Prospective, early longitudinal assessment of lymphedema-related quality of life among patients with locally advanced breast cancer: The foundation for building a patient-centered screening program

Abstract

Background

We examined how breast cancer-related lymphedema (BCRL) affects health-related quality of life (HRQOL), productivity, and compliance with therapeutic interventions to guide structuring BCRL screening programs.

Methods

We prospectively followed consecutive breast cancer patients who underwent axillary lymph node dissection (ALND) with arm volume screening and measures assessing patient-reported health-related quality of life (HRQOL) and perceptions of BCRL care. Comparisons by BCRL status were made with Mann-Whitney U, Chi-square, Fisher's exact, or t tests. Trends over time from ALND were assessed with linear mixed-effects models.

Results

With a median follow-up of 8 months in 247 patients, 46% self-reported ever having BCRL, a proportion that increased over time. About 73% reported fear of BCRL, which was stable over time. Further in time from ALND, patients were more likely to report that BCRL screening reduced fear. Patient-reported BCRL was associated with higher soft tissue sensation intensity, biobehavioral, and resource concerns, absenteeism, and work/activity impairment. Objectively measured BCRL had fewer associations with outcomes. Most patients reported performing prevention exercises, but compliance decreased over time; patient-reported BCRL was not associated with exercise frequency. Fear of BCRL was positively associated with performing prevention exercises and using compressive garments.

Conclusions

Both incidence and fear of BCRL were high after ALND for breast cancer. Fear was associated with improved therapeutic compliance, but compliance decreased over time. Patient-reported BCRL was more strongly associated with worse HRQOL and productivity than was objective BCRL. Screening programs must support patients’ psychological needs and aim to sustain long-term compliance with recommended interventions.

Highlights

• •Both incidence and fear of BCRL were high after ALND for breast cancer.
• •Fear of BCRL was associated with improved therapeutic compliance.
• •Compliance with preventive/therapeutic interventions decreased over time.
• •Patient-reported BCRL is more strongly associated than objective BCRL with HRQOL.
• •Screening programs must support psychological needs to sustain long-term compliance.

1. Introduction

Breast cancer-related lymphedema (BCRL) is a chronic, debilitating side effect of axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) that negatively affects physical, social, and psychologic function as well as work productivity.[1] BCRL can also pose significant financial costs to patients and the healthcare system.[[2], [3], [4]] Because BCRL has broad effects on breast cancer survivors, the National Comprehensive Cancer Network recommends routine screening for BCRL at follow-up oncologic visits.[5] Although some patients with locally advanced disease can be spared ALND to decrease the risk of BCRL,[6],7 for many, ALND and RNI remain a standard of care, and thus the risks associated with these interventions remain common.

Despite decades of research, understanding the effects of BCRL on patients and how best to communicate with them about risks and the need for preventive and therapeutic strategies remain undefined. The reported incidence of BCRL ranges from 20% to 60.3% among high-risk populations,[[8], [9], [10], [11], [12]] which complicates making informed decisions. Even patients who are satisfied with their oncologic care are less satisfied with information provided on the physical, psychological, and social sequelae of BCRL.[13] The optimal strategy for lymphedema education regarding risks, precautions, signs and symptoms, and exercises to optimize long-term compliance and durability are still unknown, and it is thought that patient worry plays a role in the adoption of risk-reducing behaviors.[14] Disappointingly, one randomized intervention that included education and a visit with a lymphedema specialist showed no difference in the development of lymphedema, which the authors hypothesized was due to poor adherence.[15] An unmet need remains to better understand the reason behind patients’ lack of compliance and to better design patient support that ultimately leads to long-term use of preventive and therapeutic interventions for BCRL.

This study sought to prospectively examine the incidence and sequelae of BCRL in a racially diverse cohort of patients with locally advanced breast cancer who underwent ALND as standard of care. We measured gross arm volume change and examined symptoms, loss of productivity, and compliance with recommended interventions via serial patient-reported outcomes. We sought to evaluate if patient-reported measures of lymphedema correlate better than objective measures of lymphedema with patient-reported deficits in HRQOL in order to assess whether patient perceptions and understanding of their care should guide screening programs as we hypothesized. In seeking to design an optimal lymphedema screening program within an oncology clinic, understanding how lymphedema broadly affects patients and why they discontinue recommended therapy can be a first step toward improving compliance with preventive and therapeutic interventions and improving outcomes.

2. Materials and methods

2.1. Study design

This prospective study was part of a lymphedema screening initiative that was designed to screen breast cancer patients for lymphedema preoperatively and after undergoing ALND among patients who intended to continue postoperative follow-up visits at the Nellie B. Connally Breast Center at The University of Texas MD Anderson Cancer Center (NCT05056207).[16] Part of this initiative included efforts to coordinate a referral to rehabilitative medicine after ALND so that a lymphedema-certified therapist could provide education on lymphedema prevention exercises. Patients were consecutively recruited between 2018 and 2019. Patients received radiotherapy based on guidelines published by the National Comprehensive Cancer Network, and if regional nodal irradiation was delivered it included the undissected axilla, internal mammary nodes, and supraclavicular lymph nodes. Lymphedema screening was performed in coordination with other oncologic follow-up visits at 0–3 months, >3–6 months, >6–9 months, >9–12 months, and >12–16 months postoperatively. At each screening visit, arm volume was measured by perometry by a medical assistant, and patients were asked to complete questionnaires on aspects of BRCL. Patients were advised to wear sleeves/compressive garments by lymphedema-certified therapists if they showed early signs or symptoms of BCRL as part of routine clinical praactice.[17]

2.2. Ethical considerations

All participants voluntarily provided written informed consent to enroll in this institutional review board approved study. All participants received care consistent with standard of care guidelines. Patient confidentiality and privacy were protected as data were de-identified and stored on a secure server at all times. Only essential investigators had access to study data. There was no potential for harm in this survey-based study.

2.3. Patient assessments

Arm volume was documented as the mean of three measurements per upper extremity at each visit, measured with a horizontal Perometer 400NT (Perosystem).[18] Because not all patients had undergone perometry before surgery, changes in arm volume were defined as: (volume affected arm)/(volume unaffected arm) at a given timepoint. Mild-moderate lymphedema was objectively defined as an increase of ≥5% by perometry and/or physical examination findings by an oncologist. Patients were stratified according to having ever self-reported lymphedema and having ever been diagnosed with objective lymphedema during the study period.

The intensity and distress of physical and psychosocial lymphedema symptoms were assessed with the Lymphedema Symptom Intensity and Distress-Arm (LSIDS-A), a validated tool for assessing self-reported arm lymphedema symptoms in breast cancer survivors.[19] Items from the LSIDS-A are grouped into 7 symptom clusters: soft tissue sensation, neurological sensation, function, biobehavioral, resource, sexuality, and activity.[19] The Work Productivity Activity and Impairment (WPAI) questionnaire was used to assess impairment with regard to work within and outside the home due to breast cancer.[20] Responses to questions on the WPAI questionnaire are used to calculate 4 outcomes: absenteeism, presenteeism, overall work impairment due to health, and percent activity impairment due to health. Finally, we used a Lymphedema Screening Initiative Questionnaire (LSIQ) to assess patients’ understanding of lymphedema, their perception and satisfaction with lymphedema screening and physical therapy interventions, and their adherence to lymphedema prevention and treatment-related activities. This questionnaire was developed with feedback from 2 breast cancer advocates with lymphedema and was evaluated for comprehensiveness and comprehensibility by 7 other patients with breast cancer. Cognitive interviewing techniques were also used to ask open-ended questions to determine if other pertinent lymphedema-related items were addressed in the questionnaire and if its wording was appropriate prior to usage in this cohort.

2.4. Statistical analysis

The distributions of clinical, demographic, and therapeutic characteristics were calculated for all enrolled patients and for patient groups stratified by self-reported or objective lymphedema status. Continuous variables are reported as mean (standard deviation [SD]) or median (interquartile range), as appropriate. Categorical variables are reported as counts and percentages. Comparisons between stratified groups were made with a two-sample t-test or Mann-Whitney U test for continuous variables and Chi-square tests or Fisher's exact tests for categorical variables. Trends in patient-reported outcomes over time were assessed with a linear mixed-effects model with random intercepts, accounting for associations between repeated measurements in the same subject. Time was treated as a fixed effect and the subject as a random effect. Associations between WPAI and LSIDS-A and lymphedema status were also tested with a linear mixed-effects model but with lymphedema status as the fixed effect. An “LSIQ ever” variable was created for each LSIQ question to assess the percentage of patients who ever agreed to a particular question across the study window. Associations between the LSIQ-ever variable and ever having self-reported or objective lymphedema was evaluated with Chi-square or Fisher's exact tests. A two-tailed p value of <0.05 was considered statistically significant in all analyses. Statistical analyses were done with R (version 4.1.1).

3. Results

A total of 247 patients were enrolled with a mean number of follow-up lymphedema assessments (including at a minimum either perometry or a patient-reported outcome tool) per patient of 1.55 (median 1, range 1–4). These enrolled patients were identified from a total of 635 patients screened, of whom the remainder did not consent on study for the following reasons: 71 were non-English speakers, 82 had not undergone ALND, 62 declined interest in enrollment and 173 were not able to be contacted in coordination with their medical visit. The mean follow-up time was 8.57 months (median 8 months, range 1–16 months). The majority of patients (91%, n = 244) saw a lymphedema-certified therapist during the study period. Baseline, pre-operative perometry measurements were not available for 92 patients (37%). Almost all patients (236 of 247, 96%) underwent perometry measurements. 100% of patients filled out the WPAI and LSIDS at least once, and all but one patient responded to the LSIQ. 96% of patients (236) responded in the LSIQ to a question regarding self-identification of lymphedema.

3.1. Patient characteristics

Patient demographic, clinical, and pathologic characteristics are summarized in Table 1. Most participants (162 [66%]) were overweight or obese, 27 (11%) identified as Black, 18 (7%) identified as Asian, and 36 (15%) identified as Hispanic. All participants underwent ALND as part of cancer treatment, and the mean number of lymph nodes removed was 22.3. Seventy-five patients (30%) had clinical N2–N3 disease, 204 (83%) underwent mastectomy, and 151 (61%) had some form of breast reconstructive surgery during the study period. Fifteen patients (6%) underwent lymphovenous bypass surgery, for whom 8 underwent this procedure as a preventive intervention and 7 for treatment of lymphedema. Also, 199 patients (81%) received neoadjuvant chemotherapy and 224 (91%) received radiation therapy (Table 1), for whom 96% (214 patients) were treated using standard fractionation radiotherapy.

Table 1.

Demographic, clinical, and pathologic characteristics of patients with breast cancer.

All Patients (N = 247)		Patient-Reported Lymphedemac Mean (SD)			Objective Lymphedemad Mean (SD)
	Mean (SD)	Yes (n = 113)	No (n = 123)	P Value	Yes (n = 84)	No (n = 152)	P Value
Age at consent	50.4 (11.4)	50.8 (11.5)	50.2 (11.4)	0.800	51.0 (11.5)	49.8 (11.3)	0.403
Body mass index	28.5 (6.5)	29.2 (6.8)	28.0 (6.0)	0.151	28.9 (6.8)	28.1 (6.3)	0.331
Number of lymph nodes removed	22.3 (9.2)	23.8 (9.2)	21.1 (8.9)	0.020	23.0 (8.8)	21.9 (9.5)	0.370
Number of involved lymph nodes	4.3 (5.8)	5.3 (6.4)	3.6 (5.2)	0.020	5.8 (7.0)	3.4 (4.7)	0.004
		Patient-Reported Lymphedema No. (%)			Objective Lymphedema No. (%)
	All	Yes	No	P Value	Yes	No	P Value
Race				0.602			0.243
White	181 (73)	84 (74)	90 (73)		63 (75)	111 (73)
Black	27 [11]	14 [12]	10 [8]		6 [7]	19 [12]
Asian/Pacific Islander	18 [7]	7 [6]	10 [8]		5 [6]	12 [8]
Other	20 [8]	8 [7]	12 [10]		10 [12]	9 [6]
N/A	1 [1]	0 (0)	1 [1]		0 (0)	1 [1]
Origin				0.529			0.353
Non-Hispanic	211 (85)	98 (87)	102 (83)		69 (82)	133 (88)
Hispanic	36 [15]	15 [13]	21 [17]		15 [18]	19 [12]
Menopausal Status				0.320			0.898
Premenopausal	98 [21]	39 [22]	52 [23]		33 [24]	64 [23]
Peri-menopausal	9 [4]	6 [5]	3 [2]		3 [4]	5 [3]
Postmenopausal	138 (56)	66 (58)	68 (55)		48 (57)	82 (54)
N/Aa	2 [1]	2 (2)	0 (0)		0 (0)	1 [1]
Body mass index category				0.489			0.232
Underweight	7 [3]	2 [2]	4 [3]		0 (0)	7 [5]
Normal weight	78 [25]	33 [26]	42 [22]		29 [22]	48 [25]
Overweight	70 [27]	30 [28]	36 [26]		25 [29]	40 [28]
Obese	92 [30]	48 (43)	41 [31]		30 [32]	57 [30]
Breast surgery performed				0.420			0.021
Segmental mastectomy	40 [16]	14 [12]	22 [18]		7 [8]	32 [33]
Mastectomy	204 (83)	97 (86)	100 (81)		77 (92)	118 (78)
No breast surgery	3 [1]	2 [2]	1 [1]		0 (0)	2 [1]
Reconstructive surgery performedb				0.410			0.576
Reduction mastopexy + local tissue rearrangement	26 [18]	9 [14]	16 [18]		9 [17]	17 [20]
Tissue expander or implant-based reconstruction	77 (54)	34 (52)	42 (59)		29 (56)	47 (54)
TRAM reconstruction + DIEP reconstruction	48 [22]	25 [34]	23 [25]		20 [34]	26 [29]
Clinical T Status				0.335			0.390
cT0/cTis	15 [6]	6 [5]	9 [7]		5 [6]	8 [5]
cT1	45 [18]	15 [13]	28 [35]		12 [14]	33 [36]
cT2	97 [24]	48 [23]	43 [37]		31 [30]	60 [24]
cT3	43 [17]	22 [20]	20 [16]		15 [18]	26 [17]
cT4	46 [19]	22 [20]	22 [18]		21 [38]	24 [16]
cTx	1 [1]	0 (0)	1 [1]		0 (0)	1 [1]
Clinical N Status				0.754			0.256
N0	46 [19]	17 [15]	26 [33]		12 [14]	33 [36]
N1	126 (51)	59 (52)	61 (50)		47 (56)	74 (49)
N2a	14 [6]	7 [6]	7 [6]		6 [7]	7 [5]
N2b	0 (0)	0 (0)	0 (0)		0 (0)	0 (0)
N3a	35 [14]	16 [14]	18 [15]		9 [11]	23 [15]
N3b	7 [3]	3 [3]	4 [3]		1 [1]	6 [4]
N3c	19 [8]	11 [10]	7 [6]		9 [11]	9 [6]
Receipt of neoadjuvant chemotherapy	199 (81)	92 (81)	97 (79)	0.743	71 (85)	118 (78)	0.272
Receipt of taxanes	219 (89)	100 (89)	110 (89)	0.750	73 (87)	137 (90)	0.084
Receipt of anthracyclines	182 (74)	82 (73)	91 (74)	0.921	65 (77)	109 (72)	0.428
Receipt of radiation	224 (91)	106 (94)	110 (89)	0.331	77 (92)	136 (90)	0.753
Radiation target				0.110			0.056
Breast/chest wall only	27 [11]	7 [6]	17 [14]		7 [8]	19 [13]
Breast/chest wall and lymph nodes	175 (71)	87 (77)	84 (68)		67 (80)	98 (64)
Unknown	22 [9]	12 [11]	9 [7]		3 [4]	19 [13]
No radiation given	23 [9]	7 [6]	13 [11]		7 [8]	16 [10]
Hormone receptor status				0.908			0.522
Positive	170 (69)	78 (69)	83 (68)		60 (71)	101 (66)
Negative	77 [39]	35 [25]	40 [25]		24 [26]	51 [22]
Her2-Neu status				0.599			1
Positive	57 [35]	27 [29]	27 [36]		20 [40]	36 [40]
Negative	190 (77)	86 (76)	96 (78)		64 (76)	116 (76)
Surgical Procedure to Treat Lymphedema				0.026			0.026
Yes	23 [9]	16 [14]	6 [5]		11 [13]	12 [8]
No	214 (91)	97 (86)	117 (95)		73 (87)	140 (92)
Physical/occupational therapy consultation related to breast cancer ever reported by patient				0.046			0.197
Yes	211 (86)	103 (91)	100 (81)		76 (91)	126 (83)
No	35 [14]	10 [9]	23 [19]		8 [9]	25 [17]
Type of physical therapy				0.033			0.017
Intermittent Pneumatic Compression	21 [15]	18 [36]	3 [5]		15 [38]	5 [7]
Compressive bandaging	36 [28]	19 [40]	15 [27]		16 [41]	19 [27]
Compressive sleeve garment	80 (58)	43 (54)	35 (66)		29 (48)	45 (65)

Abbreviations: N/A, not available; TRAM, transverse rectus abdominus muscle; DIEP, deep inferior epigastric artery perforator.

Variability in number of patients responding to questions was present and thus totals in the above table reflect responses and percentages for each question.

^aTwo male patients were coded as “non-applicable” regarding their menopausal status.

^bA total of 22 patients underwent both tissue expander and TRAM/DIEP reconstruction and 1 patient underwent reduction mastopexy and implant-based reconstruction.

^cPatient-Reported Lymphedema based on patient responses in the Lymphedema Screening Initiative Questionnaire.

^dObjective Mild Lymphedema defined as a ≥5% limb volume difference of the affected arm compared to the unaffected arm based on perometer measurements.

3.2. Univariate analysis of factors associated with BCRL status

Patients who self-reported lymphedema were more likely to have a higher number of lymph nodes removed (p = 0.02). Both self-reported and objective lymphedema were associated with a higher number of involved lymph nodes (p = 0.02 and p = 0.004 respectively), having undergone a surgical procedure to treat lymphedema (both p=0.026) and increased likelihood of reporting use of an intermittent pneumatic compression device to treat lymphedema (p = 0.03 and p = 0.02, respectively) (Table 1). Segmental mastectomy was associated with a lower rate of objective lymphedema (p = 0.02).

3.3. Lymphedema diagnosis and knowledge

A total of 113 patients (46%) self-reported having lymphedema at some timepoint (Table 1). Forty-four percent (50) of patients with self-reported lymphedema had objective lymphedema based on perometry measurements. Of patients ever found to have lymphedema based on objective measures, 31 (38%) never had self-reported lymphedema. Among patients who were not found to have lymphedema by objective measures, 59 (41%) still self-reported as having lymphedema. The incidence of patient self-reported lymphedema increased with the follow-up time after surgery, from 19% during 0–3 months after surgery up to 45% after 12 months (p < 0.001) (Table 3). 60% (146 of 245 respondents) reported ever having known about lymphedema before meeting with their medical team, and 92% (226 of 245 respondents) reported that they had ever received education regarding their lifetime risk of lymphedema because of their breast cancer (Table 2). Fear of lymphedema was reported by 178 study respondents (73%) during the follow-up period (Table 2), a proportion that remained relatively stable over time (Table 3). Most patients (232 [95%]) responded that their health concerns about lymphedema were understood (Table 2). Over time, a higher percentage of patients reported being aware of how to identify signs of lymphedema (from 76% to 91%, p = 0.014) (Table 3).

Table 3.

Responses on Lymphedema Screening Initiative Questionnaire over time.

		Time After Surgery
		0–3 months	>3–6 months	>6–9 months	>9–12 months	>12–16 months	P Value
No. (%)		n = 117	n = 116	n = 107	n = 106	n = 70
I have lymphedema							<0.001
Strongly agree/agree		22 [19]	19 [18]	44 (43)	44 (44)	29 (45)
Neutral		12 [11]	18 [18]	15 [15]	11 [11]	8 [12]
Strongly disagree/disagree		80 (70)	66 (64)	43 [23]	46 (45)	28 (43)
Lymphedema knowledge/education,no. (%)
I knew about lymphedema before I met with my breast cancer medical team at MD Anderson							0.269
Strongly agree/agree		62 (53)	56 (48)	51 (48)	42 [21]	35 (50)
Neutral		10 [8]	3 [3]	7 [7]	5 [5]	3 [4]
Strongly disagree/disagree		45 [24]	57 (49)	48 (45)	58 (55)	32 (46)
I was provided with education that prepared me to understand that because of the breast cancer treatments I received, I have a lifetime risk of lymphedema							0.285
Strongly agree/agree		97 (83)	102 (88)	92 (87)	90 (86)	64 (91)
Neutral		8 [7]	4 [3]	3 [3]	1 [1]	3 [4]
Strongly disagree/disagree		12 [10]	10 [9]	11 [10]	14 [13]	3 [4]
I know who to contact if I develop swelling or redness in my arm							0.598
Strongly agree/agree		98 (84)	103 (89)	93 (88)	84 (80)	63 (90)
Neutral		10 [8]	5 [4]	5 [5]	9 [9]	3 [4]
Strongly disagree/disagree		9 [8]	8 [7]	8 [7]	12 [11]	4 [6]
I understand how to identify signs of lymphedema							0.014
Strongly agree/agree		88 (76)	107 (92)	92 (87)	93 (89)	64 (91)
Neutral		16 [14]	6 [5]	10 [9]	6 [6]	6 [9]
Strongly disagree/disagree		11 [10]	3 [3]	4 [4]	6 [6]	0 (0)
I know what exercises/massage to do to treat lymphedema							0.540
Strongly agree/agree		64 (88)	83 (86)	76 (89)	86 (94)	54 (95)
Neutral		1 [1]	3 [3]	2 [2]	0 (0)	1 [2]
Strongly disagree/disagree		8 [11]	11 [11]	7 [8]	6 [6]	2 [3]
I have been provided with education regarding exercises to prevent lymphedema							0.107
Strongly agree/agree		72 (77)	96 (89)	90 (88)	91 (91)	55 (85)
Neutral		4 [4]	5 [5]	5 [5]	3 [3]	4 [6]
Strongly disagree/disagree		17 [18]	7 [6]	7 [7]	6 [6]	6 [9]
Physical/occupational therapy recommendations and adherence over time,no. (%)
On average, I perform exercises to prevent lymphedema
0 days/week		7 [7]	8 [7]	13 [13]	18 [18]	12 [18]	0.002
1–2 days/week		11 [11]	23 [33]	30 [39]	33 [25]	17 [28]
3–4 days/week		25 [38]	30 [41]	21 [33]	16 [16]	14 [33]
5–6 days/week		17 [17]	23 [33]	14 [14]	15 [15]	9 [14]
Every day		39 [24]	26 [40]	20 [20]	20 [20]	14 [33]
I was advised to wear compression garments/bandages
Sometimes		24 [20]	36 [39]	36 [22]	39 [30]	26 [30]	0.038
24 h/day		3 [3]	6 [5]	6 [6]	10 [9]	6 [9]
Not advised to use		90 (77)	72 (63)	63 (60)	57 (54)	37 (53)
Other/unclear		0 (0)	1 [1]	0 (0)	0 (0)	1 [1]
I wear compression garments/bandages
Sometimes		25 [33]	36 [39]	36 [22]	40 [34]	30 (43)	0.092
24 h/day		4 [3]	4 [4]	2 [2]	5 [5]	1 [1]
Never		88 (75)	75 (65)	67 (64)	61 (57)	39 (56)
Satisfaction with care provided,no. (%)
I feel that my health concerns about lymphedema are understood							0.596
Strongly agree/agree		103 (88)	103 (90)	96 (91)	87 (83)	64 (91)
Neutral		6 [5]	7 [6]	6 [6]	10 [9]	4 [8]
Strongly disagree/disagree		8 [7]	5 [4]	3 [3]	8 [8]	2 [3]
I have a fear of developing lymphedema							0.620
Strongly agree/agree		84 (72)	78 (68)	64 (61)	71 (69)	45 (65)
Neutral		24 [33]	24 [33]	25 [40]	18 [17]	14 [20]
Strongly disagree/disagree		8 [7]	13 [11]	16 [15]	14 [14]	10 [15]
The breast cancer medical team at MD Anderson helped alleviate my fears about lymphedema							0.011
Strongly agree/agree		59 (50)	78 (67)	68 (64)	65 (63)	45 (64)
Neutral		53 (45)	27 [35]	30 [27]	27 [28]	18 [28]
Strongly disagree/disagree		5 [4]	11 [10]	8 [8]	13 [12]	7 [10]
The breast cancer medical team at MD Anderson answered my questions about lymphedema							0.073
Strongly agree/agree		96 (82)	107 (92)	94 (89)	93 (89)	61 (87)
Neutral		19 [16]	4 [3]	9 [8]	7 [7]	7 [10]
Strongly disagree/disagree		2 [2]	5 [4]	3 [3]	5 [5]	2 [3]
If you've had a perometer measurement, the results were explained during the clinic visit							0.182
Strongly agree/agree		71 (67)	87 (76)	81 (79)	81 (78)	58 (87)
Neutral		12 [11]	8 [7]	6 [6]	7 [7]	5 [7]
Strongly disagree/disagree		23 [36]	19 [17]	15 [15]	16 [15]	4 [6]
I have had a consultation with a physical or occupational therapist related to my breast cancer							0.022
Agree		80 (71)	102 (88)	88 (85)	94 (89)	60 (86)
Disagree		25 [36]	10 [9]	11 [11]	10 [9]	8 [11]
Cannot recall		8 [7]	4 [3]	5 [5]	2 [2]	2 [3]
I am satisfied with the cancer care I receive							0.573
Strongly agree/agree		105 (90)	110 (95)	100 (93)	99 (93)	67 (96)
Neutral		6 [5]	5 [4]	3 [3]	3 [3]	3 [4]
Strongly disagree/disagree		5 [4]	1 [1]	4 [4]	4 [4]	0 (0)
I am satisfied with the physical/occupational therapy care I receive/have received (among who agree had consulted PT)							0.876
Strongly agree/agree		64 (93)	84 (88)	75 (87)	84 (92)	54 (92)
Neutral		2 [3]	4 [4]	6 [7]	4 [4]	3 [5]
Strongly disagree/disagree		3 [4]	7 [7]	5 [6]	3 [3]	2 [3]

	Time After Surgery
	0–3 months	>3–6 months	>6–9 months	>9–12 months	>12–16 months	P Value
	n = 117	n = 116	n = 107	n = 106	n = 70
Perspectives on lymphedema screening,no. (%)
Lymphedema screening with a perometer when added onto my other medical visits is worth it to me						0.495
Strongly agree/agree	113 (97)	111 (96)	100 (94)	98 (93)	65 (93)
Neutral	4 [3]	5 [4]	4 [4]	5 [5]	5 [7]
Strongly disagree/disagree	0 (0)	0 (0)	2 [2]	2 [2]	0 (0)
The lymphedema screening I receive helps alleviate my fear of developing lymphedema						0.048
Strongly agree/agree	79 (69)	88 (76)	72 (68)	77 (73)	55 (79)
Neutral	33 [26]	17 [15]	21 [20]	19 [18]	10 [14]
Strongly disagree/disagree	3 [3]	11 [9]	13 [12]	10 [9]	5 [7]
I feel that lymphedema screening with the perometer should be performed at each of my visits at the Breast Center						0.292
Strongly agree/agree	96 (83)	85 (74)	79 (74)	88 (83)	54 (77)
Neutral	17 [15]	22 [19]	21 [20]	14 [13]	15 [33]
Strongly disagree/disagree	2 [2]	8 [7]	6 [6]	4 [4]	1 [1]
I have lymphedema						<0.001
Strongly agree/agree	22 [19]	19 [18]	44 (43)	44 (44)	29 (45)
Neutral	12 [11]	18 [18]	15 [15]	11 [11]	8 [12]
Strongly disagree/disagree	80 (70)	66 (64)	43 [23]	46 (45)	28 (43)

Abbreviations: PT, physical therapy.

Table 2.

Overall responses to the Lymphedema Screening Initiative Questionnaire.

	Overall	Patient-Reported Lymphedemaa			Objective Mild Lymphedemab
		Yes	No	P Value	Yes	No	P Value
	No. (%)	(n = 113)	(n = 122)		(n = 83)	(n = 151)
I knew about lymphedema before I met with my breast cancer medical team at MD Anderson				0.464			0.206
Ever agreed	146 (60)	72 (64)	71 (58)		54 (65)	84 (56)
Never agreed	99 [21]	41 [32]	51 [23]		29 [37]	67 (44)
I was provided with education that prepared me to understand that because of the breast cancer treatments I received I have a lifetime risk of lymphedema.				1			1
Ever agreed	226 (92)	105 (93)	113 (93)		76 (92)	139 (92)
Never agreed	19 [8]	8 [7]	9 [7]		7 [8]	12 [8]
I feel that my health concerns about lymphedema are understood				0.454			1
Ever agreed	232 (95)	106 (94)	118 (97)		78 (94)	143 (95)
Never agreed	13 [5]	7 [6]	4 [3]		5 [6]	8 [5]
I have a fear of developing lymphedema				0.062			0.188
Ever agreed	178 (73)	90 (80)	84 (69)		65 (78)	104 (69)
Never agreed	66 [41]	22 [20]	38 [39]		18 [36]	46 [39]
The breast cancer medical team at MD Anderson helped alleviate my fears about lymphedema				0.815			1
Ever agreed	179 (73)	84 (74)	88 (72)		60 (72)	109 (72)
Never agreed	66 [41]	29 [28]	34 [27]		23 [27]	42 [27]
The breast cancer medical team at MD Anderson answered my questions about lymphedema				0.734			0.567
Ever agreed	227 (93)	106 (94)	112 (92)		75 (90)	141 (93)
Never agreed	18 [7]	7 [6]	10 [8]		8 [10]	10 [7]
I know who to contact if I develop swelling or redness in my arm				0.429			1
Ever agreed	217 (89)	102 (90)	105 (86)		74 (89)	134 (89)
Never agreed	28 [11]	11 [10]	17 [14]		9 [11]	17 [11]
Lymphedema screening with a perometer when added onto my other medical visits is worth it to me				1			1
Ever agreed	235 (96)	109 (97)	117 (96)		79 (95)	145 (96)
Never agreed	10 [4]	4 [3]	5 [4]		4 [5]	6 [4]
If you've had a perometer measurement, the results were explained during the clinic visit				0.240			0.197
Ever agreed	205 (86)	100 (89)	98 (83)		68 (82)	129 (89)
Never agreed	34 [14]	12 [11]	20 [17]		15 [18]	16 [11]
The lymphedema screening I receive helps alleviate my fear of developing lymphedema				0.248			0.480
Ever agreed	199 (81)	89 (79)	105 (85)		65 (77)	124 (82)
Never agreed	47 [19]	24 [33]	18 [15]		19 [35]	27 [18]
I feel that lymphedema screening with the perometer should be performed at each of my visits at the Breast Center				0.835			0.260
Ever agreed	201 (82)	94 (83)	100 (81)		72 (86)	119 (79)
Never agreed	45 [18]	19 [17]	23 [19]		12 [14]	32 [33]
I understand how to identify signs of lymphedema				0.043			1
Ever agreed	226 (92)	109 (96)	109 (89)		77 (92)	139 (92)
Never agreed	20 [8]	4 [4]	14 [11]		7 [8]	12 [8]
I have lymphedema				<0.001			0.004
Ever agreed	113 (48)	113 (100)	0 (0)		50 (62)	59 [42]
Never agreed	123 (52)	0 (0)	123 (100)		31 [34]	85 (59)
I have had a consultation with a physical or occupational therapist related to my breast cancer				0.046			0.197
Ever agreed	211 (86)	103 (91)	100 (81)		76 (91)	126 (83)
Never agreed	35 [14]	10 [9]	23 [19]		8 [9]	25 [17]
I am satisfied with the physical/occupational therapy care I receive/have received (among those who have had a consult)				0.606			0.503
Ever agreed	191 (94)	94 (93)	91 (96)		72 (97)	112 (93)
Never agreed	13 [6]	7 [7]	4 [4]		3 [4]	9 [7]
I know what exercises/massage to do to treat lymphedema.				0.338			0.386
Ever agreed	193 (95)	92 (93)	95 (97)		72 (97)	113 (93)
Never agreed	10 [5]	7 [7]	3 [3]		2 [3]	8 [7]
I have been provided with education regarding exercises to prevent lymphedema				0.156			0.055
Ever agreed	208 (89)	102 (93)	98 (86)		75 (95)	124 (86)
Never agreed	26 [11]	8 [7]	16 [14]		4 [5]	21 [14]
On average, I perform exercises to prevent lymphedema				0.751			0.293
Ever agreed (sometimes perform exercises)	190 (80)	88 (81)	93 (78)		61 (76)	122 (83)
Never agreed (never performed exercises)	47 [20]	21 [19]	26 [36]		19 [40]	25 [17]
I was advised to wear compression garments/bandages				<0.001			0.013
Ever advised to use	114 (47)	69 (61)	43 [37]		48 (57)	59 [24]
Never advised to use	131 (53)	44 [24]	79 (65)		36 (43)	91 (61)
I wear compression garments/bandages				<0.001			0.025
Ever wear	95 (83)	67 (59)	39 [25]		46 (55)	58 [24]
Never wear	19 [17]	46 [42]	83 (68)		38 (45)	92 (63)
I am satisfied with the cancer care I receive				0.338			0.469
Ever agreed	236 (96)	111 (98%)	117 (95)		82 (98)	143 (95)
Never agreed	10 [4]	2 (2%)	6 [5]		2 [2]	8 [5]

^aPatient-Reported Lymphedema based on responses in the Lymphedema Screening Initiative Quesionnaire.

^bObjective Mild Lymphedema defined as a ≥5% limb volume difference of the affected arm compared to the unaffected arm based on perometer measurements.

3.4. Lymphedema treatment recommendations and patient-reported compliance

More than half of patients reported knowing about lymphedema prior to meeting their breast cancer team (146 [60% of 245 respondents]). Most patients (208 [89% of 234 respondents]) reported having been provided with education at some point about exercises to prevent lymphedema (Table 2) 17. Most patients reported performing lymphedema-prevention exercises, although the proportion of patients performing none of these exercises increased over time from 7% to 18%, and the proportion of patients reporting performing lymphedema prevention exercises daily decreased from 39% to 21% (p = 0.002) (Table 3). No association was found between either patient-reported lymphedema (p = 0.751) or objective, mild-moderate lymphedema (p = 0.293) and self-reported performance of exercise to prevent lymphedema (Table 2). Fear of lymphedema was associated with exercise compliance, with 161 patients (92% of 175) ever expressing fear of lymphedema performing preventive exercises vs. 48 patients (80% of 60) among those who did not (p = 0.02). Both patient-reported lymphedema and objective, mild-moderate lymphedema were associated with having been advised to use a compressive garment and ever wearing one (both p < 0.001). Most patients (95 [83% of 114]) who recalled ever having been advised to wear a compressive sleeve/garment reported having worn these at some point during the study period (Table 2). Fear of lymphedema was more prevalent among those patients who reported ever having worn a compressive sleeve/garment compared to those who did not wear those garments (51% vs 28%, p = 0.002).

3.5. Symptoms and productivity impairment associations with lymphedema

Upper-extremity symptoms related to soft tissue sensation intensity, neurological sensation, function, and activity were reported to be worst within 3 months of surgery and improved thereafter during the study period (Table 4). Reports of biobehavioral, resource, and sexuality concerns were stable during the study period. Patient-reported lymphedema was associated with a higher incidence of patient-reported soft tissue sensation concerns (p < 0.001), biobehavioral concerns (p = 0.006), and resource/insurance concerns (p = 0.001) but not with patient-reported problems regarding physical function, sexuality, or general activity (Supplemental Table 1). The intensity (p = 0.042) and distress (p = 0.001) associated with changes in neurological sensation were worse among those with self-reported lymphedema. Objective, mild-moderate lymphedema was also associated with soft tissue sensation concerns (p = 0.025), including related intensity (p = 0.017) and distress (p = 0.008), but not with any other symptoms or measures of work and activity impairment (Supplemental Table 1).

Table 4.

Lymphedema symptoms after surgery: Lymphedema Symptom Intensity Distress – Arm Report.

		Time Period After Surgery
		0–3 mo	>3–6 mo	>6–9 mo	>9–12 mo	>12–16 mo
		(n=87)	(n=88)	(n=109)	(n=105)	(n=69)
Cluster	No. of Symptoms in Cluster	Mean (SD)	Mean (SD)	Mean (SD)	Mean (SD)	Mean (SD)	P Valuea
Overall	30	3.7 (1.6)	3.4 (1.8)	3.3 (2.0)	3.3 (1.9)	3.2 (1.8)	<0.001
Soft Tissue Sensation	4	1.3 (1.3)	1.4 (1.1)	1.6 (1.3)	1.8 (1.4)	1.6 (1.3)	0.018
Intensity		2.2 (1.0)	2.1 (1.0)	2.1 (0.9)	2.0 (1.0)	1.7 (0.9)	0.009
Distress		1.7 (0.9)	1.7 (0.9)	1.7 (0.8)	1.8 (1.1)	1.7 (1.0)	0.901
Neurological Sensation	7	2.2 (1.8)	1.8 (1.8)	1.8 (1.7)	1.8 (1.8)	1.6 (1.6)	0.010
Intensity		2.2 (1.0)	2.1 (0.9)	2.1 (1.1)	2.0 (1.1)	1.9 (0.9)	0.054
Distress		1.6 (0.9)	1.8 (0.9)	1.8 (0.9)	1.7 (1.1)	1.7 (1.0)	0.551
Function	2	0.9 (0.8)	0.5 (0.8)	0.7 (0.8)	0.6 (0.7)	0.5 (0.7)	0.005
Intensity		2.6 (1.2)	1.9 (1.1)	2.4 (1.2)	2.0 (1.2)	1.9 (1.1)	0.007
Distress		2.1 (1.2)	1.7 (1.0)	2.0 (1.1)	1.9 (1.1)	1.8 (1.1)	0.611
Biobehavioral	9	2.8 (2.3)	3.1 (2.4)	3.1 (2.5)	3.0 (2.3)	2.7 (2.4)	0.700
Intensity		2.3 (1.0)	2.6 (1.0)	2.4 (1.0)	2.1 (0.9)	2.2 (1.0)	0.025
Distress		2.1 (1.0)	2.2 (1.0)	2.2 (1.0)	2.0 (1.0)	2.2 (1.0)	0.589
Resource	2	0.2 (0.5)	0.1 (0.4)	0.1 (0.5)	0.2 (0.5)	0.2 (0.6)	0.474
Intensity		2.8 (1.1)	2.3 (0.4)	3.0 (1.5)	3.0 (1.5)	2.6 (1.4)	0.978
Distress		2.5 (1.0)	2.5 (0.5)	2.7 (1.5)	2.8 (1.5)	2.6 (1.0)	0.605
Sexuality	3	1.0 (1.4)	1.3 (1.6)	1.5 (1.7)	1.3 (1.5)	1.1 (1.4)	0.154
Intensity		3.0 (1.2)	3.1 (1.4)	3.2 (1.6)	3.0 (1.4)	3.1 (1.4)	0.268
Distress		2.6 (1.3)	3.1 (1.4)	3.1 (1.5)	3.0 (1.4)	3.1 (1.4)	0.079
Activity	3	0.8 (0.8)	0.8 (0.8)	0.5 (0.8)	0.5 (0.7)	0.5 (0.7)	<0.001
Intensity		2.7 (1.1)	2.5 (1.1)	2.6 (1.3)	2.7 (1.2)	2.5 (0.9)	0.901
Distress		2.4 (1.2)	2.3 (1.1)	2.7 (1.2)	2.5 (1.1)	2.2 (1.1)	0.383

^aDerived from linear mixed-effects model.

Work productivity factors including absenteeism, presenteeism, overall work impairment, and activity impairment all improved after the immediate postoperative period, as did patient-reported loss of productivity (Supplemental Table 2). At 12–16 months after ALND, breast cancer-associated side effects had not fully resolved with regard to regular daily activities, work productivity, or hours missed from work. We found statistically significant positive associations between patient self-reported lymphedema and absenteeism (p = 0.039), work impairment (p = 0.043), and activity impairment (p = 0.006) (Supplemental Table 1). Patients requiring more intensive lymphedema treatments such as intermittent pneumatic compression (IPC) at 9–12 months after surgery had greater work impairment than those using compressive garments or bandaging (p = 0.026), whereas no such association was found in the immediate (0–3 months) postoperative period (p = 0.747). Worse impairment in productivity measured by the WPAI and worse soft tissue, neurological, biobehavioral, and resource/insurance concerns measured by the LSIDS-A were seen among those with self-reported lymphedema, whereas fewer such correlations were noted among those with an objective diagnosis (perometer and physical examination–based) (Supplemental Table 1). There was no association between patient-reported nor objective lymphedema and fear of lymphedema (Table 2).

3.6. Patient impressions of their care team

Patients reported a high level of satisfaction with their overall cancer care (96% [236 of 246 patients]) and physical/occupational therapy care (94% [191 of 204 patients who saw a therapist]), neither of which varied by lymphedema status (p = 0.338 and p = 0.606, respectively, Table 2). Most patients (227 [93%]) stated that their medical team answered their questions about lymphedema (Table 2); 199 patients (81%) reported that the lymphedema screening received helped alleviated their fears of lymphedema, and 179 (73%) reported that the medical team did (Table 2).

4. Discussion

Although screening for lymphedema is a first step toward appropriate referral for treatment interventions, how best to do this to support preventive and therapeutic interventions and to meet patients’ broader lymphedema-related concerns has been under-studied. We sought to define patient-reported lymphedema symptoms in a cohort at high risk of developing lymphedema. Interestingly, in our study, although the number of lymph nodes removed was not correlated with the presence of objective lymphedema, the number of positive lymph nodes was strongly correlated with the presence of objective lymphedema (Table 1), suggesting that the location and pathology of affected nodes may play a larger role in objective lymphedema development. Additionally, this study was unique in identifying a lack of association between obesity and presence of lymphedema (Table 1) because lymphedema has been consistently shown to be associated with obesity [[33], [35], [36], [40]]. The lack of significant associations between patient-reported or objective lymphedema status and most variables (Table 1) suggests that it is difficult to predict who will suffer from lymphedema among patients undergoing ALND. Thus, it is more important than ever to understand potential motivators for patient compliance with preventive and therapeutic interventions.

Our study included 247 patients, a sample size which is similar to or greater than that of similar studies investigating associations with BCRL [37], 21, 23. Though estimates of the incidence of BCRL vary widely [[8], [9], [10], [11], [12]], the results from this study suggest that BCRL is more common than previous conservative estimates. This may be explained in part by the variety of definitions of BCRL used in various studies. However, this study found that the incidence of BCRL was high as defined both by patient-report and objective measurement, especially in this racially diverse cohort. We provide a contemporary assessment of the impact of lymphedema on patient reported outcomes within the first year of axillary lymph node dissection. We identified that changes in work impairment, soft tissue and neurological sensations, and financial concerns were all associated with patient-reported lymphedema, items which should be particularly targeted in lymphedema screening efforts. This was the first study to examine the role of patient reported fear of lymphedema and its impact on noncompliance with BCRL interventions. Knowledge of preventive exercises was not associated with increased utilization of these preventive interventions, highlighting the importance of not only evaluating alternative prevention interventions but also determining means to increase patient adherence. Based on our findings, we propose that greater psychosocial supports for breast cancer patients following ALND during their oncology follow-up visits will be important for improving lymphedema outcomes.

Lymphedema may cause or exacerbate emotional distress,[5],38 and those with greater lymphedema-related distress have been found to have worse physical and mental health outcomes.[[5], [27], [28], [41]] Guidelines suggest that clinical monitoring of breast cancer survivors should include psychosocial assessment,[5] and our study identified several key areas in which a lymphedema screening program should target psychosocial support for patients, including addressing high and persistent fear of lymphedema. The associations we found between symptom domains and objective versus patient-reported diagnoses of lymphedema also highlight the importance of including patient symptomatology as a key component of lymphedema screening.

Facilitating patient compliance with both preventive and therapeutic interventions to target BCRL are critical to improving long-term outcomes for patients, as better compliance to BCRL self-care modalities such as wearing compression garments and performing therapeutic exercises has been shown to be associated with prolonged maintenance of arm volume and subsequently decreased BCRL progression [26]. However, preventive exercise compliance decreased over time since ALND in this study. The CALGB70305 trial reported no difference in lymphedema outcomes between education only and a focused education and prevention intervention;[15] while the authors posited that poor adherence may have been the cause of this lack of benefit, a gold standard in prevention interventions has yet to be defined. Others have also found that a greater understanding of BCRL risk management may be associated with better adherence to recommended therapeutic and preventive strategies,[29] as has providing refresher information in the clinic months after surgery.[39] Better understanding of factors regarding patient compliance over time with recommended therapies will be a key component to future trials examining preventive interventions. We found that fear of BCRL was associated with a higher incidence of patient-reported compliance with pursuing exercises and therapies to prevent or treat lymphedema. However, preventive exercise compliance still decreased over time since ALND. While fear and psychosocial factors likely play a major role, these results show that fear alone may not be driving adherence to exercises and therapeutic garment use. Complex interactions between fear, satisfaction with lymphedema-related care, and understanding of personalized risk and sequelae of developing BCRL may play a role in how patients perceive the burden of BCRL; this may impact their motivation and adherence to interventions that have been shown to be effective [26]. A recent qualitative study examining patient experiences with BCRL highlighted the importance of healthcare professionals providing appropriate support for self-management of lymphedema,[25] and our study lends further credence to the need for additional supports for patients in the clinic.

In our study, patient-reported lymphedema appeared to have greater correlation with physical and emotional impairments compared to objective measures of lymphedema, which highlights the need for improved methods for diagnosis BCRL. This brings in to question the role of the objectively measured lymphedema in the absence of patient reported symptoms as a part of screening programs, as a sizable percent of participants with objective lymphedema did not self-report lymphedema. Coupled with the fact that patient-reported lymphedema was more strongly associated with several outcome measures including symptoms and activity impairment, this suggests that patient-report of lymphedema should play a bigger role in lymphedema screening going forward. Published data on lymphedema incidence and patient-reported outcomes present patients and providers with a broad range of expectations. In the Alliance Z1071 study of 488 patients who underwent ALND and developed lymphedema, the 12-month cumulative incidence of lymphedema (quantified as a ≥10% increase in limb volume) was 30.7% (95% CI 26.4–35.8), while 12.0% (95% CI 9.1–15.8) and 13.6% (95% CI 10.5–17.6) of patients reported symptoms of heaviness or swelling at that time, respectively.[9] A group of 263 patients followed prospectively at Massachusetts General Hospital after ALND and RNI reported a 5-year cumulative incidence of moderate, objective lymphedema, defined as a relative limb volume change compared to preoperative baseline of ≥10%, of 30.1%, with a 12-month value of approximately 10%.[31] Our 12-month values (using a mild-moderate limb volume difference comparing the affected to the unaffected limb of >5%) were higher for objectively measured lymphedema (36%) and could reflect that our cohort was at a higher risk of developing lymphedema based on their stage of disease and oncologic interventions required. Patients even with minimal limb volume changes have still been found to have impaired health-related quality of life (HRQOL),[22] and others have found that upper extremity limb volumetric changes and grossly observed lymphatic changes do not sufficiently capture the burden faced from the patient perspective with regard to HRQOL.[37] Newer patient-reported outcome tools that measure arm lymphedema outcomes have emerged [32] and may help to better understand how BCRL fully affects patients. In our study, lymphedema symptoms were the worst during the earliest time period (Table 4). Though some of these observed effects may be due to peri-operative inflammation, the early timepoint was not excluded from analysis because of the importance of understanding the holistic patient experience with regards to their symptoms and how they experience lymphedema post-ALND. Our findings may also underscore the need for more sensitive means of diagnosing early-onset BCRL, including both external and internal physiological assessments.[30],34 Further, additional study is needed to manage the subjective symptoms of those without objective findings.

Our study had multiple limitations. Pre-operative perometry measurements were not available for 37.2% of patients, so comparisons were made between affected and unaffected arm rather than to a pre-operative baseline. This limitation may have impacted the diagnosis of objective lymphedema, as a non-trivial proportion of patients have been found to have asymmetry in the upper extremity volume at the time of diagnosis, prior to any local-regional intervention,[34] and as such, this may have impacted our diagnosis of objective lymphedema. Patients were followed for approximately 1 year after ALND, and thus the chronic effects of BCRL, which likely peak after that first year, [8],10,24,21 were not measured, meaning that we could not determine if earlier-onset patient-reported BCRL was ultimately associated with grossly observed BCRL later after surgery, as has been reported in the literature. [21] Chronic lymphedema is quite likely to affect work productivity [42],23 and overall symptoms, and we could not discern those effects. Additionally, numerous other diagnosis and treatment-related factors outside of lymphedema can affect productivity and work impairment (Supplemental Table 2), and thus any observed effects likely cannot be attributed to lymphedema alone. Many patients also only had one assessment, which makes it challenging to interpret patterns in outcomes over time post-operatively. Second, we did not assess lymphedema (either by self-report or objective measures) nor patient-reported outcomes before any oncologic intervention had begun, making it impossible to conclude whether patients returned to their baseline status. Third, there is the potential for sampling bias because our population included high numbers of patients at high risk of developing lymphedema because of extensive ALND and having received RNI. This complicates commenting on outcomes in a more varied patient population. Fourth, it is also possible that an intervention involving patient-reported outcome measures inquiring about lymphedema-related symptoms may in and of itself have impacted patients’ thoughts and fears around lymphedema. Additionally, the structure of the questions used when assessing patient-reported outcomes (agree/disagree) could have introduced acquiescence bias, thus potentially overestimating the effect size of various outcome variables.

5. Conclusions

In our high-risk cohort of patients with locally advanced breast cancer, nearly half reported having lymphedema after ALND and almost three-quarters reported fear of lymphedema. Patient-reported BCRL seemed to be more strongly associated with impairment in work productivity and decreased HRQOL than were objective measures of lymphedema. Fear of BCRL seems to drive patient compliance with preventive and therapeutic interventions and adherence wanes over time, all of which are factors that need to be incorporated in screening and preventive interventions. Additional strategies are needed to develop effective lymphedema patient screening, including screening for patient-report of their lymphedema status, as objectively measured lymphedema alone may miss many patients with impairment and other distress and symptoms. Screening programs must also focus on better supporting patients’ psychological and functional needs to improve long-term compliance with at-home interventions and to improve HRQOL outcomes.

Funding

This study was supported by a Hearst Clinical Innovator Award from the University of Texas MD Anderson Cancer Center and the Center for Radiation Oncology Research, from support of the AIM Shared Resource, and received an Early Career Oncologist Award from the 104th Annual ARS Meeting.

Declaration of competing interest

SFS has funding from the Emerson Collective Foundation and contracted research agreements with Alpha Tau, Exact Sciences, TAE Life Sciences, and Artios Pharmaceuticals. WAW receives personal fees from Exact Sciences and Epic Sciences. BDS has grant funding from Varian Medical Systems and royalty and equity interest in Oncora Medical. RL serves as a consultant for Monte Rosa Therapeutics.

Appendix ASupplementary data

The following is the Supplementary data to this article: