Attaining the best health possible after breast cancer treatment remains an ongoing challenge since more than 50% of breast cancer survivors suffer from daily distressing symptoms related to lymphedema [hereafter, lymphedema symptoms] even years after cancer treatment. Lymphedema, a chronic abnormal accumulation of lymph fluid in the ipsilateral body area or upper limb, is a chronic condition for more than 40% of 3.1 million breast cancer survivors in the United States. Currently, no surgical or medical interventions at present can cure lymphedema. Lymphedema has been linked to detrimental patient-centered outcomes, such as disability and psychological distress. Lymphedema symptoms are complex in multitude that encompasses more than 20 symptom of arm/hand swelling, breast swelling, chest wall swelling, heaviness, firmness, tightness, stiffness, pain/aching/soreness, tenderness, fibrosis, hotness, redness, numbness, burning, stabbing, tingling, arm fatigue, arm weakness, and limited movement in shoulder, arm, elbow, wrist/fingers. Little is known about lymphedema symptoms and their association with phenotypic characterization of demographics and clinical factors, physiological outcomes of limb volume and lymph fluid level, and patient-centered outcomes of daily function, social, and affective wellbeing. The purpose of this study was to determine whether latent class analysis (LCA) would aid in the identification of lymphedema symptom patterns and associations with phenotypic characterization of demographics and clinical factors, physiological outcomes of limb volume and lymph fluid level, and patient-centered outcomes of daily function, social, and affective wellbeing.
Methods
A prospective, descriptive and repeated-measure design was used to enroll 140 women at pre-surgery and followed at 4-8 weeks and 12 months post-surgery. Lymphedema symptoms and patient-centered outcomes of daily function, social, and affective wellbeing were evaluated using a reliable and valid instrument. Limb volume was measured by a perometer and lymph fluid by a bioimpedance device.
Latent class analysis (LCA) was used to identify classes of lymphedema symptoms to better understand patterns of lymphedema symptoms and associations with phenotypic characterization of demographics and clinical factors, physiological outcomes of limb volume and lymph fluid level, and patient-centered outcomes of daily function, social, and affective wellbeing. Logistic regressions were used to explore the association of latent class of lymphedema symptoms with categorical demographic and clinical variables. ANOVAs and post-hoc pairwise comparison test with a Bonferroni correction for multiple comparisons at the 5% alpha level were used to explore the association of latent class of lymphedema symptoms with limb volume and lymph fluid level as well as patient-centered outcomes of daily function, social, and affective wellbeing.
Results
LCA identified three distinct lymphedema symptom classes at 12-month post-surgery: (1) a low symptom class (mean 1.2 symptoms) consisting primarily of numbness (29%) and tingling (28%); (2) a moderate symptom class (mean 5.9 symptoms), with higher than average prevalence of the arm tightness (58%) and the arm heaviness (44%); and (3) a severe symptom class (mean 14.0 symptoms), with a higher than average prevalence of the limited limb mobility, fluid accumulation and the pain/discomfort symptom factors. The moderate symptom class was the largest (44%), followed by the low symptom class (39%) and the severe symptom class (16%).
Lower level of education, having chemotherapy and radiation therapy were associated with moderate and severe symptom class. The moderate and severe symptom classes were associated with clinical phenotypes of higher lymph volume change and higher bioimpedance ratio (L-Dex). Patients in the severe symptom class are more likely to have a greater than 5% lymph volume increase (a criterion for a diagnosis of lymphedema) between post-surgery and pre-surgery (p = 0.024) and between 12-month follow-up and pre-surgery (p < 0.001). In terms of lymph fluid levels, patients in the severe symptom class are more likely to have a greater than 7.1 L-Dex bioimpedance ratio (a criterion for a diagnosis of lymphedema) at post-surgery (p = 0.037) and 12-month follow-up (p < 0.001).
Poor daily living, social and affective wellbeing are associated with moderate and severe symptom classes in terms of daily living, affective wellbeing, self-perception, sleep disturbance, working outside the home and days absent from work. While patients in the severe symptom class had severe impairment of patient-centered outcomes, it is important to note that the moderate symptom group had significant impairment in comparison with low symptom group in terms of patient-centered outcomes: daily living, affective wellbeing, self-perception, sleep disturbance, working outside the home and days absent from work.
Conclusion
LCA incorporating an overall count of different lymphedema symptoms detected three distinct lymphedema symptom profiles. The data illustrates that the complexity of lymphedema symptom factors that must be accounted for, both in advancing the symptom science in understanding the complexity and heterogeneity of lymphedema symptomatology to predict patient subtypes for impaired physiological outcomes of limb volume and lymph fluid level as well as impaired patient-centered outcomes of daily function, social and affective wellbeing. Early intervention for lymphedema symptoms are needed for prevent patients in the moderate symptom class from progressing into severe symptom class since even the moderate symptom class has significant impairment in terms of patient-centered outcomes of daily living, emotional wellbeing, self-perception, sleep disturbance, working outside the home and days absent from work.
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