Evaluation of the Validity of BIS as a Tool for Quantification of Lymphedema Through Comparison With Perometry and Self-Report
Conditions: Breast Cancer
Sponsor: Massachusetts General Hospital

 
 
 
 
STATUS PAGE 
PROTOCOL 11-325 
 
 
 
 
Closed To New Accrual 
 
 
Closure Effective Date: 08/06/2018 
Reason: Study Accrual Goal Met 
 
 
No new subjects may be enrolled in the study- as described above. 
Any questions regarding this closure should be directed to the study’s 
Principal Investigator 

DFCI Protocol No: 11-325
Front Sheet
05/10/2018 12:01 PM
Report Generated:
Evaluation of the validity of BIS as a tool for quantification of lymphedema through comparison with perometry and
self-report
Title:
Overall Principal Investigator
Email
Institution
Taghian, Alphonse G.
ataghian@partners.org
Massachusetts General Hospital
Overall Institution:
Massachusetts General Hospital
Primary Contact(s) for Questions
Email
Phone
Daniell, Kayla
kdaniell@mgh.harvard.edu
617-643-1306
Total Study-Wide Enrollment Goal:
270
Total DF/HCC Estimated Enrollment Goal:
270
Phase: III
Age:
Adults
Age Ranges:
Age-Adults (18-64); Age-Adults (65+)
Will all subjects be recruited from pediatric clinics?
CTEP Study:
No
Management Group(s):
Primary Management Group:
DF/HCC Breast Cancer
DF/HCC Breast Cancer
MGH Breast Cancer
MGH Regulatory Coordinators
Sponsor Name
Sponsor Protocol No
Roles
Grant Number(s)
DF/HCC Investigator
Regulatory
Dana-Farber/Harvard Cancer Center
Funding
Investigational Drug?
This study does not use a Drug/Biologic.
Investigational Device?
This study does not use an Investigational Device.
Risk Category:
Minimal Risk
Medical Record Review; Quality of Life; Questionnaires/Surveys/Interviews
Protocol Involves:
Date Range: (Medical Record Review and Specimen Collection studies)
IRB of Record:
Participating Sites under the DFCI IRB
Institution:
Massachusetts General Hospital
Participating Institutions Under Other IRB
None

Log Sheet  
Page 1 of 1 
 
Protocol Number: 11-325 
 
Approval Date:  
10/10/11 
(IRB meeting date when protocol/consent  
 approved or conditionally approved) 
 
Activation Date:  
12/28/11 
(Date when protocol open to patient entry) 
 
Approval signatures are on file in the Office for Human Research Studies, tel. 617-632-3029. 
 
 
 
 
Date 
Posted 
Revised Sections 
IRB Approval 
Date 
OHRS 
Version Date 
01/12/12 
Protocol replaced due to Amendment #1 
01/12/12 
- 
05/29/12 
Protocol and Front Sheet replaced due to Amendment 
#2 
05/25/12 
- 
07/23/12 
Consent Form replaced due to Amendment #3 
07/19/12 
07/20/12 
08/30/12 
Study Renewal/ Consent Form replaced due to 
Continuing Review #1 
08/22/12 
08/30/12 
08/01/13 
Protocol and Front Sheet replaced due to Amendment 
#4 
07/19/13 
n/a 
08/20/13 
Study Renewal/ Consent Form replaced due to 
Continuing Review #2 
07/23/13 
08/12/13 
07/22/14 
Study renewal/ Consent Form footer replaced due to 
Continuing Review #3 
06/25/14 
N/A 
06/23/15 
Study renewal/ Consent Form footer replaced due to 
Continuing Review #4 
06/09/15 
N/A 
Date 
Posted 
Revised Sections 
IRB Approval 
Date 
OnCore 
Version Date 
07/16/15 
Consent Form, Protocol and Front Sheet replaced due 
to Amendment #6 
06/30/15 
07/15/15 
09/14/15 
Consent Form, Protocol and Front Sheet replaced due 
to Amendment #7 
09/04/15 
09/10/15 
06/07/16 
Study renewal/ Consent Form footer replaced due to 
Continuing Review #5 
05/25/16 
06/07/16 
07/05/16 
Protocol and Consent Form replaced due to 
Amendment #8 
06/20/16 
07/01/16 
08/04/16 
Consent Form, Protocol and Front Sheet replaced due 
to Amendment #9 
08/04/16 
08/04/16 
Date 
Posted 
Revised Sections 
Approved 
Date  
Version Date 
(OnCore) 
03/23/17 
Consent Form and Front Sheet replaced due to 
Amendment #10 
03/20/2017 
03/21/17 
04/28/17 
Study renewal/ Consent Form footer replaced due to 
Continuing Review #6 
04/28/17 
04/28/17 
07/24/17 
Consent Form and Front Sheet replaced due to 
Amendment #11 
06/28/17 
06/28/17 
04/30/2018 
ON HOLD; All research must stop due to lapsed 
Continuing Review. Study approval expired 04/28/2018 
N/A 
N/A 
05/03/2018 
ON HOLD removed:  Study renewal/Consent Form 
footer replaced per Continuing Review #7 
05/03/2018 
05/03/2018 
05/10/2018 
Front Sheet replaced per Amendment #13 
05/08/2018 
N/A 
06/11/2018 
Consent Form, Protocol replaced per Amendment #12 
06/05/2018 
06/08/2018 
08/07/2018 
Study Closed – Study Accrual Goal Met 
08/06/2018 
n/a 
03/04/2019 
Study renewal/Consent Form footer replaced per 
Continuing Review #8 
03/04/2019 
03/04/2019 
 
 
 
 
 
 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
1
SECTION 1: Protocol Schema 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Presentation at Breast Center 
Diagnosis of breast cancer (FNA, core, incisional/excisional 
biopsy) 
Pre-Operative Assessment 
Each assessment will include: Perometer, BIS, and LEFT-
BC Questionnaire 
Post-Operative Assessment 
Continued Assessment 
Post-CT and/or XRT, then every 4-12 months for 24 
months following the completion of the patients’ breast 
cancer treatment (defined as last day of chemo or radiation 
therapy). Then the patient will be assessed at least once 
every 10 – 20 months per the patient’s oncology follow up 
assessments 
Register 
Definitive Breast Surgery  
Enrollment into 08-308 
Intervention Trial 
RVC ≥5% 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
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SECTION 2: BODY OF PROTOCOL 
 
TABLE OF CONTENTS 
1.0 INTRODUCTION 
1.1 Overview 
1.2 Background and Rationale 
1.2.1 Study Disease 
1.2.2 Previous Studies 
1.2.3 Literature Review 
1.2.4 Impact of Proposed Study 
2.0 OBJECTIVES 
2.1 Primary Objectives 
2.2 Secondary Objectives 
3.0 RESEARCH SUBJECT SELECTION 
3.1 Eligibility Criteria 
3.2 Exclusion Criteria 
3.3 Inclusion of Women, Minorities and Other Underrepresented Populations 
4.0 RESEARCH SUBJECT ENTRY 
4.1 Guidelines for DF/HCC and DF/PCC Institutions 
4.2 Registration Process for DF/HCC and DF/PCC Institutions 
5.0 STUDY DESIGN AND METHODS 
5.1 Design/ Study Type 
5.2 Selection of Instruments 
5.3 Description of Intervention 
5.4 Data Collection 
5.5 Description of Study Process 
5.5.1 Instrument Administration 
5.5.2 Intervention Administration 
5.5.3 Special Concerns 
5.5.4 Compensation 
5.6 Adverse Reactions and their Management 
5.6.1 Reporting Adverse or Unanticipated Events 
5.6.2 Anticipated Reactions 
5.6.3 Reaction management 
6.0 STATISTICAL ANALYSIS  
6.1 Primary and Secondary Endpoints 
6.2 Sample Size and Statistical Power 
6.3 Stratification Factors 
6.4 Stratification factors and their impact on design 
6.5 Early stopping rules, if appropriate 
6.6 Definition of and allowance in design for unevaluable / ineligible participants 
6.7 Analysis plan 
6.8 Handling of Missing Data  
7.0 REFERENCES 
8.0 APPENDICES 
 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
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1.0 INTRODUCTION 
 
1.1 Overview 
 
Prior studies of bioimpedance spectroscopy for the detection of lymphedema have 
left significant gaps in the literature regarding its use as a tool for the early detection of 
breast cancer-related lymphedema and its relationship with previously established 
measurement methods and self-reported symptoms.  The purpose of our study is to assess 
for lymphedema pre- and post- treatment (surgery, +/- radiation, +/- chemotherapy) 
through the concurrent use of perometry, bioimpedance spectroscopy, and self-report. 
From these assessments we will: 
 
1) Determine if BIS is a valid tool for early detection of lymphedema through 
comparison with the perometer and self-reported symptoms 
2) Evaluate the relationship between impedance ratios obtained through 
bioimpedance, volume changes measured by perometry and quantified using the 
relative volume change equation (RVC), and self-reported symptoms.  
 
From this data we will determine if bioimpedance spectroscopy is a valid tool for 
detecting and monitoring of early lymphedema. Furthermore we aim to determine the 
relationship between diagnostic indices utilized by perometry and BIS such that 
measurements with BIS can be related to the previously established definitions of 
lymphedema and used in a clinically meaningful way.  
 
1.2 Background and Rationale 
 
1.2.1 Study Disease 
Lymphedema is an abnormal collection of protein-rich fluid that rests in the 
interstitial tissues (1). The development of upper extremity lymphedema following 
treatment for breast cancer is well documented (2-6). The impact of lymphedema on 
quality of life is supported by research and clinical experience in treating patients with 
this distressing condition that is often a constant reminder of their cancer treatment (7). 
Symptoms of pain, stiffness and loss of function typically accompany the onset of 
lymphedema, and have been found to compound changes in quality of life (8-11).  
Despite its known impact on patients and prevalence in the literature, reported 
rates of lymphedema vary significantly (12,13). While it has been reported that 
lymphedema occurs in at least 25% of patients who have had surgery and radiation 
treatment for breast cancer (14-16), others report rates as high as 50% (17). The wide 
range in lymphedema incidence rates can be attributed to the lack of a standard method of 
measurement or index for diagnosis of lymphedema, which may lead to misdiagnosis or 
delay in treatment (18,19). In light of recent evidence which demonstrates the importance 
of early detection for successful management of lymphedema, it is important to 
determine the relationship among measurement techniques and diagnostic indices to 
establish a universal method of measurement and definition for lymphedema (20).  
Previously, lymphedema resulting from breast cancer treatment has been assessed 
as using limb circumference or volume to estimate the excess size of the affected limb as 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
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compared to the unaffected limb (21). Circumferential measurements are obtained using 
tape measurements at various point(s) along the limb, from which volume is calculated 
using the truncated cone method. Limb volume may be directly measured with 
optoelectric perometry or water displacement (volumetry). Common criteria for diagnosis 
of lymphedema include >2cm circumference difference,  >200 ml volume difference, or 
10% limb volume change between arms or between the same arm before and after 
surgery, as well as self-report of symptoms(12). 
More recently, bioelectrical impedance analysis (BIA) has also been utilized for 
the detection of breast cancer-related lymphedema. BIA measures the opposition to flow 
of an electric current passed through the body at single or multiple frequencies, and 
resistance to the flow of this current is reported as an impedance value. The level of 
impedance to a current depends upon the capacitive and inductive properties of the 
medium through which the current is passed (22). Single-frequency bioimpedance 
analysis (SF-BIA) devices pass an electrical current through the body at only one 
frequency (23), whereas multiple frequency bioimpedance analysis (MF-BIA) and 
bioimpedance spectroscopy (BIS) utilize multiple frequencies and can detect fluid 
volume changes specifically related to extracellular fluid (22). Increased fluid in the 
extracellular space of the limb, as occurs in lymphedema, decreases resistance to current 
flow and results in a lower impedance value (24,25). It has been established that 
increased limb volume based upon circumferential measurements correlates with a 
decreased impedance value obtained via BIA (24).  
To quantify lymphedema using bioimpedance analysis, the ratio of impedance 
values of the affected to unaffected limb is calculated. The difference between the 
measured impedance ratio and an established normal range is then assessed as standard 
deviations from the norm, and 3+ deviations is considered to be indicative of 
lymphedema (23). Since there is no direct mathematical relationship between impedance 
(in ohms) and volume (in ml) of the limb, it is not possible to directly compare 
impedance values obtained using BIA with limb volume changes obtained from 
circumferential or volumetric measurements (24).  
 
1.2.2 Previous Studies 
 
Within the MGH-Gillette Breast Center, lymphedema screening has been 
provided to all patients prospectively through Perometric arm volume measurements 
during and after treatment. Since July 2005, over 2200 patients have undergone a pre-
operative baseline measurement, and 1123 patients have two additional measurements 
thereafter with a median follow-up of 22.4 months after surgery. Through the 
development of this screening program, continuous research and analysis of interim data 
has been completed under Partners Protocols 2005P-001038 and 1999P-009256. As part 
of this evaluation, the Lymphedema Studies Team has developed an equation for Relative 
Volume Change (RVC), which quantifies the percent of change in arm volume on the 
affected/treated side as compared to the initial pre-operative measurements (26).  
To further understand the detrimental effect that fear of lymphedema development 
as well as the presentation of this complication may have on a patient, our team has 
developed a longitudinal screening and questionnaire protocol (Partners Protocol 
#2008P-000540). Under this protocol, women who complete a preoperative perometer 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
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measurement will, in addition to periodic measurements, complete the Lymphedema 
Evaluation Following Treatment for Breast Cancer Questionnaire (LEFT-BC) which will 
allow for the evaluation of changes in functionality, upper extremity utilization (fear 
associated avoidance), and quality of life. Screening visits (involving both a perometer 
measurement and completion of the LEFT-BC) occur pre-operatively, at the initiation 
and conclusion of each type of treatment (surgery, chemotherapy and radiation), and 
every 4-7 months following the completion of treatment. 
 
Additionally, in order to evaluate the efficacy of early intervention for mild and 
moderate edema, our team developed DFHCC Protocol #2008P-000308, in which a 
sample of women who experience mild and moderate volume changes are randomized to 
postoperative compression. If during the course of a patient’s screening visits as part of 
Protocol 2008P-000540 they are found to have an RVC of ≥ 5%, which remains above 
5% at a verification measurement within 4-8 weeks, the patient may enroll in the 
intervention arm of the study. Dependent upon their RVC, these patients are randomized 
either within Group I –Mild Lymphedema (5-<10% RVC) or Group II – Moderate 
Lymphedema (≥10-20% RVC). Patients with mild lymphedema are randomized either to 
observation or compression, and those with moderate lymphedema are randomized either 
to compression or compression with night compression bandaging.  
In the proposed study, we aim to prospectively screen a cohort of patients with 
bioimpedance spectroscopy, in addition to the perometer and LEFT-BC questionnaire to 
determine if BIS is a valid clinical tool for assessing lymphedema in breast cancer 
patients. Through the collection of concurrent longitudinal measurements with the 
perometer and BIS, we will establish the relationship between these assessment methods, 
as well as evaluate the symptoms, functional disability, and changes in quality of life that 
accompany these measurements.  This study will be and all previous studies were 
supported by 2 NIH grants totally >$2.2M / 5 years [Award Number R01CA139118 (PI: 
Dr. Taghian), Award Number P50CA089393 (PI: Dr. Taghian)]. 
 
 
1.2.3 Literature Review 
 
The earliest publication describing BIS occurred in 1992, in which Ward et al 
described the results of assessment for lymphedema using bioimpedance and limb 
volume calculated from circumferences in a cohort of women with and without clinical 
lymphedema (24).  Their data showed that impedance values did not entirely discriminate 
between women with lymphedema and control subjects. In a subsequent study (1996) 
assessing the utility of BIA devices in comparison with circumferential measurements, 
Cornish et al demonstrated a 3 to 4-fold increased sensitivity of BIA compared to 
circumferential measurements (27). In 2001, a large prospective trial assessing breast 
cancer patients with BIA and circumferential measurements confirmed the suitability of 
BIA as a reliable diagnostic procedure for early detection of lymphedema, and sensitivity 
of BIA and circumferences for early detection were shown to be 100% and 5%, 
respectively (23). A study by Hayes comparing circumferences and BIA reported 
sensitivities of 35% and 65%, respectively, for detection of lymphedema in an analysis of 
176 breast cancer patients 6 months post-surgery (28).  

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
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Several studies have also assessed the utility of BIA as compared to 
optoelectronic perometry in the detection of lymphedema. In 2009, Ward showed that 
impedance ratios were highly correlated with limb volume ratios measured using 
perometry in an analysis of 45 breast cancer patients with clinical lymphedema and 21 
women without lymphedema (29). In a comparison of physical measurement methods 
and self-report in a small cohort of patients post-breast cancer treatment (n=10), Jain et al 
also showed a high concordance among measurements with BIA and perometry, as well 
as a moderate correlation of these methods with self-report (22).  
An examination of the relationship among several methods of lymphedema 
detection including BIS, perometry, circumferences, and self-report has demonstrated a 
strong concordance among these techniques.  In a comparison of these methods in a 
cohort of women with and without clinically diagnosed lymphedema, Czernic (25) and 
Ridner (30) and found statistical agreement among methods in the detection of clinical 
lymphedema (n= 25, n= 51, respectively).  
 
1.2.4 Impact of Proposed Study  
 
As one of the most recent devices to be applied in the assessment of breast 
cancer-related lymphedema, it is important to validate BIS as an effective tool for early 
detection of lymphedema and to establish the relationship of its index with traditional 
volume-based measurement techniques. This study would be significant because it would 
prospectively screen a large cohort of women for development of early lymphedema with 
the concurrent use of several assessment methods including BIS, perometry, and self-
reported symptoms via the LEFT-BC Questionnaire. Though a concordance among BIA 
and perometry for detection of clinically diagnosed lymphedema has been established, 
previous studies use small sample sizes, lack pre-surgical assessment and adequate 
follow-up, and do not define or evaluate the criteria for classification of lymphedema 
based upon assessment methods. If bioimpedance is to be applied for early detection of 
lymphedema in the clinical setting, it is important to determine how the diagnostic scale 
utilized by BIA correlates with traditionally established definitions of lymphedema. The 
concurrent and regular assessment of at-risk women using BIS, perometry, and self-
report will allow for analysis of the utility of BIS as well as the correlation among 
definitions of lymphedema corresponding with each assessment technique.  
 
2.0 OBJECTIVES 
 
2.1 Primary Objectives: 
-To assess the validity of BIS as a tool for quantification of lymphedema through 
comparison with perometry 
-To determine relationship between impedance ratios, relative volume changes 
(RVC), and self-reported symptoms 
 
2.2 Secondary Objectives:  
-Compare diagnostic criteria for lymphedema correlating with each assessment 
method 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
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-Define the natural history of lymphedema and determine a threshold for 
intervention using BIS  
 
3.0 RESEARCH SUBJECT SELECTION 
 
Eligibility and exclusion criteria are similar to those for Partners Protocol 2008P-000540 
and DFHCC Protocol #2008P-000308. 
 
3.1 Eligibility Criteria 
 
Participants must meet the following criteria on screening examination to be eligible to 
participate in the study: 
3.1.1 Participants must have histologically or cytologically confirmed invasive or 
in-situ carcinoma of the breast. 
3.1.2 Participants must have undergone sentinel node mapping or axillary 
dissection. 
3.1.3 Age >18 years. 
3.1.4 Life expectancy of greater than 1 year. 
3.1.5 Ability to understand and the willingness to sign a written informed consent 
document. 
3.1.6 Willingness to comply with required follow up perometer and BIS 
measurements and completion of LEFT-BC questionnaire. 
3.1.7 Participant must be either English or Spanish speaking 
 
3.2 Exclusion Criteria 
 
Participants who exhibit any of the following conditions at screening will not be eligible 
for admission into the study: 
3.2.1 Patients who have known metastatic disease or other locally advanced 
disease in the thoracic or cervical regions. 
3.2.2 Any patient who will not be returning routinely for follow-up at MGH or 
DFHCC. 
3.2.3 Participants with known brain metastases will be excluded from this clinical 
trial because of their poor prognosis and because they often develop progressive 
neurologic dysfunction that would confound the evaluation of neurologic and 
other adverse events. 
3.2.4 History of primary lymphedema. 
3.2.5 History of prior surgery or radiation to the head, neck, upper limb, or trunk. 
3.2.6 Participants who have evidence that axillary lymph node malignancy is 
causing lymphedema due to recurrence as per physician discretion. 
3.2.7 Any patient who has bilateral lymph node mapping or dissection.  
3.2.8 Any patient with a current case of cellulitis. 
3.2.9 Patients with a history of a different malignancy are ineligible except for the 
following circumstances. Individuals with a history of other malignancies are 
eligible if they have been disease-free for at least 5 years and are deemed by the 
investigator to be at low risk for recurrence of that malignancy. Individuals with 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
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the following cancers are eligible if diagnosed and treated within the past 5 years: 
cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. 
 
3.3 Inclusion of Women, Minorities and Other Underrepresented Populations 
 
No exclusions will be made on the basis of race or ethnicity. Efforts will be made by the 
Lymphedema Clinical Research Staff to enroll all eligible participants and special effort 
will be given to the enrollment of minorities.  
 
4.0 RESEARCH SUBJECT ENTRY 
 
The Clinical Research Coordinators will be responsible for consenting the subjects at the 
time of the pre-operative assessment with Perometry, BIS, and the LEFT-BC 
Questionnaire. All clinical research staff will be trained to utilize both devices and to 
administer the questionnaire.   
 
4.1 General Guidelines for DF/HCC and DF/PCC Institutions 
 
Institutions will register eligible participants with the DF/HCC Quality Assurance Office 
for Clinical Trials (QACT) central registration system. Registration must occur prior to 
initiation of study processes or completion of study materials by participants. 
 
A member of the study team will confirm eligibility criteria and complete the protocol-
specific eligibility checklist. 
 
Following registration, participants may begin protocol processes. If a participant does 
not complete study processes and/or materials following registration, the participant’s 
protocol status must be changed. Notify the QACT Registrar of participant status changes 
as soon as possible. 
 
4.2 Registration Process for DF/HCC and DF/PCC Institutions 
 
The QACT registration staff is accessible on Monday through Friday, from 8:00 AM to 
5:00 PM Eastern Standard Time. If a participant must be registered during off-hours or 
holidays, call the QACT registration line at 617-632-3761 and follow the instructions for 
registering participants after hours. 
 
The registration procedures are as follows: 
1. Obtain written informed consent from the participant prior to the performance of any 
study related procedures or assessments. 
2. Complete the protocol-specific eligibility checklist using the eligibility assessment 
documented in the participant’s medical/research record. To be eligible for registration 
to the study, the participant must meet each inclusion and exclusion criteria listed 
on the eligibility checklist. 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
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Reminder: Confirm eligibility for ancillary studies at the same time as eligibility for the 
treatment study. Registration to both treatment and ancillary studies will not be 
completed if eligibility requirements are not met for all studies. 
3. Fax the eligibility checklist(s) and all pages of the consent form(s) to the QACT at 
617-632-2295. 
4. The QACT Registrar will (a) validate eligibility, (b) register the participant on the 
study, and (c) randomize the participant when applicable. 
5. The QACT Registrar will send an email confirmation of the registration and/or 
randomization to the person initiating the registration immediately following the 
registration and/or randomization. 
 
5.0 STUDY DESIGN AND METHODS 
 
5.1 Design / Study Type 
 
This will be a prospective trial to assess arm edema using Bioiompedance Spectroscopy 
(BIS), perometry, and a comprehensive self-report questionnaire (LEFT-BC) in a cohort 
of patients who have had sentinel lymph node mapping or axillary dissection as part of 
breast cancer surgery. All patients will have their first baseline assessment after diagnosis 
for breast cancer (core biopsy, FNA or incisional/ excisional biopsy) and before their 
definitive breast surgery. Patients will be assessed for lymphedema at the initiation and 
completion of each treatment process, and every 4-12 months throughout follow-up 
during the first 24 months following completion of their breast cancer treatment. 
Subsequently they will be assessed at least once every 10-20 months following this 24 
month post treatment time period. This research will be done for 5 years throughout the 
patient’s follow-up for breast cancer, or as long as the patient returns to MGH for care 
related to breast cancer. This trial aims to accrue a total of 200 patients in 5 years. 
 
5.2 Selection of Instruments 
 
Bioimpedance Spectroscopy (BIS) 
 
BIS has been proposed to be the new standard for early detection of lymphedema 
in breast cancer patients through quantification of extracellular fluid content of the arm 
(19). It is purported to be highly specific, accurate, sensitive, and have a high inter-rater 
reliability and repeatability within and between testing centers (19). The L-Dex U400 is 
the BIS device to be used in this protocol, and received U.S. FDA clearance in 2008 for 
aiding in the clinical assessment of unilateral lymphedema of the arm in breast cancer 
patients (31).  
 
Assessment with the BIS device will be conducted by a Lymphedema Studies 
Clinical Research Staff member. Electrodes will be placed in specifically designated 
locations while the patient maintains a supine position. According to manufacturers, the 
actual amount of electrical current passed through the body is imperceptible to most 
patients, is applied non-invasively and is applied over a brief period (less than 1 second) 
(31). Measurements will be taken pre- and post-operatively, as well as at screening visits 
per study design, and each measurement takes about 2-3 min. including electrode 
placement.  

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
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 Perometer 
The perometer is a well-validated instrument for quantifying volume in a limb, 
and has been a regular part of the standard of care for MGH breast cancer patients since 
2005. Patients are routinely measured (1) at diagnosis, (2) after surgery, (3) after 
chemotherapy, (4) after radiation, (5) at four to seven month follow-up visits that 
continue for five years, and (6) any time a patient reports with new symptoms of swelling 
or arm discomfort outside these time frames. The perometer provides highly reliable and 
valid arm volume measurements, with no physical discomfort or inconvenience to the 
patient. It utilizes infrared lamp-light receiver pairs contained within a frame which is 
moved along the extremity. As indicated by our preliminary analyses and the literature, 
the perometer calculates volume within 1% accuracy (33). This calculation of volume is 
accurate within a standard deviation of 8.9 ml and a .55% difference with repeated 
measurements (33). The perometer can give detailed information about arm volume in 
milliliters, the percent difference between the volumes of both arms, the location of the 
swelling in the arm as well as a follow-up clearly showing progression of the 
lymphedema over time.  
Measurements of arm volume with the perometer will be taken pre- and post-
operatively, as well as at screening visits per study design. All arm volume measurements 
will be converted to a percent RVC. The RVC calculation will indicate volume changes 
in the affected arm as compared to the baseline measurement. This value will indicate 
whether or not a patient is experiencing lymphedema for the purposes of this study and 
will determine patient eligibility for enrollment into Partners Protocol 08-308.  
Questionnaire  
The primary source of data on symptoms, functionality, arm use and quality of 
life will be derived from a questionnaire completed at each lymphedema assessment. 
Patients who are enrolled in the study will complete the questionnaire at their initial point 
of enrollment (after diagnosis and prior to definitive breast surgery), and at all subsequent 
assessments.  
 
This questionnaire is currently being utilized as part of Partners’ Protocols 08-540 
and DFHCC Protocol #08-308 and as such has been completed by over 500 patients on 
protocol since 2009. It was developed to analyze symptoms, functionality, fear avoidance 
behavior, and quality of life. This questionnaire is referred to as the Lymphedema 
Evaluation Following Treatment for Breast Cancer Questionnaire (LEFT-BC), and it has 
been pilot tested for clarity, readability, and validity. This pilot testing was completed 
with a sample of 20 patients currently undergoing perometer measurements as a standard 
of care within the MGH Gillette Breast Center. After completion of the pilot, adjustments 
were made to the questionnaire to increase clarity and readability. The complete 
questionnaire is included in Appendix 2. 
In order to minimize respondent burden the questionnaire was limited to 6 written 
pages and took between 5-12 minutes to complete during the pilot study. We will utilize 
tablet style PCs for questionnaire completion within the clinic. Dr. Kevin Hughes and 
Brian Drohan, MS developed the LEFT-BC Questionnaire program by formatting the 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
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questionnaires for the tablet PCs, and a corresponding database for data logging. The 
questionnaires will be completed by patients in a point and click manner. In the event that 
tablet PCs are not available, paper copies of the questionnaire will be available for 
participant visits. Questionnaire responses from paper based questionnaires will be 
manually entered into the database. 
 
Risk Assessment  
 
At each lymphedema assessment, patients will be verbally asked a short series of 
questions to provide further information for an analysis of the risk factors involved in the 
development of lymphedema (see Appendix 3). These questions include: number of 
blood draws, blood pressures, or injections on the affected arm since the last lymphedema 
assessment. Also recorded is the number of flights, total hours in flight, and whether a 
sleeve was worn while flying since the last lymphedema assessment.  
 
5.3 Description of Intervention  
 
Results of assessment with BIS will be blinded such that only a ≥5% RVC 
measured using the perometer will be considered indicative of lymphedema. If at any 
time while enrolled in this study a patient is detected to have an RVC≥ 5% by perometry, 
a verification measurement including assessment with perometry, BIS, and the LEFT-BC 
questionnaire will be conducted at a 4-8 week interval. If at this time the patient’s RVC 
measured by perometry is confirmed above 5%, the patient will be offered enrollment 
into the DFHCC 08-308 Intervention Protocol and/or referred to a clinician for 
appropriate care. Patients that enroll into Protocol #08-308 will continue to be measured 
using BIS at the time of each assessment as required by the protocol. Patients that refuse 
enrollment into the intervention protocol will remain in the current study.  
 
 
5.4 Data Collection   
 
Patients will be assessed pre-operatively, at the initiation and conclusion of each 
type of treatment (surgery, chemotherapy and radiation), and every 4-12 months 
following the completion of treatment for a period of 24 months. Subsequently they will 
be assessed at the time their follow-up appointments with their oncologists, with no more 
than 20 months between measurements. At the time of each assessment, the patient will 
be measured with the perometer, bioimpedance spectroscopy, and will complete the 
LEFT-BC questionnaire.  Data collected at each visit includes arm volume measurements 
obtained via perometry and quantified using the RVC equation, bioimpedance ratios 
collected via BIS, self-reported symptoms obtained via the LEFT-BC questionnaire.  
 
5.5 Description of Study Process 
 
The proposed study will incorporate the use of bioimpedance spectroscopy (BIS) 
to evaluate its validity for detecting and monitoring lymphedema. Patients will be 
assessed for lymphedema in a prospective manner using perometry, BIS, and the LEFT-
BC questionnaire, accruing a total of 200 patients in 5 years. The entire study will be 

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Version Date: 4/18/2018 
 
 
 
12
completed at the MGH main campus, and all patients who present for a baseline (pre-
operative) arm measurement and meet the eligibility criteria will be offered the 
opportunity to participate in this trial. At this time the purpose of the trial will be 
explained, and any patient that wishes to participate will be assessed using the perometer, 
BIS, and provided with the LEFT-BC questionnaire to complete prior to surgery. Patients 
who do not wish to participate in the proposed trial will be asked to participate instead in 
Partners Protocol #2008P-000540, which involves regular assessment with the perometer 
and completion of the LEFT-BC questionnaire at the time of each perometer 
measurement.  
 
5.5.1 Instrument Administration  
The perometer, bioimpedance spectroscopy (BIS) device, and the LEFT-BC 
questionnaire will all be administered by a Lymphedema Studies Clinical Research Staff. 
Patients will be notified upon arrival to the clinic that they will undergo a lymphedema 
assessment on that date using the perometer, BIS, and LEFT-BC questionnaire. 
Perometry measurements will be conducted in a room specifically allocated for its use, 
and require about 5-10 minutes for completion. BIS assessments will be conducted in a 
clinical room and require 2-3 minutes to complete. The LEFT-BC questionnaire will be 
administered on a tablet PC in a clinical room or given as a paper copy for the patient to 
complete in the event that tablet PC’s are not available. The questionnaire takes 5-12 
minutes to complete.  
 
5.5.2 Intervention Administration  
As stated previously, results of assessment with BIS will be blinded. Patients that 
experience a ≥5% RVC determined by measurement with perometry and maintain a ≥5% 
RVC at the 4-8 week verification measurement will be eligible for enrollment into 
DFHCC Protocol #08-308 Intervention Trial. These patients will continue to be measured 
using BIS at the time of each assessment as required by the protocol, and intervention 
will be administered as dictated by DFHCC Protocol #08-308. Patients that refuse 
enrollment into the intervention protocol will be referred to a clinician for appropriate 
care and will remain on the current study.  
 
 
5.5.3 Special Concerns 
 
Please see sections 5.6.2 and 5.6.3 for anticipated reactions and resolution 
strategies.  
 
 
5.5.4 Compensation 
No compensation is considered. 
 
 
 
5.60 
 Adverse Reactions and their Management 
 
5.6.1 Reporting Adverse or Unanticipated Events 
 
Adverse event collection and reporting is a routine part of every clinical trial. This study 
will use the descriptions and grading scales found in the NCI Common Terminology 

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Version Date: 4/18/2018 
 
 
 
13
Criteria for Adverse Events version 3.0 (CTCAE v3.0) that is available at 
http://ctep.cancer.gov/reporting//ctc.html. 
 
Information on all adverse events, whether reported by the participant, directly observed, 
or detected by physical examination, laboratory test or other means, will be collected, 
recorded, followed and reported as described in the following sections. 
 
Adverse events experienced by participants will be collected and reported from 
initiation of treatment, throughout the study, and within 30 days of the last follow-
up visit. Participants who experience an ongoing adverse event or related to a 
study procedure beyond 30 days will continue to be contacted by a member of the 
study team until the event is resolved, stabilized, or determined to be irreversible 
by the participating investigator. Participants should be instructed to report any 
serious post-study event(s) that might reasonably be related to participation in this 
study. The investigator should notify the IRB and any other applicable regulatory 
agency of any unanticipated death or adverse event occurring after a participant 
has discontinued or terminated study participation that may reasonably be related 
to the study. 
• Adverse Event (AE) 
 
An adverse event (AE) is any undesirable sign, symptom or medical 
condition or experience that develops or worsens in severity after starting 
the first dose of study treatment or any procedure specified in the protocol. 
For the purpose of this study we will be defining adverse events as any of the 
following that pertain to the patient’s breast cancer-related lymphedema: 
 
o Psychological distress caused by heightened awareness of 
lymphedema and the potential of developing the condition 
 
 
• Serious adverse event (SAE) 
 
A serious adverse event (SAE) is any adverse event, occurring at any dose 
and regardless of causality that:  
• Results in death 
• Is life-threatening. Life-threatening means that the person was at 
immediate risk of death from the reaction as it occurred, i.e., it 
does not include a reaction which hypothetically might have 
caused death had it occurred in a more sever form. 
• Requires or prolongs inpatient hospitalization  
• Results in persistent or significant disability/incapacity.  
• Is a congenital anomaly or birth defect; or 
jeopardizes the participant and require medical or surgical intervention 
to prevent one of the outcomes listed above.  

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Version Date: 4/18/2018 
 
 
 
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Events not considered to be serious adverse events are hospitalizations 
for: 
• routine treatment or monitoring of the studied indication, not 
associated with any deterioration in condition, or for elective 
procedures 
• elective or pre-planned treatment for a pre-existing condition 
that did not worsen 
• emergency outpatient treatment for an event not fulfilling the 
serious criteria outlined above and not resulting in inpatient 
admission 
• respite care 
 
• Expectedness 
 
Adverse events can be 'Expected' or 'Unexpected.'  
o Expected adverse event 
 
Expected adverse events are those that have been previously 
identified as resulting from administration of the agent. For the 
purposes of this study, an adverse event is considered expected 
when it appears in the current adverse event list, the 
Investigator’s Brochure, the package insert or is included in the 
informed consent document as a potential risk.   
 
Refer to Section 6.1 for a listing of expected adverse events 
associated with the study agent(s). 
o Unexpected adverse event 
 
 
For the purposes of this study, an adverse event is considered 
unexpected when it varies in nature, intensity or frequency from 
information provided in the current adverse event list, the 
Investigator’s Brochure, the package insert or when it is not 
included in the informed consent document as a potential risk.   
• Attribution 
 
Attribution is the relationship between an adverse event or serious adverse 
event and the study treatment. Attribution will be assigned as follows: 
 
• Definite – The AE is clearly related to the study treatment. 
• Probable – The AE is likely related to the study treatment. 
• Possible – The AE may be related to the study treatment.  
• Unlikely - The AE is doubtfully related to the study treatment. 

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Version Date: 4/18/2018 
 
 
 
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• Unrelated - The AE is clearly NOT related to the study treatment. 
5.6.1.1 Procedures for AE and SAE Recording and Reporting 
 
Reporting participating investigators will assess the occurrence of AEs and 
SAEs at all participant evaluation time points during the study.  
 
All AEs and SAEs whether reported by the participant, discovered during 
questioning, directly observed, or detected by physical examination, laboratory 
test or other means, will be recorded in the participant’s medical record and on 
the appropriate study-specific case report forms.  
 
The descriptions and grading scales found in the CTEP Active Version of the 
NCI Common Terminology Criteria for Adverse Events (CTCAE) will be 
utilized for AE reporting. The CTEP Active Version of the CTCAE is identified 
and located on the CTEP website at: 
 
 http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.  
 
All appropriate treatment areas should have access to a copy of the CTEP 
Active Version of CTCAE. 
5.6.1.2 Reporting Requirements 
 
Each investigative site will be responsible to report SAEs that occur at that 
institution to their respective IRB. It is the responsibility of each participating 
investigator to report serious adverse events to the study sponsor and/or others 
as described below.  
5.6.1.3 Reporting to the Study Sponsor 
N/A. Single site study. 
5.6.1.4 Serious Adverse Event Reporting 
 
All serious adverse events that occur after the initial dose of study treatment, 
during treatment, or within 30 days of the last dose of treatment must be reported 
to the DF/HCC Overall Principal Investigator on the local institutional SAE form. 
This includes events meeting the criteria outlined in Section 11.1.2, as well as the 
following: 
 
• Grade 2 (moderate) and Grade 3 (severe) events that are 
unexpected and at least possibly related/associated with the 
intervention. 
 

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Version Date: 4/18/2018 
 
 
 
16
• All Grade 4 (life-threatening or disabling) events that are 
unexpected or not specifically listed in the protocol as not 
requiring reporting. 
 
• All Grade 5 (fatal) events while the participant is enrolled and 
actively participating in the trial OR when the event occurs within 
30 days of the last study intervention.  
 
Note: If the participant is in long term follow up, report the death at 
the time of continuing review.  
5.6.1.5 Non-Serious Adverse Event Reporting  
 
Non-serious adverse events will be reported to the DF/HCC Overall 
Principal Investigator on the toxicity Case Report Forms.   
5.6.1.6 Reporting to the Institutional Review Board (IRB) 
 
Each adverse event will be assessed to determine if it meets the criteria for serious 
adverse event. If a serious adverse event occurs, expedited reporting will follow 
local policies, and federal guidelines and regulations as appropriate. It is the 
responsibility of the participating investigator to notify the Principal Investigator (or 
Protocol Chair), IRB, and others of all serious adverse events as required in the 
protocol. The Principal Investigator (or Protocol Chair) will provide information 
with respect to adverse events and safe use of the study treatment (e.g., safety 
reports, Action Letters) to all participating investigators as soon as the information 
becomes available. Investigative sites within DF/HCC will report all serious adverse 
events directly to the DFCI Office for Human Research Studies (OHRS). 
 
5.6.2 Anticipated Reactions 
 
Since completion of the LEFT-BC questionnaire is voluntary, it is foreseeable that the 
use of the questionnaires may heighten the awareness of lymphedema and possible 
symptoms.  
 
Additionally, assessment with BIS is voluntary and may increase awareness of 
lymphedema and cause distress regarding the potential development of the condition. 
Use of the device is considered safe and has regulatory clearance in the United States 
to “support the measurement of extracelluar fluid volume differences between the 
arms to aid in the clinical assessment of unilateral lymphedema of the arm in women” 
(31).  According to manufacturers, “the actual amount of electrical current passed 
through the body is imperceptible to most patients, is applied non-invasively and is 
applied over a brief period (less than 1 second)” (31).  
 
5.6.3 Reaction Management  
 

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Version Date: 4/18/2018 
 
 
 
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In the event that a participant does feel an increased level of distress or discomfort, the 
social work team within the breast cancer center have confirmed their willingness and 
ability to provide additional counseling if necessary. Julie Berrett, MSW has confirmed 
that she will be available to any patients who experience such adverse effects. 
 
 
 
 
 
Julie Berrett, LICSW  
 
 
 
 
P. (617) 643-2355 
 
 
 
 
JBERRETT@PARTNERS.ORG 
 
6.0 STATISTICAL ANALYSIS  
 
6.1 Primary and Secondary Endpoints 
 
The primary aims of the study are to assess the validity of BIS measurements by 
comparison with perometery and determine the relationships of BIS measurements to 
perometer measurements and to self-reported symptoms. The secondary aims will be to 
compare diagnostic criteria for lymphedema for each assessment method, assess the 
natural history of lymphedema using BIS, and determine a threshold for intervention 
using BIS.  Thus primary endpoints will subsist in volumetric and BIS measurements of 
each arm at the baseline examination and during follow-up visits, as well as data captured 
by LEFT-BC questionnaires. The changes of arm volumes will be quantified using 
established RVC formula (26), and we will use a similar formula for quantification of 
BIS changes after evaluating the statistical distribution of BIS measurements. 
 
6.2 Sample Size and Statistical Power 
 
The sample size will be determined with the prospect of primary aim of this 
study, i.e, to evaluate the correlation between arm volume changes measured by 
perometry and quantified using RVC formula (26) and using relative changes of 
impedance measured by biompedance spectroscopy (BIS). We want to evaluate this 
correlation for all subjects enrolled, and separately, for a subgroup of those subjects who 
develop lymphedema with RVC≥5%. The first analysis will evaluate overall agreement 
between these two techniques and the second analysis will evaluate agreement between 
assessment of lymphedema grade by both techniques. We plan to quantify the 
relationship between these two measurement methods using Kendall's tau coefficient 
(34).  
We chose to use a non-parametric correlation coefficient to account for a possible 
non-linear form of the relationship between the two measurements, and for a possible 
non-normal distribution of BIS measurements. We expect a moderately high correlation 
between these measurements, tau=0.50 . The choice of sample size is motivated by a 
need to evaluate the correlation with sufficient precision rather than by a hypothesis test: 
we want to obtain a lower bound of 95% confidence interval for the estimate of tau of no 
less than 0.2 in the LE group and of no less than 0.42 overall. We assume that 10% of 
enrolled subjects will develop lymphedema with RVC≥5%.  Furthermore, we expect that 
up to 20% of paired measurements may be missing due to non-compliance or technical 
problems.   

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Version Date: 4/18/2018 
 
 
 
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Sample size calculations are based on approximate confidence intervals for 
Kendall's tau (35). The minimum number of measurements, to attain the required 
precision in the LE group is n=16; however, accounting for missing data we need to 
enroll 20 patients with LE and 200 patients overall. We thus expect to have 160 non-
missing pairs of measurements overall, this allows us to determine Kendall's tau with 
95% confidence interval from 0.426 to 0.567. 
 
Of note, patients that are enrolled pre-operatively and subsequently undergo 
bilateral breast surgery, rendering them ineligible for the study, will not be counted 
towards the overall accrual goal of 200 subjects.  
 
6.3 Stratification Factors 
 
N/A: this is not a randomized study. 
 
6.4 Stratification factors and their impact on design 
 
The analysis will be stratified on the time of follow-up, volumetric and BIS 
changes, as well as self-reported symptoms will be correlated at the corresponding time 
points.  
 
6.5 Early stopping rules, if appropriate 
 
N/A: the study will not have early stopping rules. 
 
6.6 Definition of and allowance in design for unevaluable / ineligible participants 
 
Only eligible patients, as specified by inclusion and exclusion criteria, will 
participate in this study. In the event that a participant is found to be ineligible according 
to the exclusion criteria after enrollment into the study, the patient will be removed and 
the QACT will be notified. All data corresponding to these patients will be excluded in 
the analyses. If a participant becomes ineligible according to the exclusion criteria while 
actively enrolled in this study, the participant will be removed and the QACT will be 
notified. Any data corresponding to these patients collected  prior to removal will be 
included in the analyses.  The sample size for this study takes into account potential 
unevaluable/ ineligible participants by aiming to accrue 200 participants, when only 160 
non-missing pairs of measurements overall are needed to meet the desired confidence 
interval for statistical analysis.  
 
6.7 Analysis plan  
 
The statistical analysis in this study will subsist in 1) calculating the Kendall's 
correlation coefficient with 95% confidence intervals for each time point, separately for 
all subjects and in the subgroup with RVC≥5%, 2) plotting graphically the relationship 
between changes in arm volumes and BIS measurements, by time point, 3) calculate 
overall Kendall's tau stratifying by time point, i.e., evaluating concordant and discordant 
pairs within each time point only (35), 4) determining the change of BIS measurements 

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Version Date: 4/18/2018 
 
 
 
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corresponding to RVC=5% of volumetric measurements, 5) calculating area under ROC 
curve, for predicting volumetric RVC≥5% using BIS measurements, and tabulating 
diagnostic indices including specificity, sensitivity, positive prognostic value, 6) 
evaluating diagnostic characteristics of lymphedema diagnosis based on BIS using 3 
sigma method, and 7) assessing the association between patient-reported symptoms and 
each measurement method (using area under ROC and other diagnostic criteria). We will 
also evaluate the statistical distribution of BIS measurements and based on the shape of 
the distribution determined if BIS changes are better captured as absolute or as relative 
differences.  
 
6.8 Handling of missing data in the analysis  
 
RVC for volumetric changes and a corresponding quantity for BIS changes will 
be calculated only with patients with measurements both at the baseline and during 
follow-up. Time points with missing data will be excluded from the evaluation of the 
correlation between volumetric and BIS changes and, separately, between BIS changes 
and patient-reported symptoms for those patients who complete the LEFT-BC 
questionnaire.  
 
7.0 REFERENCES 
 
1. Clark B. SJ, Harlow W. Incidence and Risk of Arm Oedema Following 
Treatment for Breast Cancer: A Three-Year Follow-up Study. Q J Med. 
2005;98:343-348. 
2. Guide to Physical Therapy Practice. Vol 81. 2nd ed: American Physical 
Therapy Association; 2001. 
3. Armer J HP. Post-Breast Cancer Lymphedema in Aging Women: Self-
Management and Implications for Nursing. . Journal of Gerontological 
Nursing. 2005;31(5):29-39. 
4. Morrell RM, Halyard MY, Schild SE, Ali MS, Gunderson LL, Pockaj BA. 
Breast cancer-related lymphedema. Mayo Clin Proc. Nov 2005;80(11):1480-
1484. 
5. Ozaslan C, Kuru B. Lymphedema after treatment of breast cancer. Am J Surg. 
Jan 2004;187(1):69-72. 
6. Warmuth MA, Bowen G, Prosnitz LR, et al. Complications of axillary lymph 
node dissection for carcinoma of the breast: a report based on a patient survey. 
Cancer. Oct 1 1998;83(7):1362-1368. 
7. Paskett ED, Naughton MJ, McCoy TP, Case LD, Abbott JM. The 
epidemiology of arm and hand swelling in premenopausal breast cancer 
survivors. Cancer Epidemiol Biomarkers Prev. Apr 2007;16(4):775-782. 

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Version Date: 4/18/2018 
 
 
 
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8. Armer JM, Radina ME, Porock D, Culbertson SD. Predicting breast cancer-
related lymphedema using self-reported symptoms. Nurs Res. Nov-Dec 
2003;52(6):370-379. 
9. Leduc O, Leduc A. Rehabilitation protocol in upper limb lymphedema. Ann 
Ital Chir. Sep-Oct 2002;73(5):479-484. 
10. Kwan W, Jackson J, Weir LM, Dingee C, McGregor G, Olivotto IA. Chronic 
arm morbidity after curative breast cancer treatment: prevalence and impact 
on quality of life. J Clin Oncol. Oct 15 2002;20(20):4242-4248. 
11. Pain SJ, Vowler SL, Purushotham AD. Is physical function a more 
appropriate measure than volume excess in the assessment of breast cancer-
related lymphoedema (BCRL)? Eur J Cancer. Oct 2003;39(15):2168-2172. 
12. Armer JM, Stewart BR: A comparison of four diagnostic criteria for 
lymphedema in a post-breast cancer population. Lymphat Res Biol 3:208-17, 
2005 
13. Rockson SG, Rivera KK (2008) Estimating the population burden of 
lymphedema. Ann NY Acad Sci 1131: 147–154 
14. Cheville, A., McGarvey, C., Petrek., Russo, S., Thiadens, S., Taylor, M.  The 
Grading of Lymphedema in Oncology Clinical Trials.  Seminars in Radiation 
Oncology 2003; 13(3):214-225. 
15. Vignes, S., Arrault, M., Dupuy, A.  Factors Associated with Increased Breast 
Cancer-Related Lymphedema Volume.  Acta Oncologica 2007; 1-5. 
16. Williams, A., Franks, P., Moffatt, C.  Lymphoedema: Estimating the Size of 
the Problem.  Palliative Medicine 2005; 19:300-313. 
17. Petrek, J., Senie, R., Peters, M., Rosen, P.  Lymphedema in a Cohort of Breast 
Carcinoma Survivors 20 Years After Diagnosis.  Cancer 2001; 92(6):1368-
1377. 
18. Hayes SC, Janda M, Cornish B, et al: Lymphedema after breast cancer: 
incidence, risk factors, and effect on upper body function. J Clin Oncol 
26:3536-42, 2008 
19. Ward LC.  Is BIS ready for prime time as the gold standard measure? Journal 
of Lympheodema 2(2): 53-56, 2009 
20. Stout Gergich NL, Pfalzer LA, McGarvey C, et al: Preoperative assessment 
enables the early diagnosis and successful treatment of lymphedema. Cancer 
112:2809-19, 2008 
21. Armer, J.  The Problem of Post-Breast Cancer Lymphedema: Impact and 
Measurement Issues.  Cancer Investigation 2005; 1:76-83. 
22. Jain MS, Danoff JV, Paul SM: Correlation between bioelectrical spectroscopy 
and perometry in assessment of upper extremity swelling. Lymphology 43:85-
94, 2010 
23. Cornish BH, Chapman M, Hirst C, et al: Early diagnosis of lymphedema 
using multiple frequency bioimpedance. Lymphology 34:2-11, 2001 
24. Ward LC, Bunce IH, Cornish BH, et al. Multifrequency bioelectrical 
impedance augments the diagnosis and management of lymphedema in post-
mastectomy patients. Eur J Clin Invest 1992; 22:751-754.  

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Version Date: 4/18/2018 
 
 
 
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25. Czerniec SA, Ward LC, Refshauge KM, et al: Assessment of breast cancer-
related arm lymphedema--comparison of physical measurement methods and 
self-report. Cancer Invest 28:54-62, 2010 
26. Ancukiewicz M, Russell TA, Otoole J, et al: Standardized method for 
quantification of developing lymphedema in patients treated for breast cancer. 
Int J Radiat Oncol Biol Phys 79:1436-43, 2011 
27. Cornish BH, Bunce IH, Ward LC, et al: Bioelectrical impedance for 
monitoring the efficacy of lymphoedema treatment programmes. Breast 
Cancer Res Treat 38:169-76, 1996 
28. Hayes S, Cornish B, Newman B: Comparison of methods to diagnose 
lymphoedema among breast cancer survivors: 6-month follow-up. Breast 
Cancer Res Treat 89:221-6, 2005 
29. Ward LC, Czerniec S, Kilbreath SL: Operational equivalence of 
bioimpedance indices and perometry for the assessment of unilateral arm 
lymphedema. Lymphat Res Biol 7:81-5, 2009 
30. Ridner SH, Montgomery LD, Hepworth JT, et al: Comparison of upper limb 
volume measurement techniques and arm symptoms between healthy 
volunteers and individuals with known lymphedema. Lymphology 40:35-46, 
2007 
31. http://impedimed.com/knowledge-center/faqs/  
32. Petlund C. Lymph Stasis: Pathophysiology, Diagnosis and Treatment. 
Volumetry of Limbs. Boston: Olszewski & Waldeman; 1991:443-451. 
33. Tierney S, Aslam M, Rennie K, Grace P. Infrared optoelectronic volumetry, 
the ideal way to measure limb volume. Eur J Vasc Endovasc Surg. Nov 
1996;12(4):412-417 
34. Hollander M, Wolfe DA (1999). Nonparametric Statistical Methods, Wiley-
Interscience, 2nd ed. 
35. Newson R (2006). Confidence intervals for rank statistics: Somers' D and 
extensions. The Stata Journal  6:339-334 
 
8.0 APPENDICES  
 
8.1 Appendix 1: Partners/ DFHCC Lymphedema Studies  
 
8.1.2 Partners Protocol #: 1999-P-009256 
Study Outline: 
Data collection protocol for Breast Cancer database 
All patients who received treatment at MGH are eligible for entry 
Data includes: clinical and pathological data for surgical, radiation and medical 
oncology 
treatment, as well as basic demographic and risk factor information 
 
8.1.3 Partners Protocol#: 2005P-001038 
Study Outline: 
Data collection protocol for perometer measurements/database 
All patients who undergo a perometer measurement are eligible for entry 

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Data includes: clinical and pathological data for surgical, radiation and medical 
oncology treatment, perometer measurements as well as basic demographic and 
risk factor information. 
 
8.1.4 Partners Protocol#: 2008-P-000540 
Study Outline: 
Open to patients who undergo a pre-operative perometer reading and complete a 
pre-operative questionnaire 
At baseline measurement: 
1. Study explained 
2. Questionnaires with “Consent Fact Sheet” provided to patient 
3. Complete questionnaire prior to having perometer measurement 
Follow-up measurements: 
1. Patients asked to complete the LEFT-BC questionnaire at with follow-up visits 
2. Follow-ups defined as: after surgery, after chemotherapy, after radiation, 4-6 
month follow-up for 5 years, with any new symptoms outside of those time 
frames 
 
8.1.5 DFHCC Protocol #08-308 
 
Study Outline:  
Open to patients currently participating in Protocol# 2008-P-000540, who 
undergo two consecutive perometer measurements with RVC≥5% at a 4-8 week 
interval.  Patients with RVC 5-<10% are randomized within Group I –Mild 
Lymphedema (5-<10% RVC) to either observation or compression. Patients with 
RVC≥10% are randomized within Group II – Moderate Lymphedema (≥10-20% 
RVC) to compression or compression with night compression bandaging. 
Treatment intervention is for a duration of 12 weeks, after which patients undergo 
two follow-up measurements (week 16 and week 22-24) and subsequently return 
to screening per Protocol # 2008-P-000540.  
 
 
 
 
8.2 Appendix 2: LEFT- BC Questionnaire 
 
 
Lymphedema Evaluation Following  
Treatment for Breast Cancer Questionnaire 
 
 
 
Thank you for taking the time to complete this questionnaire. You can skip any questions 
that you do not want to answer. Lymphedema means swelling of the arm, hand, shoulder 
or upper body on the side where your cancer was treated.  
 

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The following questions will ask you about changes that have happened to your arm 
or body in the last month. 
 
Have you had a change in arm size?              
 Larger 
 Smaller        
 Constantly Changes     
  No 
change       
 
Have you had a change in shoulder size?        
 Larger 
 
 Smaller        
 Constantly Changes     
  No 
change       
 
Have you had a change in neck size?              
 Larger 
 Smaller        
 Constantly Changes     
  No 
change       
 
Have you had a change in how your sleeve fits?   
 
 Looser 
 Tighter        
 Constantly Changes     
  No 
change       
 
How has the way your sleeve cuff fits changed?   
 Looser 
 Tighter        
 Constantly Changes     
  No 
change       
 
How has the way your ring fits changed?       
 Looser 
 Tighter        
 Constantly Changes     
  No 
change       
 
 
The following questions will ask you about arm, breast, and chest symptoms you 
have experienced in the last month:   
 
Are you experiencing: 
None 
Mild 
Moderate 
Severe 
Not 
Applicable 
  Tenderness? 
0 
1 
2 
3 
 
  Swelling? 
0 
1 
2 
3 
 
  Redness? 
0 
1 
2 
3 
 
  Firmness/tightness? 
0 
1 
2 
3 
 
  Increased warmth in your arm? 
0 
1 
2 
3 
 
  Heaviness? 
0 
1 
2 
3 
 
  Numbness? 
0 
1 
2 
3 
 
  Stiffness? 
0 
1 
2 
3 
 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
24
  Aching? 
0 
1 
2 
3 
 
  Chest wall swelling? 
0 
1 
2 
3 
 
  Breast swelling? 
0 
1 
2 
3 
  Other symptoms  
       Please describe: 
 
 
 
 
 
 
 
Cording 
The next few questions will ask you about Cording. As your body heals following 
treatment for breast cancer, sometimes bands of tissue can form in your armpit or down 
you arm that look like strings or thin ropes. This is called cording. Please indicate if you 
have experienced any of the following symptoms. 
 
 
Do you feel pulling in any of the following areas? Check all that apply. 
      
   In your armpit that extends into the inside of your upper arm  
      
   Across the inside of your elbow  
     
   Into your forearm and wrist 
 
   Under your breast   
      
   None of the above 
 
Do you see or feel a thin cord or string in any of the following areas? Check all that 
apply. 
  In your armpit that extends into the inside of your upper arm  
        
  Across the inside of your elbow  
 Along your forearm or wrist 
 Under your breast extending towards your abdomen 
  None of the above 
 
 
 
 
Beliefs About Arm Use: 
The questions in this section ask about your beliefs about the use of your affected arm. 
Your affected arm is the side which you had or will be having surgery. Some questions 
in this section will ask about strenuous activities, examples of strenuous activities are: 
playing racquetball, cross country skiing, shoveling snow or cleaning a closet.  
 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
25
Arm swelling affects some women after breast cancer treatment.  We are interested in how 
you feel about this potential side-effect of treatment.  Please circle the number according 
to how strongly you agree or disagree with the statement.  
 
 
Strongly 
Agree 
Agree 
Disagree 
Strongly 
Disagree 
Don’t 
Know 
a. Having arm swelling would or does 
significantly change my lifestyle 
1 
2 
3 
4 
5 
b. The possibility of developing arm swelling 
or making it worse worries me 
1 
2 
3 
4 
5 
c. Doing strenuous activities with my affected 
arm puts me at risk of developing arm 
swelling or making it worse. 
1 
2 
3 
4 
5 
d. Strenuous work is part of my lifestyle so I 
must do it regardless of any advice given. 
1 
2 
3 
4 
5 
e. I plan to avoid any strenuous arm activities 
1 
2 
3 
4 
5 
f. I am more careful with my arm now than I 
was before my breast cancer treatment 
1 
2 
3 
4 
5 
g. I do not protect my arm in any way. 
1 
2 
3 
4 
5 
 
 
 
Use of Your Arm: 
The questions in this section ask about how you use your affected arm (the side which 
you had or will be having surgery). 
Please rate how well you could perform each of the activities when using your affected 
side, even if it is not your dominant arm or hand. Circle the number closest to how well 
you are able to complete each activity. 
 
 
 
Easily 
 
With Some 
Difficulty 
 
With Great 
Difficulty 
 
Unable 
to do  
Never 
Attempted, or 
Would Not 
Attempt 
a. Placing something on a shelf above 
my head 
1 
2 
3 
4 
5 
b. Drive a car for more than 30 
minutes 
1 
2 
3 
4 
5 
c. Pull a tight shirt on over my head 
1 
2 
3 
4 
5 
d. Unscrew a tight lid on a jar 
1 
2 
3 
4 
5 
e. Put on a bra that clips in the back 
1 
2 
3 
4 
5 
f. Carry a 10 pound grocery bag for 
10 minutes 
1 
2 
3 
4 
5 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
26
g. Sleep on my affected side for more 
than 10 minutes 
1 
2 
3 
4 
5 
h. Pull wet clothes out of the washing 
machine 
1 
2 
3 
4 
5 
i. Push a heavy piece of furniture 
1 
2 
3 
4 
5 
j. Dry my back with a towel 
1 
2 
3 
4 
5 
k. Chop potatoes into small cubes 
1 
2 
3 
4 
5 
l. Push open a heavy door 
1 
2 
3 
4 
5 
m. Clean a window above shoulder 
height 
1 
2 
3 
4 
5 
n. Vacuum for 30 minutes 
1 
2 
3 
4 
5 
o. Iron clothes for 15 minutes 
1 
2 
3 
4 
5 
p. Scrub a surface for 5 minutes 
1 
2 
3 
4 
5 
q. Catch a falling object with my 
affected hand 
1 
2 
3 
4 
5 
r. Carry a 10 pound bag over my 
shoulder 
1 
2 
3 
4 
5 
s. Type on a keyboard for 20 minutes 
1 
2 
3 
4 
5 
 
 
The questions in the next section will ask you about exercises for your affected arm. Your 
affected arm is the arm on the same side of your body that you had or will be having surgery 
as party of your breast cancer treatment. 
 
 
Did you do any exercises for your affected arm within the first few months after surgery? 
(Circle the letter that describes your exercise) 
 
 
a.    Yes 
 
b.    No  
 
Do you currently do any exercises for your affected arm? 
a.    Yes 
b.    No 
 
If you are still doing your exercises: How often are you doing exercises for your affected 
arm? 
 
a.    Daily 
 
b.    A few times per week 
 
c.    About once a week 
 
d.    About once a month 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
27
 
e.    Other. Please describe how often: ________________________________ 
 
 
Is there anything that may prevent or limit you from doing your arm exercises? Circle all 
of the statements that apply.  
 
a.    Nothing prevents or limits me from arm exercises 
 
b.    The exercises were too difficult 
 
c.    I have arm pain 
 
d.    My arm is too swollen 
 
e.    I don’t have time 
f. 
I worry that the exercises might make my arm swell 
g. I am too tired 
h. I am too confused about what to do 
i. Other. Please explain what other things may limit your exercise: 
_______________________________________________________________ 
 
Would you consider your regular daily activities strenuous on your arm(s)? 
 
a.     Yes 
 
b.     No 
 
c.     Don’t know 
 
About You: 
The questions in this section include a list of statements that other people with your 
illness have said are important. When discussing illness, we are asking about breast 
cancer. By circling one (1) number per line, please indicate how true each state has been 
for you during the past 7 days. 
 
Your Physical Well-Being 
 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Very much 
a. I have a lack of energy 
0 
1 
2 
3 
4 
b. I have nausea 
0 
1 
2 
3 
4 
c. Because of my physical 
condition, I have trouble 
meeting the needs of my family 
0 
1 
2 
3 
4 
d. I have pain 
0 
1 
2 
3 
4 
e. I am bothered by side effects of 
treatment 
0 
1 
2 
3 
4 
f. I feel ill 
0 
1 
2 
3 
4 
g. I am forced to spend time in bed 
0 
1 
2 
3 
4 
 
 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
28
Your Social/Family Well-Being 
 
Not at 
all 
A little bit 
Somewhat 
Quite a bit 
Very much 
a. I feel close to my friends 
0 
1 
2 
3 
4 
b. I get emotional support from 
my family 
0 
1 
2 
3 
4 
c. I get support from my friends 
0 
1 
2 
3 
4 
d. My family has accepted my 
illness 
0 
1 
2 
3 
4 
e. I am satisfied with family 
communication about my 
illness 
0 
1 
2 
3 
4 
f. I feel close to my partner (or the 
person who is my main support) 
0 
1 
2 
3 
4 
Regardless of your current level 
of sexual activity, please answer 
the following question.  If you 
prefer not to answer it, please 
check this box □ and go to the 
next section. 
g. I am satisfied with my sex life. 
0 
1 
2 
3 
4 
 
 
Your Emotional Well-Being 
 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Very 
much 
a. I feel sad 
0 
1 
2 
3 
4 
b. I am satisfied with how I am coping 
with  my illness 
0 
1 
2 
3 
4 
c. I am losing hope in the fight against 
my illness 
0 
1 
2 
3 
4 
d. I feel nervous 
0 
1 
2 
3 
4 
e. I worry about dying 
0 
1 
2 
3 
4 
f. I worry that my condition will get 
worse 
0 
1 
2 
3 
4 
 
Your Functional Well-Being 
 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Very much 
a. I am able to work (including 
work at home) 
0 
1 
2 
3 
4 
b. My work (including work at 
home) is fulfilling 
0 
1 
2 
3 
4 
c. I am able to enjoy life 
0 
1 
2 
3 
4 

Validity of BIS                                                              PI: Alphonse G. Taghian, MD PhD 
Version Date: 4/18/2018 
 
 
 
29
d. I have accepted my illness 
0 
1 
2 
3 
4 
e. I am enjoying the things I 
usually do for fun 
0 
1 
2 
3 
4 
f. I am content with the quality of 
my life right now 
0 
1 
2 
3 
4 
 
Additional Concerns 
 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Very much 
a. I have been short of breath 
0 
1 
2 
3 
4 
b. I am self-conscious about the way 
I dress 
0 
1 
2 
3 
4 
c. One or both of my arms are 
swollen or tender 
0 
1 
2 
3 
4 
d. I feel sexually attractive 
0 
1 
2 
3 
4 
e. I worry that other members of my 
family might someday get the 
same illness I have 
0 
1 
2 
3 
4 
f. I worry about the effect of stress 
on my illness 
0 
1 
2 
3 
4 
g. I am bothered by a change in 
weight 
0 
1 
2 
3 
4 
h. I am able to feel like a woman 
0 
1 
2 
3 
4 
i. I have certain parts of my body 
where I experience significant 
pain 
0 
1 
2 
3 
4 
 
 
 
 
 
 
 
 
8.3 Appendix 3: Risk Assessment  
 
 
 
 
 
 
 
 
 
 
Lymphedema Risk Assessment:  
MRN:  
Date:  
Blood Draws on Affected Side: ____ 
Blood Pressure Taken on Affected Side: ___ 
Injections: ____ 
Flights: ____ Total Hours: ___ 
Sleeve: _____ 
Trauma to Arm: ____ 
RVC: _____ 

Study ID#: ________________ 
Date Completed: ________________ 
 
 
 
Lymphedema Evaluation Following  
Treatment for Breast Cancer Questionnaire 
 
 
 
Thank you for taking the time to complete this questionnaire. You can skip any questions that you do not 
want to answer. Lymphedema means swelling of the arm, hand, shoulder or upper body on the side 
where your cancer was treated.  
 
 
 
The following questions will ask you about changes that have happened to your arm or body in the 
last month. 
 
Have you had a change in arm size?              
 Larger 
 Smaller        
 Constantly Changes     
  No change       
 
Have you had a change in shoulder size?        
 Larger 
 
 Smaller        
 Constantly Changes     
  No change       
 
Have you had a change in neck size?              
 Larger 
 Smaller        
 Constantly Changes     
  No change       
 
Have you had a change in how your sleeve fits?   
 
 Looser 
 Tighter        
 Constantly Changes     
  No change       
 
How has the way your sleeve cuff fits changed?   
 Looser 
 Tighter        
 Constantly Changes     
  No change       
 
How has the way your ring fits changed?       
 Looser 
 Tighter        
 Constantly Changes     
  No change       
 
 
 
 
 
 
 
 
 
 Continue on to the next page  
 

 
2 
The following questions will ask you about arm, breast, and chest symptoms you have experienced 
in the last month:   
 
Are you experiencing: 
None 
Mild 
Moderate 
Severe 
Not 
Applicable 
  Tenderness? 
0 
1 
2 
3 
 
  Swelling? 
0 
1 
2 
3 
 
  Redness? 
0 
1 
2 
3 
 
  Firmness/tightness? 
0 
1 
2 
3 
 
  Increased warmth in your arm? 
0 
1 
2 
3 
 
  Heaviness? 
0 
1 
2 
3 
 
  Numbness? 
0 
1 
2 
3 
 
  Stiffness? 
0 
1 
2 
3 
 
  Aching? 
0 
1 
2 
3 
 
  Chest wall swelling? 
0 
1 
2 
3 
 
  Breast swelling? 
0 
1 
2 
3 
 
  Other symptoms  
       Please describe: 
 
 
 
 
 
 
 
Cording 
The next few questions will ask you about Cording. As your body heals following treatment for breast 
cancer, sometimes bands of tissue can form in your armpit or down you arm that look like strings or thin 
ropes. This is called cording. Please indicate if you have experienced any of the following symptoms. 
 
 
Do you feel pulling in any of the following areas? Check all that apply. 
      
   In your armpit that extends into the inside of your upper arm  
      
   Across the inside of your elbow  
     
   Into your forearm and wrist 
 
   Under your breast   
      
   None of the above 
 
 Continue on to the next page  

 
3 
Do you see or feel a thin cord or string in any of the following areas? Check all that apply. 
  In your armpit that extends into the inside of your upper arm  
        
  Across the inside of your elbow  
 Along your forearm or wrist 
 Under your breast extending towards your abdomen 
  None of the above 
 
 
 
 
Beliefs About Arm Use: 
The questions in this section ask about your beliefs about the use of your affected arm. Your affected 
arm is the side which you had or will be having surgery. Some questions in this section will ask about 
strenuous activities, examples of strenuous activities are: playing racquetball, cross country skiing, 
shoveling snow or cleaning a closet.  
 
Arm swelling affects some women after breast cancer treatment.  We are interested in how you feel about 
this potential side-effect of treatment.  Please circle the number according to how strongly you agree or 
disagree with the statement.  
 
 
Strongly 
Agree 
Agree 
Disagree 
Strongly 
Disagree 
Don’t 
Know 
a. Having arm swelling would or does 
significantly change my lifestyle 
1 
2 
3 
4 
5 
b. The possibility of developing arm swelling 
or making it worse worries me 
1 
2 
3 
4 
5 
c. Doing strenuous activities with my affected 
arm puts me at risk of developing arm 
swelling or making it worse. 
1 
2 
3 
4 
5 
d. Strenuous work is part of my lifestyle so I 
must do it regardless of any advice given. 
1 
2 
3 
4 
5 
e. I plan to avoid any strenuous arm activities 
1 
2 
3 
4 
5 
f. I am more careful with my arm now than I 
was before my breast cancer treatment 
1 
2 
3 
4 
5 
g. I do not protect my arm in any way. 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
 
 
 
 Continue on to the next page   

 
4 
Use of Your Arm: 
The questions in this section ask about how you use your affected arm (the side which you had or will 
be having surgery). 
Please rate how well you could perform each of the activities when using your affected side, even if it is 
not your dominant arm or hand. Circle the number closest to how well you are able to complete each 
activity. 
 
 
 
Easily 
 
With Some 
Difficulty 
 
With Great 
Difficulty 
 
Unable 
to do  
Never 
Attempted, or 
Would Not 
Attempt 
a. Placing something on a shelf above 
my head 
1 
2 
3 
4 
5 
b. Drive a car for more than 30 
minutes 
1 
2 
3 
4 
5 
c. Pull a tight shirt on over my head 
1 
2 
3 
4 
5 
d. Unscrew a tight lid on a jar 
1 
2 
3 
4 
5 
e. Put on a bra that clips in the back 
1 
2 
3 
4 
5 
f. Carry a 10 pound grocery bag for 
10 minutes 
1 
2 
3 
4 
5 
g. Sleep on my affected side for more 
than 10 minutes 
1 
2 
3 
4 
5 
h. Pull wet clothes out of the washing 
machine 
1 
2 
3 
4 
5 
i. Push a heavy piece of furniture 
1 
2 
3 
4 
5 
j. Dry my back with a towel 
1 
2 
3 
4 
5 
k. Chop potatoes into small cubes 
1 
2 
3 
4 
5 
l. Push open a heavy door 
1 
2 
3 
4 
5 
m. Clean a window above shoulder 
height 
1 
2 
3 
4 
5 
n. Vacuum for 30 minutes 
1 
2 
3 
4 
5 
o. Iron clothes for 15 minutes 
1 
2 
3 
4 
5 
p. Scrub a surface for 5 minutes 
1 
2 
3 
4 
5 
q. Catch a falling object with my 
affected hand 
1 
2 
3 
4 
5 
r. Carry a 10 pound bag over my 
shoulder 
1 
2 
3 
4 
5 
s. Type on a keyboard for 20 minutes 
1 
2 
3 
4 
5 
 
 
 Continue on to the next page   

 
5 
The questions in the next section will ask you about exercises for your affected arm. Your affected arm is 
the arm on the same side of your body that you had or will be having surgery as party of your breast 
cancer treatment. 
 
 
Did you do any exercises for your affected arm within the first few months after surgery? (Circle the letter 
that describes your exercise) 
 
 
a.    Yes 
 
b.    No  
 
Do you currently do any exercises for your affected arm? 
a.    Yes 
b.    No 
 
If you are still doing your exercises: How often are you doing exercises for your affected arm? 
 
a.    Daily 
 
b.    A few times per week 
 
c.    About once a week 
 
d.    About once a month 
 
e.    Other. Please describe how often: ________________________________ 
 
 
Is there anything that may prevent or limit you from doing your arm exercises? Circle all of the statements 
that apply.  
 
a.    Nothing prevents or limits me from arm exercises 
 
b.    The exercises were too difficult 
 
c.    I have arm pain 
 
d.    My arm is too swollen 
 
e.    I don’t have time 
f. 
I worry that the exercises might make my arm swell 
g. I am too tired 
h. I am too confused about what to do 
i. Other. Please explain what other things may limit your exercise: _________________ 
_____________________________________________________________________ 
 
Would you consider your regular daily activities strenuous on your arm(s)? 
 
a.     Yes 
 
b.     No 
 
c.     Don’t know 
 
 
 Continue on to the next page   

 
6 
About You: 
The questions in this section include a list of statements that other people with your illness have said 
are important. When discussing illness, we are asking about breast cancer. By circling one (1) number 
per line, please indicate how true each state has been for you during the past 7 days. 
 
Your Physical Well-Being 
 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Very much 
a. I have a lack of energy 
0 
1 
2 
3 
4 
b. I have nausea 
0 
1 
2 
3 
4 
c. Because of my physical 
condition, I have trouble 
meeting the needs of my family 
0 
1 
2 
3 
4 
d. I have pain 
0 
1 
2 
3 
4 
e. I am bothered by side effects of 
treatment 
0 
1 
2 
3 
4 
f. I feel ill 
0 
1 
2 
3 
4 
g. I am forced to spend time in bed 
0 
1 
2 
3 
4 
 
 
Your Social/Family Well-Being 
 
Not at 
all 
A little bit 
Somewhat 
Quite a bit 
Very much 
a. I feel close to my friends 
0 
1 
2 
3 
4 
b. I get emotional support from 
my family 
0 
1 
2 
3 
4 
c. I get support from my friends 
0 
1 
2 
3 
4 
d. My family has accepted my 
illness 
0 
1 
2 
3 
4 
e. I am satisfied with family 
communication about my 
illness 
0 
1 
2 
3 
4 
f. I feel close to my partner (or the 
person who is my main support) 
0 
1 
2 
3 
4 
Regardless of your current level 
of sexual activity, please answer 
the following question.  If you 
prefer not to answer it, please 
check this box □ and go to the 
next section. 
g. I am satisfied with my sex life. 
0 
1 
2 
3 
4 
 
 
 Continue on to the next page  

 
7 
Your Emotional Well-Being 
 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Very much 
a. I feel sad 
0 
1 
2 
3 
4 
b. I am satisfied with how I am 
coping with  my illness 
0 
1 
2 
3 
4 
c. I am losing hope in the fight 
against my illness 
0 
1 
2 
3 
4 
d. I feel nervous 
0 
1 
2 
3 
4 
e. I worry about dying 
0 
1 
2 
3 
4 
f. I worry that my condition will get 
worse 
0 
1 
2 
3 
4 
 
Your Functional Well-Being 
 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Very much 
a. I am able to work (including work 
at home) 
0 
1 
2 
3 
4 
b. My work (including work at 
home) is fulfilling 
0 
1 
2 
3 
4 
c. I am able to enjoy life 
0 
1 
2 
3 
4 
d. I have accepted my illness 
0 
1 
2 
3 
4 
e. I am enjoying the things I usually 
do for fun 
0 
1 
2 
3 
4 
f. I am content with the quality of 
my life right now 
0 
1 
2 
3 
4 
 
Additional Concerns 
 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Very much 
a. I have been short of breath 
0 
1 
2 
3 
4 
b. I am self-conscious about the way 
I dress 
0 
1 
2 
3 
4 
c. One or both of my arms are 
swollen or tender 
0 
1 
2 
3 
4 
d. I feel sexually attractive 
0 
1 
2 
3 
4 
e. I worry that other members of my 
family might someday get the 
same illness I have 
0 
1 
2 
3 
4 
f. I worry about the effect of stress 
on my illness 
0 
1 
2 
3 
4 
g. I am bothered by a change in 
weight 
0 
1 
2 
3 
4 
h. I am able to feel like a woman 
0 
1 
2 
3 
4 
i. I have certain parts of my body 
where I experience significant 
pain 
0 
1 
2 
3 
4 

 
8