Breast cancer related lymphedema (BCRL) at the arm and/or trunk is an extremely dreaded complication after breast cancer treatment due to its chronicity and impact.
The incidence of objective arm and trunk/ breast BCRL is declining due to the major shift into the treatment approach of breast cancer. However, many patients report a sensation of swelling without the presence of objective BCRL, referred to as subjective BCRL. Therefore, subjective BCRL is defined as the diagnosis of BCRL based on the patient's sensation of a difference in size at the arm and/or trunk without the presence of objective BCRL.
At this moment, there is no clear information on the prevalence and the transitions between different BCRL states (no-subjective-objective) over time, as well as about the underlying mechanisms and contributing factors of subjective BCRL. Therefore, the investigators hypothesize that four mechanisms might be associated with the presence and severity of subjective arm or trunk/breast BCRL, including the presence and/ or severity of lymphatic (1) and sensory processing problems (nociceptive (2), neuropathic (3), and/or central sensory processing problems (4)).
The investigators will set up a prospective longitudinal study with breast cancer patients to determine the prevalence of subjective and objective arm or trunk/ breast BCRL at 1, 6, and 12 month(s) post-surgery and the transitions between different BCRL states (no-subjective-objective BCRL) (AIM 1). In addition, factors related to four potential underlying mechanisms (lymphatic, nociceptive, neuropathic, and central sensory processing problems) that contribute to the occurrence of subjective BCRL in comparison to no self-reported swelling and objective BCRL will be determined (AIM 2). Furthermore, the present study will be undertaken to determine factors related to these four underlying mechanisms that contribute to the severity of subjective BCRL at arm or trunk/ breast BCRL within the group of patients with subjective BCRL at different time-points after surgery (at 1, 6, and 12 month(s) post-surgery) (AIM 3).
adults (men and women) who are ≥ 18 years of age
diagnosed with primary unilateral non-metastatic or oligometastatic breast cancer
scheduled for surgery (mastectomy or breast conserving surgery; in combination with axillary lymph node dissection or sentinel node biopsy)
able to read, understand, and speak Dutch
distant metastases
planned bilateral lymph node surgery
oedema of the arm from another cause
an allergy to iodine or Indocyanine Green (ICG), or
Single group
Measurements for breast cancer related lymphedema (volumetric measurements, bioimpedance spectroscopy, bioimpedance analysis, tissue dielectric constant measurements, ultrasonography)
Other interventionAssessments related to different types of breast cancer related lymphedema at arm (1. self-reported swelling at arm, 2. subjective arm lymphedema, 3. objective arm lymphedema) using the Norman questionnaire, volume measurements (volumetry and perimetry), bioimpedance spectroscopy, and bioimpedance analysis Assessments related to different types of breast cancer related lymphedema at trunk/ breast (1. self-reported swelling at trunk/ breast, 2. subjective trunk/ breast lymphedema, 3. objective trunk/ breast lymphedema) using the Norman questionnaire, tissue dielectric measurements, and ultrasonography
Measurements for lymphatic problems (volumetric measurements, tissue dielectric measurement, lymphofluoroscopy)
Other interventionClinical assessments related to lymphatic problems (1. amount of swelling at arm by relative arm volume difference, 2. amount of swelling at trunk by percentage water ratio, 3. severity of dermal rerouting at upper limb and trunk by lymphofluoroscopy (i.e., near-infrared fluorescence imaging device)
Measurements for sensory processing problems by monofilaments, algometer, goniometer, and neurosensory analyzer
Other interventionClinical measurements related to nociceptive, neuropathic and central sensory problems based on the Quantitative Sensory Testing principles using different devices algometer, goniometer, standardized set of monofilaments, and neurosensory analyzer
Presence of subjective arm lymphedema
The presence of subjective arm lymphedema will be determined by the combination of two items. If self-reported swelling at arm is "yes" and objective arm BCRL is "no", then the presence of subjective arm BCRL will be defined as yes. To determine the presence of self-reported swelling at arm, we will use the Norman Questionnaire. If the patient responds ''yes'' to the item self-reported difference in the sizes of at least one of 3 sites (hand, lower arm, and upper arm), the presence of 'self-reported swelling at arm' is recorded as ''yes''. To determine the presence of objective lymphedema at arm, please see outcome 3. Unit of the outcome measure is yes/no. Assessment at pre-surgery (baseline) and 1 month, 6 months, and 12 months post-surgery
Presence of subjective trunk/ breast lymphedema
The presence of subjective trunk/ breast lymphedema will be determined by the combination of two items. If self-reported swelling at trunk/ breast is "yes" and objective trunk/ breast BCRL is "no", then the presence of subjective trunk/ breast BCRL will be defined as yes. To determine the presence of self-reported swelling at trunk/ breast, we will use the Norman Questionnaire. If the response is ''yes'' to the item self-reported difference in the sizes of at least one of these 2 sites (trunk or breast region), the presence of ''self-reported swelling in the trunk/breast'' is recorded as ''yes.'' Unit of the outcome measure is yes/no. Assessment at pre-surgery (baseline) and 1 month, 6 months, and 12 months post-surgery
Presence of objective arm lymphedema
4 methods are used to determine the presence of objective arm lymphedema: a) relative hand volume difference, b) relative arm volume difference, c) bioimpedance analysis, and d) bioimpedance spectroscopy at arm region If at least one of four cut-off values is present, the presence of objective arm lymphedema will be considered as yes: 1. an increase of relative hand volume difference between the affected and non-affected hands of ≥5% compared to the baseline difference OR 2. an increase of relative arm volume difference between the affected and non-affected arms of ≥5% compared to the baseline difference OR 3. Extra-cellular water ratio by Bioimpedance Analysis at affected arm of \>0.3850 OR 4. Extracellular water ratio by Bioimpedance Spectroscopy, \>6.5 change in the L-Dex score from the baseline score Unit of the outcome measure is yes/no. Assessment at pre-surgery (baseline) and 1 month, 6 months, and 12 months post-surgery
Presence of objective trunk/ breast lymphedema
2 methods are used to determine the presence of objective trunk/breast lymphedema: a) tissue dielectric measurement, b) skin thickness measurement at trunk/breast region If one of four criteria is present, the presence of objective trunk/ breast lymphedema will be considered as yes: 1. percentage of water content ratio at the trunk ≥ 1.32 OR 2. percentage of water content ratio at the trunk ≥ 1.40 OR 3. \> 2 standard deviations (SD) from the average skin thickness in at least one reference point on the trunk compared to the reference value at pre-surgery OR 4. \> 2 SD from the average skin thickness in at least one reference point one quadrant of the affected breast compared to the reference value at pre-surgery Unit of the outcome measure is yes/no. Assessment at pre-surgery (baseline) and 1 month, 6 months, and 12 months post-surgery
Amount of swelling at upper limb and trunk/breast
See outcomes 3 and 4 Presence of objective arm and trunk/ breast BCRL Total upper limb (hand + arm) volume is calculated by taking the sum of the hand volume and relative arm volume. Then, the difference between both upper limb is calculated. Relative upper limb volume difference is used for analysis. Average percentage water (PWC) value of reference points is calculated. PWC ratio=PWC affected side at post-surgery/PWC reference value at baseline is used for analysis. Assessment at pre-surgery, 1 month, 6 months, and 12 months post-surgery
Severity of dermal rerouting at upper limb and trunk/breast
Lymphofluoroscopy will be used. Indocyanine green (ICG)/ aqua is injected in the patient's hand; linear (normal) and dermal rerouting patterns are visualized after 90 minutes of the injection. The body is divided into 14 areas (11 areas at upper limb and 3 areas at trunk/breast). Each area is scored between 0 and 3: 0 (normal pattern), 1 (splash pattern), 2 (stardust pattern), and 3 (diffuse pattern). Total dermal rerouting score for arm is between 0 and 33. Total dermal rerouting score for trunk/ breast is between 0 and 9. Assessment at 1 month, 6 months, and 12 months post-surgery
Severity of myofascial adhesions at the level of the scars
The evaluation tool for Myofascial Adhesions in Patients after Breast Cancer (MAP-BC evaluation tool): assessed at 2 locations (i.e., axillary scar and breast or mastectomy scar). Each location is palpated for adhesions at 3 levels (i.e., skin, superficial, and deep) on a 4-points scale (0- no restriction, 1-limited restriction, 2-early and hard restriction, and 3-very stiff and tissue gliding is not possible). The total score of the MAP-BC is calculated by taking the sum of each item and is used for the analysis Total score ranges between 0 - 18. Assessment at 1 month, 6 months, and 12 months post-surgery
Severity of local muscle stiffness
Myofascial tissue stiffness will be evaluated at the affected and non-affected sides of the pectoralis major, infraspinatus, and teres major muscles. Average muscle stiffness score of 3 muscles at affected and non-affected side is calculated. Then, the local muscle stiffness ratio is calculated: Average muscle stiffness at the affected side in N/m/Average muscle stiffness at the non-affected side and this ratio is used for the analysis. Unit of the outcome measure is Newton/ meter. Assessment at pre-surgery (baseline) and 1 month, 6 months, and 12 months post-surgery
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Universitaire Ziekenhuizen KU Leuven
Lead sponsor
Universiteit Antwerpen
Collaborator
