were then used as independent variables in the further stepwise multiple regression.

The multiple linear regression model was used to identify the independent QOL predictors. Square of the correlation coefficient (R²) is the coefficient of determination, representing the percentage of the total variance in the scales of dependent variables, and can be explained by the independent variables. A p-value of 0.05 is considered as statistically significant.

Results

Sociodemographic and clinical characteristics, HA score, and HD score

A total of 78 patients with BCRL met the inclusion criteria and provided informed consent. As 7 patients refused to participate in the study, 71 patients finally completed the questionnaire with a loss rate of 8.97%. All the patients were female. The descriptive data on sociodemographic and clinical characteristics, HA score, and HD score are summarized in Table 1.

Table 1.

Correlation of Quality of Life (Functional Assessment of Cancer Therapy-Breast Quality of Life Instrument) with Sociodemographic Characteristics, Clinical Characteristics, Hospital Anxiety, and Hospital Depression (N = 71)

Variables	N (%) and M ± SD	FACT-B score, M ± SD	r/F	p
Age	52.14 ± 9.19		0.35^a	0.006
36–45	18 (25.4)	85.17 ± 19.89
46–55	24 (33.8)	94.21 ± 20.28
56–65	22 (31.0)	100.64 ± 18.54
≥66	7 (9.9)	108.00 ± 15.01
BMI, kg/m²	24.29 ± 3.28		−0.08^a	0.521
≤23.9	34 (47.9)	96.88 ± 19.00
>23.9	37 (52.1)	93.78 ± 21.28
Education			4.94^b	0.013
Middle school or below	29 (40.8)	90.31 ± 20.54
High school/vocational college	16 (22.5)	89.94 ± 22.10
College degree or above	26 (36.6)	104.08 ± 15.58
Marital status			0.45^b	0.505
Married	63 (88.7)	95.84 ± 20.84
Single/divorced/widowed	8 (11.3)	90.75 ± 13.51
Work status			17.21^b	0.035
Full-time	9 (12.7)	84.44 ± 4.80
Part-time	9 (12.7)	103.56 ± 13.37
Retired/unemployed	53 (74.6)	95.27 ± 20.14
Monthly family income			55.60^b	0.007
<RMB5000	33 (46.5)	88.21 ± 22.61
≥RMB5000	38 (53.5)	101.39 ± 15.56
Surgery type			1.28^b	0.289
Mastectomy+ALND	45 (63.4)	15.20 ± 8.13
Mastectomy+SLNB	4 (5.6)	8.25 ± 6.13
Breast-conserving+ALND	19 (26.8)	13.68 ± 3.71
Breast-conserving+SLNB	3 (4.2)	12.67 ± 9.71
Clinical cancer stage			1.78^b	0.176
I	25 (35.2)	95.76 ± 19.62
II	28 (39.4)	99.43 ± 17.64
III	18 (25.4)	88.11 ± 23.39
Lymphedema duration, years			15.83^b	<0.001
<1	24 (33.8)	105.04 ± 9.23
1–5	31 (43.7)	97.87 ± 19.96
>5	16 (22.5)	75.56 ± 19.59
Lymphedema severity			68.33^b	<0.001
Mild	31 (43.7)	109.97 ± 8.60
Moderate	20 (28.2)	96.60 ± 15.47
Severe	20 (28.2)	71.15 ± 13.09
HA	7.06 ± 3.38		−0.42^c	<0.001
No	45 (63.4)	97.31 ± 5.16
Mild	16 (22.5)	93.90 ± 5.17
Moderate/severe	10 (14.1)	76.78 ± 7.47
HD	7.24 ± 4.38		−0.44^c	<0.001
No	47 (66.2)	93.35 ± 6.62
Mild	14 (19.7)	87.14 ± 5.19
Moderate/severe	10 (14.1)	87.50 ± 6.20

Means Pearson correlation with FACT-B.

Means Spearman correlation with FACT-B.

Means comparing the QOL of different characteristics with the ANOVA test.

ALND, axillary lymph node dissection; ANOVA, analysis of variance; BMI, body mass index; FACT-B, functional assessment of cancer therapy-breast quality of life instrument; HA, hospital anxiety; HD, hospital depression; M, mean; QOL, quality of life; SD, standard deviation; SLNB, sentinel lymph node biopsy.

The average age of the 71 patients was 52.14 ± 9.19 years (range = 36–71). Their BMI was 24.29 ± 3.28 kg/m² (range = 15.24–33.30). Thirty-seven percent of the patients were overweight. The HA subscale score was 7.06 ± 3.38, of which 45 (63.4%) patients had no anxiety, 16 (22.5%) patients had mild anxiety, and 10 (14.1%) patients had moderate or severe anxiety. The depression score was 7.24 ± 4.38, of which 47 (66.2%) patients had no depression, 14 (19.7%) patients had mild depression, and 10 (14.1%) patients had moderate or severe depression.

Correlation of QOL (FACT-B) with sociodemographic and clinical characteristics, anxiety (HA), and depression (HD)

According to the univariate analysis or bivariate correlation, we found that age, education level, work status, family income, lymphedema duration, lymphedema severity, and HA and HD scores were significantly correlated with QOL (Table 1).

Descriptive data on FACT-B

The scores of FACT-B and its subscales are summarized in Table 2. The FACT-B score was 95.27 ± 20.14. The scores of various subscales, for example, FWB, BCC, EWB, SWB, and PWB, are from low to high.

Table 2.

Descriptive Data on Functional Assessment of Cancer Therapy-Breast Quality of Life Instrument and the Correlation with Hospital Anxiety and Depression (N = 71)

Questionnaire/subscale	Number of items	Questionnaire/subscale score, M ± SD	Average score of each item, M ± SD	HAD^a
FACT-B	36	95.27 ± 20.14	2.65 ± 0.56	−0.440^**
PWB	7	20.14 ± 4.94	2.88 ± 0.71	−0.304^*
SWB	7	19.61 ± 5.38	2.80 ± 0.77	−0.363^**
EWB	6	16.31 ± 4.62	2.72 ± 0.77	−0.299^*
FWB	7	16.10 ± 6.29	2.30 ± 0.90	−0.523^***
BCC	9	23.11 ± 5.87	2.57 ± 0.65	−0.120

Means Pearson correlation with FACT-B and subscale.

p < 0.05,^**p < 0.01,^***p < 0.001.

BCC, breast cancer additional concerns subscale; EWB, emotional well-being; FWB, functional well-being; HAD, hospital anxiety and depression; PWB, physical well-being; SWB, social well-being.

Linear regression analysis of QOL predictors

The stepwise multiple linear regression was calculated to predict QOL (FACT-B) based on age, education level, work status, family income, lymphedema duration, and lymphedema severity. A significant regression equation (F = 62.76, p < 0.001) was found, with a R² of 0.859 (Table 3). Age, lymphedema severity, and HA score are all important QOL predictors (FACT-B).

Table 3.

Linear Regression Analysis of Quality of Life Predictors

	B	SE B	β	t	p	95% CI
Constant	112.58	8.44		13.33	<0.001	95.72 to 129.43
Lymphedema severity	−15.56	1.64	−0.65	−9.47	<0.001	−18.84 to −12.28
HA	−1.77	0.40	−0.30	−4.41	<0.001	−2.57 to −0.97
Age	0.46	0.14	0.21	3.27	0.002	0.18 to 0.74

CI, confidence interval.

Discussion

Our study shows that the patients with BCRL have lower QOL. The results indicate that age, lymphedema severity, and HA score are the most important QOL predictors, accounting for 85.9% in QOL. To our knowledge, it is the first study to focus on the correlation of QOL with anxiety and depression in the patients with BCRL. In addition, the relevant evidence shows that lymphedema severity affects QOL, despite such impact being controversial.

The QOL of patients with BCRL

In this study, the FACT-B score of patients with BCRL is 95.27 ± 20.14, which is similar to that of Mak et al.¹² (FACT-B+arm subscale score [12.2 ± 4.3] = 112.2 ± 22.2) and Dai and Duan²⁵ (FACT-B score = 92.12 ± 2.54). Their studies compare the QOL of patients with BCRL to those without lymphedema and found that the patients with lymphedema have lower QOL. This suggests that the patients with BCRL in this study had lower QOL. The scores of various subscales, for example, FWB, BCC, EWB, SWB, and PWB, are sorted from low to high by average score of each item.

The FWB subscale is the worst scale. The contents of this subscale are related to work (including work at home). This is consistent with the findings from previous studies, which indicate that BCRL affects work-related physical functions.^26–28 The patients with BCRL need long-term rehabilitation of the affected limb, such as time-consuming manual lymphatic drainage, pressure bandaging, wearing a pressure suit, avoiding lifting heavy objects, protecting skin from injury, keeping arms raised, and so on,^3,4,29 which may affect patients' daily life and work.³⁰

The BCC subscale is the second worst and may be related to the fact that the patients with BCRL not only have to undergo a mastectomy but also face damage to their body image due to swelling of the affected limbs.^31,32

EWB subscale is the third worst. We found that EWB was negatively correlated with hospital anxiety and depression (r = −0.299, p < 0.05). EWB was used to evaluate patients' attitude toward the disease. Patients with anxiety and depression will have a negative attitude toward the disease.

QOL factors of patients with BCRL

Through univariate analysis or bivariate correlation, we found that patients at older age, with higher education level, part-time job, early and mild lymphedema, and less severe anxiety and depression, have better QOL. The results of linear regression analysis indicate that age, lymphedema severity, and anxiety are the most important QOL predictors, accounting for 85.9% in QOL. It is much higher than that in Tsauo et al.'s prediction model.¹⁴

Anxiety and QOL

Anxiety is one of the strongest QOL predictors; the patients with severe anxiety have lower QOL. In this study, the anxiety score of patients with BCRL was 7.06 ± 3.38 and that of 36.6% of the patients with moderate or severe anxiety is 36.6%. This indicates that the anxiety of patients with BCRL is not optimistic. This finding is consistent with previous studies that male patients with BCRL have worse mental problem than female patients without lymphedema.^16,17 Anxiety can affect the physical and mental health of patients and even cause complications by reducing patients' immunity, leading to lower QOL.^33–35 Previous studies show that severe anxiety and depression are associated with lower QOL in breast cancer patients.^18–20 Our study first focused on the correlation of QOL with anxiety and depression in the patients with BCRL.

Lymphedema severity and QOL

Our study shows that patients with severe lymphedema have lower QOL, which is consistent with the conclusions of Mak et al.¹² and Giray and Akyuz.¹⁵ Moderate and severe lymphedema means that patients suffer from more pronounced swelling and more uncomfortable symptoms, which can lead to a difficult situation. Moreover, raising the limbs alone cannot reduce those symptoms, which means that they are more difficult to treat and usually last a lifetime. Lymphedema of Stage III is manifested as lymphostatic elephantiasis, with large distorted swelling area and very hard skin and tissues, which increase the risk of infection or lymphatic leakage. With a large and heavy arm, the patients have a hard time living a daily life, let alone working. The above reasons may explain lower QOL in the patients with severe lymphedema.

However, in Tsauo et al.'s study,¹⁴ they did not consider arm volume as a predictor. Instead, they found that arm symptoms are significantly correlated with QOL. It may be because lymphedema is a multidimensional disease and its signs are not limited to circumferential or volumetric increases in limb size. This indicates that when predicting the QOL of patients with BCRL, it is not enough to use an objective method to assess the degree of lymphedema. The studies of Bulley et al.³⁶ and Mak et al.¹² support this conclusion.

In accordance with the ISL staging system, the delineation of lymphedema severity is based on the size of the affected limb, changes in the skin, and the uncomfortable symptoms of patients, which is commonly used by medical doctors or lymphedema therapists. Our study used the ISL staging system to assess the degree of lymphedema in patients, indicating that lymphedema severity is associated with QOL. Lee et al.¹³ also used the ISL staging system to assess lymphedema severity and its impact on QOL; however, the results are not statistically significant, which may be because the study targets not only BCRL but also leg lymphedema and head and neck lymphedema.

Age and QOL

Older patients have better QOL. One reason for this finding may be that older female patients are less concerned about dissatisfied body image caused by mastectomy or swelling limbs.^32,37 Moreover, older women are more likely to retire or work part-time; the physical damage caused by lymphedema has less impact on work, so they have less job stress.

Implications of clinical practice

Based on the current analysis, it is strongly recommended that future intervention studies be conducted so as to improve QOL in the patients with BCRL.

Recommendations for future intervention studies include: (1) target population: young patients with low education level, full-time job, and low family income; (2) establish a BCRL prevention system to avoid the occurrence or aggravation of BCRL, including (i) primary prevention: strengthen health education during the perioperative period to prevent the occurrence of lymphedema³⁸; (ii) secondary prevention: early detection, diagnosis, and treatment of lymphedema by a multidisciplinary team^39,40; and (iii) tertiary prevention: improving patients' adherence during the rehabilitation period to prevent the recurrence of BCRL; and (3) pay attention to patients' psychological distress: relieving their psychological distress as soon as possible after surgery, strengthening social support, and providing professional psychological counseling when necessary.²²

Limitations

This study has limitations which should be mentioned. First, the number of subjects for this study was relatively small and was conducted in a single cancer center, which may limit the representativeness of patients. Second, the lack of information on the treatment protocols for, among others, chemotherapy and radiotherapy might be the factors affecting QOL. Certainly, there may be other factors which would affect the QOL of patients with BCRL and need to be explored further. Third, there are a number of condition-specific QOL tools for lymphedema of the arm such as LYMQOL-arm, lymph-ICF, and FACT B + 4 for the upper limb. But at the time of this study, the scales have not been translated, so this study adopted the universal scale (FACT-B). We hope to apply the specific QOL scales after translation in our future studies.

Conclusions

The patients with BCRL have lower QOL. Age, lymphedema, and anxiety are the most important QOL predictors. Therefore, it is very important to establish a BCRL prevention system and pay attention to psychological distress in the patients with BCRL.

Footnotes

Acknowledgments

The authors thank all the participants for their valuable contributions to this study.

Ethical Approval

Approval was obtained from the Ethics Committee of Sun Yat-Sen University Cancer Center (No. GYX2020-002). The procedures used in this study are in line with the purpose of the Declaration of Helsinki.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This study was funded by the 2020 Medical Scientific Research Foundation of Guangdong Province of China (A2020088; A2020267).

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