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Lymphedema: Impact on breast cancer survivors
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LYMPHEDEMA: IMPACT ON BREAST CANCER SURVIVORS
Copyright 2003
by
La Creachia Carraway
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
University of Southern California
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(EPIDEMIOLOGY AND APPLIED BIOSTATISTICS)
December 2003
La Creachia Carraway
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UMI Number: 1420359
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®
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UNIVERSITY OF SOUTHERN CALIFORNIA
THE GRADUATE SCHOOL
UNIVERSITY PARK
LOS ANGELES, CALIFORNIA 90089-1695
This thesis, written by
C ic a . c h iiL ^
under the direction o f h thesis committee, and
approved by all its members, has been presented to and
accepted by the Director o f Graduate and Professional
Programs, in partial fulfillment o f the requirements fo r the
degree o f
Decem ber 1 7 , 2003
Date _________________
Thesis Committee
‘i O B c rn S ^^ > ?h t>
S ~ h x n Aur.n P h,
" '
'hank Qiiliil&nd
Chair
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DEDICATION
I dedicate my years of hard work at USC to my husband, Kevin Carraway, my
daugherter, India Carraway, my parents, brother, grandparents, in-laws, and the rest of
my family. I could not have done it without their love and support. Also, I would like to
give a special thanks to my family members who flew to Los Angeles from San
Francisco for approximately six months to baby-sit India, so I could continue taking
classes after giving birth. To my beloved grandfather, Joe Brice, though you passed
away a month or so before I stared USC and before I gave birth to India, I continue to
feel your presence. I know that you will continue to watch over me as well as the rest of
the family to assure that we are safe and that we continue to make wise decisions.
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ACKNOWLEDGEMENTS
Leslie, I feel as though I was so fortunate to have had the opportunity to work closely
with you for the last three years. I have gained a wealth of knowledge and
experience that will only help my career prosper. You have been a great mentor, and
I only hope to follow in your footsteps as I advance in this field. Also, I would like
to take this opportunity to thank Jane Hailey for all of her help and support. To my
peers, you have made this a wonderful experience at USC. It breaks my heart that
we will no longer be seeing each other everyday, but the time has come for us to
move on and branch off into our careers.
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TABLE OF CONTENTS
Dedication ii
Acknowledgements iii
Abstract vi
List of Tables v
Chapter 1: Introduction 1
Chapter 2: Materials and Methods
Study subjects 4
Baseline data collection 4
30-month follow-up 5
Treatment data 6
Quality of Life 6
Concerns with experiencing lymphedema 8
Measurements of fatigue using Piper Fatigue Scale . 8
Chapter 3: Statistical Methods 10
Chapter 4: Results 11
Chapter 5: Discussion 33
References 36
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V
LIST OF TABLES
Table 1. Characteristics of participants (number and percent) ....................... 12
Table 2. Patient treatment status by stage of disease (number and percent) ........ 13
Table 3. Frequency of breast prosthesis and reconstructive surgery by stage of
disease (percent).............................................................................. 16
Table 4. Treatment and impact of lymphedema ..... ...................................1 7
Table 5. Lymphedema status by treatment (number and percent) ...... 20
Table 6. Frequency with which women experienced chest wall symptoms
in the past 3 months: By Race
21
Table 7. Frequency with women experienced chest wall symptoms in the
past 3 months according to lymphedema status and type of surgery
(number and percent) ....... .23
Table 8. Frequency with which women experienced symptoms in arm(s)
in the past 3 months: By Race
...... ...25
Table 9. Frequency with which women experienced symptoms in the arm(s)
in past 3 months according to lymphedema status and type of surgery
26
Table 10. Overall fatigue mean score by age, stage of disease,
and lymphedema status (number and percent)
................................................................................................. 28
Table 11. Adjusted odds ratios of lymphedema status ............................... 29
Table 12. Adjusted odds ratios of lymphedema status stratified by age ............ 31
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vi
ABSTRACT
We evaluated the characteristics of women developing lymphedema
following their breast cancer diagnosis and determined the frequency of symptoms
associated with lymphedema in a cohort of African American and Caucasian patients
aged 35 to 64 years at the time of diagnosis. African American and Caucasian
patients reported similar prevalences of lymphadema, although symptom profiles
differed somewhat. Multivariate logistic regression analyses revealed that body
mass index and chemotherapy were important predictors of the development of
lymphadema, whereas type of surgery and treatment with radiation therapy or
tamoxifen were not. Older women, aged 55 to 64 years at diagnosis were less likely
to have developed lymphedema than younger women during the 30 months of
follow-up after breast cancer diagnosis.
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1
CHAPTER I - INTRODUCTION
Mortality rates of breast cancer are gradually declining as a result of the
widespread use of screening mammography and effective adjuvant therapy (1,2).
Today, it is no surprise that many women diagnosed with breast cancer can expect to
live just as long as women of the same age group who do not have breast cancer (1).
For these women living with breast cancer, effective prevention and management of
treatment sequelae to improve quality of life have taken on increasing importance.
Sentinel-node biopsy, which may lead to the elimination of axillary-node
dissection in women with breast cancer, offers promise for decreasing the incidence
of lymphedema associated with standard axillary lymph-node dissection (1,3).
Although rarely life threatening, lymphedema is a debilitating condition that results
often from axillary-node dissection. Breast cancer patients who receive radiation to
the axillary area are at an increased risk of lymphedema compared to patients who do
not receive radiation (1). In a previous study, it was reported that 60% of women
who had undergone a radical mastectomy had lymphedema followed by 30% of
women treated with a modified radical mastectomy or breast-conserving surgery (1).
Lymphedema is defined by Price et al. as lymph nodes and vessels being
removed or damaged during breast cancer surgery which results in protein-rich
lymphatic fluid accumulating in the interstitial spaces of soft tissue around the
operative site extending to the arm, the entire trunk, and any remaining breast tissue
on the affected side (4). It is more common in obese women and in women who are
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2
older than 60 years of age due to the loss of connection between lymph vessels and
veins, which tends to be more apparent in these women (5).
This condition is usually diagnosed clinically by a physical examination and
by reviewing the medical history of the patient (6). Sequential circumferential
measurement, which allows for arm volume to be measured, is an inexpensive
method that is used to evaluate the extent of lymphedema to the affected arm.
Today, volumetric measurements are most often used as a way to evaluate
lymphedema. Measured differences greater than 2 cm between the affected arm and
the normal arm are considered clinically significant (6). Newer methods now have
been developed for the diagnostic evaluation of lymphedema such as bioelectrical
impedence, which quantifies the amount of fluid that has accumulated in the affected
area and lymphoscintigraphy, which allows visualization of the lymphatic system
(6).
Furthermore, lymphedema may develop at any time and can cause a painful
unsightly swollen arm, limited arm movement, increased risk of infection, numbness,
tightness, tension, heaviness, hardness, redness, and dryness of skin to the affected
area. Although studies on the treatments of lymphedema exist, results have been
inconsistent.
The psychological impact of lymphedema has been documented and studies
have shown several common psychological effects associated with lymphedema.
These psychological effects include feelings of anxiety, isolation, sexual
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3
dysfunction, and distress as patients feel their quality of life has been compromised
as a result of their condition (6). In addition, some women experience such problems
because of the limited knowledge physicians have regarding their condition, the few
treatment options available, issues relating to personal relationships and body image,
and sudden changes to daily activities (6).
The purpose of this study is to compare the rates of lymphedema in African-
American and Caucasian breast cancer survivors, characterize symptoms associated
with lymphedema, and determine predictors of lymphedema.
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4
CHAPTER II - MATERIALS AND METHODS
Study Subjects
The HEAL (Health, Eating, Activity, and Lifestyle) Study is a multi-center
longitudinal study of breast cancer prognosis with patients recruited in Los Angeles,
New Mexico and Seattle. The Los Angeles Center at the University of Southern
California included patients who participated in one of two population-based case-
control studies, a study of in situ breast cancer (INSITU) and the Women’s
Contraceptive and Reproductive Experiences (CARE) Study of invasive breast
cancer, which were conducted simultaneously. These two studies evaluated breast
cancer risk factors among women living in Los Angeles County who were 35 to 64
years of age. Breast cancer patients who were eligible for the HEAL Study were
African-American women residing in Los Angeles County at the time of their
diagnosis and who were diagnosed with a first primary breast cancer (stages 0 to
IIIA) between May 1995 and May 1998. A total of 367 African-American women
who participated in the CARE or INSITU studies satisfied the above criteria. We
also recruited Caucasian women from the CARE or INSITU studies who satisfied
the above criteria; these women were not part of the HEAL Study. Informed consent
was provided and signed be each of the participants. The University of Southern
California Research Committee approved the study procedures, in accordance with
assurances approved by the U.S. Department of Health and Human Services.
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5
Baseline data collection
Baseline information was collected during in-person interviews. All baseline
interviews were conducted within 18 months of diagnosis, with a mean interval of
6.0 months between diagnosis and interview and a median of 4.8 months. The
questionnaire included items about age, height, reproductive history, use of
hormones, screening history, family history of breast, ovarian, and endometrial
cancer, smoking and alcohol history, and lifetime physical activity. Weight at ages
18, 35, and 50 years and 5 years prior to diagnosis were obtained by self-reporting
during the interview. Usual adult weight was defined as weight 5 years prior to
diagnosis. In addition, usual adult Body Mass Index (BMI) was defined as adult
usual weight (kg) divided by adult height squared (M2 ).
30-month Follow-up
The HEAL Study follow-up interview, which targeted only the African-
American women, took place approximately 30 months (+/-3 months) after the
diagnosis of breast cancer (24 months after the initial interview for the Women’s
CARE Study or the in situ study which occurred at approximately 6 months after
diagnosis). Of the 367 eligible women who completed the CARE or INSITU study
interviews, 262 completed the 30-month follow-up interview. Reasons for
nonparticipation included: inability to locate participants after CARE interview (55
women), death or severe illness (21 women), refusal to participate at time of follow-
up contact (28 women), and 1 gate-keeper refusing contact with the patient.
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6
For the HEAL Study, in-person interviews were conducted at participants’
homes as they had been conducted previously for the CARE and INSITU studies.
Additional data collected during the interview included information regarding the
woman’s breast disease and treatment, other medical conditions and hospitalizations
since her breast cancer diagnosis, and her current menstrual status, medication use,
use of hormonal therapy (HRT), recent diet, physical activity patterns, and tobacco
use. Upon completing the interview, anthropometric measurements were collected
and blood samples were drawn.
Treatment data
During the 30-month follow-up interview, diagnostic and treatment
information was obtained from self-reports (for tamoxifen therapy) from the USC
Cancer Surveillance Program, the population-based cancer registry for Los Angeles
County, a member of the Surveillance, Epidemiology and End Results (SEER)
program of the National Cancer Institute (NIH) which records first course of
treatment (covering 6 months following diagnosis).
Quality of Life (QOL)
The Quality of Life study, which targeted both the African-American and
Caucasian women, was designed to assess the impact of breast cancer on the
patients’ lives. All African-American participants in the HEAL Study were eligible
for this study and Caucasian breast cancer patients were specifically selected from
the CARE and INSITU studies to participate in the QOL study. The same selection
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7
criteria for eligibility were used for both groups of women. 367 Caucasian women
who participated in the INSITU and CARE studies and the 262 African-American
women who participated in the HEAL 30 month follow-up study were considered
eligible to participate in the QOL study. Of the 367 Caucasian women, 271
completed a QOL telephone interview. Reasons for nonparticipation included:
inability to locate (30 women), death or severe illness (34 women), and refusal to
participate within study time frame (32 women). Of the 262 African American
women who completed the HEAL follow-up interview, 224 completed the QOL
telephone interview. Reasons for nonparticipation included death or severe illness
(8 women), inability to locate (4 women), and refusal to participate within the study
time frame (26 women).
Telephone interviews, conducted by a single interviewer, were done during
times that were most convenient for the participants. Verbal informed consent was
given prior to the interview. The questionnaire included information on patients’
participation in support groups, their feelings about their medical team, symptoms
experienced in the chest wall and arm(s) during the past three month since their
diagnosis. Additional information on patients’ experience with arm lymphedema,
feelings about their quality of life, behavioral, mental and emotional changes in their
daily activities that could be a result of fatigue, experience with personal
relationships and body image, experiences with stress, and their feelings of physical
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8
health were included. In this report we focus on the patients’ experience with
lymphedema in relation to their treatment status, age, and body mass index.
Concerns with experiencing lymphedema
Information relating to the presence or absence of lymphedema, symptoms
associated with lymphedema, and treatments used for lymphedema was obtained by
the interviewer. We also assessed the impact that lymphedema had on patients’ lives
using the Wesley Clinic Lymphoedema Scale derived from the “Functional Living
Index—Cancer” (FLIC). This index, which consisted of five items: physical well
being, psychological state, family situation, sociability, and nausea, focused on the
quality of life of lymphedema patients. The subjects responded to each item using a
rating of 1 to 7, with a score of 7 indicating a high score thus a high quality of life.
(Mirolo BR. et al, 1995).
Measurements of Fatigue using Piper Fatigue Scale (PFS)
We also measured the level of fatigue that patients’ experienced within the 4
months prior to this interview. Fatigue was measured using the Piper Fatigue Scale
which is divided into 4 subscales: behavioral/severity, which assesses changes in
activities of daily living that could result from fatigue, and affect, sensory, and
cognitive mood, which reflect the mental and emotional symptoms related to fatigue.
The subjects responded to each item using a simple rating of intensity on a 0 to 10
scale, with a score of 10 indicating a high level of fatigue. The final score, an overall
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. 9
fatigue mean score, consisted of adding the 22 item scores together and dividing by
22 to retain the 0 to 10 intensity scale metric (Piper BF. et a!., 1998).
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10
CHAPTER 1 1 1 - STATISTICAL ANALYSIS
We compared characteristics of African American and Caucasian women as
well as women with and without lymphedema using Fisher’s exact test. We used
logistic regression methods to compute odds ratios and 95 percent confidence
intervals assessing predictors of lymphedema. Multivariate models were used to
estimate the joint effects of age, race, body mass index, chemotherapy, tamoxifen,
type of surgery (i.e. lumpectomy or mastectomy) and radiation treatment on
lymphedema risk. In addition, we conducted separate multivariate analyses
stratifying by age classifying women as younger than 55 years of age and 55 years of
age or older at diagnosis. We also conducted tests for trend across ordinal categories
of body mass index. All analyses were performed using Statistical Analysis System
software (SAS).
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11
CHAPTER IV - RESULTS
The mean age at diagnosis for African-American patients is 50.9 (7.7) and for
Caucasian patients is 50.1 (8.8) (Table 1). African-American patients tended to have
a greater BMI than Caucasian patients with 27% of African-Americans considered
obese and only 9% of Caucasians (BMI > 30). 44% of African-American women
and 54% of Caucasian women had localized breast cancer, whereas 33% of the
African-American patients and 26% of the Caucasian patients had breast cancer with
regional nodes only. Among other characteristics, over 50% of the women in both
ethnic populations, were not currently married or in a partnered relationship at time
of Quality of Life interview, African-American patients are more likely not to be
currently married or in a partnered relationship than Caucasian women (P = .0001).
As for Caucasian women, 60% with in-situ breast cancer and 66% with
localized breast cancer had undergone a lumpectomy or partial mastectomy and only
32% with regional breast cancer with direct extensions and nodes had undergone the
same types of surgery (Table 2). The majority of Caucasian women who had
undergone a modified radical mastectomy had localized breast cancer and had
regional breast cancer with nodes only.
In comparison, 50% of African-American patients with insitu breast cancer
and 51% with localized breast cancer had undergone a lumpectomy or partial
mastectomy, whereas only 39% of those with regional breast cancer confined to
lymph nodes only had undergone a lumpectomy.
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Table 1. Baseline characteristics of participants
African-Americans
n * 224
Caucasians
n = 271 p-value*
n {% ) n (%)
Age at diagnosis
35-44 51 ( 23) 89 { 33) 0.02
45-54 94 { 42) 86 { 32)
55-64 79 ( 35) 86 { 35)
Mean age at diagnosis (+ SD) 50.9 (+ 7.7) 50.1 {+ 8.8)
Body mass index (kg/meters squared)
<20 10 ( 4) 36
( 13)
<.00001
20.0-24.9 75 ( 34) 135 { 50}
25.0-27.9 53 ( 24) 54 { 20)
28.0-29.9 25 (1 1 ) 21 { 8)
>=30
Missing
60 { 27)
1
25
0
( 3)
Mean BMI i±SD) 27.6 (+ 5.8) 24.2 (±4.6)
Currently married or in partnered
relationship*®
Yes 101 ( 46) 70 ( 26) 0.0001
No
Missing
121 { 55)
2
198
2
( 74)
Stage of disease
in-situ 48 ( 21) 50 ( 18) 0.19
Localized 99 ( 44) 146 ( 54)
Regional nodes only 73 ( 33) 71 ( 26)
Regional direct extension and nodes 4 ( 2) 4
{ D
* Fisher's Exact Test 2-sided p-vaiue
* * Measured at Quality of Life interview
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13
Table 2. Patient treatment status by stage of disease_______________________________
Stage of Disease
Regional
direct
Regional extentions &
insitu Localized nodes only nodes
n (% } n (%) n (%) n {%}
ype of Surgery
Caucasians
Partial mastectomy 24 ( 48) 84 ( 58) 22 ( 31) 0{ 0)
Lumpectomy 6 { 12) 11 (
8) 1 { 1) 0 ( 0)
Reexcision biopsy 4 ( 8) 7 (
5) 3 ( 4) 0 ( 0)
Quadarrtectomy 0{ 0) 0{ 0) I f 1) Of 0)
Segmental mastectomy 2 { 4) 0 ( 0) 2 ( 3) 0 ( 0)
Subcutaneous mastectomy
2 (
4) 0{ 0) 1 f 1) 0 ( 0)
Total simple mastectomy 7{ 14) 4 ( 3) 0{ 0) Of 0)
Modified radical mastectomy
5 (
10) 39 ( 27) 40 ( 56) 4 (100)
Radical mastectomy 0 ( 0) 1 ( <1) 0 ( 0) 0 ( 0)
Mastectomy 0{ 0) 0( 0)
1 { 1)
0 ( 0)
African-Americans
Partial mastectomy 19 C 41) 43 {
44)
28 f 39) 1 { 25)
Lumpectomy 4 ( 9) 7{ 7) Of 0) Of 0)
Reexcision biopsy 1 { 2) 7 ( 7) K 1)
Of 0)
• Guadantedomy 1 ( 2) 0 {
0)
1 f 1)
Of 0)
Segmental mastectomy
1 (
2) 4 ( 4)
1 ( 1)
Of 0)
Total simple mastectomy 9{ 20) 3 f
3) 2 ( 3) 0{ 0)
Modified radical mastectomy
11 (
24) 34 ( 35) 38 { 53) 3 { 75)
Mastectomy 0 { 0) 0 { 0) I f 1) 0{ 0)
'amoxlfen treatment
Caucasians
No 37 { 74) 64 ( 44) 24 ( 34) 1 { 25)
Yes 13 ( 26) 82 ( 56) 47 f 66) 3 ( 75)
African-Americans
No 31 { 65) 41 { 41) 27 ( 37) 1 { 25)
Yes 17 ( 35) 58 { 59) 46 { 63) 3 ( 75)
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Table 2, Patient treatment status by stag® of disease - Continued
Stage of Disease
insitu Localized
Regional
direct
Regional extentions &
nodes only nodes
Radiation Therapy
Caucasians
No
Yes
African-America ns
No
Yes
si (%) n (% )
39( 78} 6 0 (4 1 )
11 ( 22) 86 ( 59)
38 ( 79) 56 ( 57)
10( 21) 43( 43)
n (%)
n (% )
34 ( 48) 3 ( 75)
37 ( 52) 1 ( 25)
43 ( 59) 3 ( 75)
3 0 (4 1 ) 1 ( 25)
Chemotherapy
Caucasians
No
Yes
African-Americans
No
Yes
50 (100) 106 ( 73)
0(0) 40 { 27)
48(100) 70( 71)
0 ( 0) 29 ( 28)
12 (1 7 ) 1 ( 25)
59 ( 83) 3 ( 75)
11 (1 5 ) 1 ( 25)
62 ( 85) 3 ( 75}
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15
More Caucasian and African-American patients who had undergone a
lumpectomy or partial mastectomy had undergone beam radiation than patients who
had undergone other types of radiation such as radioisotopes, a combination of beam
radiation with radioisotopes, or radiation not otherwise specified (Caucasians n =
101 (74%); African-Americans n = 61 (73%). Of all the women, only five percent
received radioisotopes, a combination of beam radiation with radioactive implants or
radioisotopes, or radiation that is not otherwise specified (data not shown).
African-American patients with invasive breast cancer were less likely to
have reconstructive surgery and were more likely to use a breast prosthesis than
Caucasian patients (Table 3).
African-American and Caucasian women did not differ in the frequency with
which they experienced lymphedema (p = 0.12) (Table 4). Among those with
lymphedema the proportion of women who received or continued to receive
treatment for their lymphedema did not differ in the groups (45% for African-
Americans and 50% for Caucasians, p = 0.71). Women who received treatment were
most likely to use compression by elastic sleeves or gloves, massage therapy, arm
elevation, and physical activity'. Among African-American 82% used compression
by elastic sleeves or gloves, 64% used arm elevation, and 54% used massage
therapy. In contrast, 97% of Caucasian patients treated for lymphedema used
massage therapy, followed by 93% who used a m elevation, whereas 76% used
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16
Table 3, Frequency of breast prosthesis and reconstructive
surgery by stage of disease_____________________________
Stage of
Disease
Regional direct
Regional extentions &
insitu Localized nodes only nodes _
n {% ) n (% ) n (% ) n (% )
Breast prosthesis
Caucasians
No 42 ( 34} 126 ( 86) 50 { 70) 1 ( 25)
Yes 8 ( 18) 20 ( 14) 21 ( 30) 3{ 75)
African-Americans
No 34 { 71} 72 { 73) 34 ( 47) 2 { 50)
Yes 14 { 29) 27 ( 27) 39 { 53) 2 { 50)
teconstructive surgery
Caucasians
No 39 { 78) 115 ( 79) 44 ( 62) 2 { 50)
Yes 11 ( 22) 31( 21) 27 ( 38) 2 ( 50)
African-Americans
No 35 ( 73) 86 ( 87) 83 ( 86) 3 { 75)
Yes 13 { 27) 13 ( 13) 10 { 14) 1 ( 25)
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Table 4, Treatment and impact of lymphedema
African-
Americans Caucasians
n (% ) n (% )________ p-vaiue*
Experienced lymphedema at any time
since diagnosis
No 162 (72) 213(79) 0.12
Yes 62 (28) 58 (21)
Have you received or do you continue
to receive treatment for lymphedema
No
Yes
34 (55)
28 (45)
29 (50)
29 (50)
0.71
Type of treatment used for lymphedema
None 34 (55) 29 (50)
At least one** 28 (45) 29 (50)
Compression by pneumatic pump 4(14) 6(21}
Compression by elastic sleeves or gloves 23 (82) 22 (76)
Support garments/wrappings 9(32) 3(31)
Massage therapy 15 (54) 28 (97)
Manual lymphatic drainage 6(21) 13 (45)
Arm elevation 18 (64) 27 (93)
Microwave heating 1 (4) 1 ( 3)
Diuretics 7(25) 2 { 7)
Antibiotics 2 ( 7) 5 (17)
Coumarin drug therapy 0 ( 0) 0 ( 0)
Other drug therapy 1 ( 4) 3(10)
Physical activity 10(36) 21 (72)
Surgery 0 ( 0) 3(10}
Did any of these treatments help
No
Yes
Is lymphedema still present
No
Yes
5(18)
23 (82)
Of 0)
29 (100)
0.02
6 (10)
56 (90)
11 (19)
47(81)
0.19
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18
Table 4. Treatment and impact of lymphedema -
Continued
African-
Americans
n (% )
Caucasians
n 1%)
Activities which are limited a lot by
lymphedema*"
Cooking 13(21) 6(11)
Physical fitness activity 11 (21) 14 (24)
Cleaning house 14 (23) 11 (13)
Full or part-time job 5(14) 6(15)
Volunteer work 0 ( 0) 3(19)
Driving 5 ( 9) 3 ( 5)
Shopping 14 (23) 11 (19)
Gardening 4 (19) 8 (25)
'Fisher’s Exact Test 2-sided p-value
“ For each treatment type the percent represents the proportion of women
treated for lymphedema
who used a specific treatment
'“ Percent represents the proportion of women with lymphedema who are limited in
performing each activity
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19
compression by elastic sleeves or gloves. Of the 29 Caucasian women who used at
least one treatment to manage their lymphedema, all 29 women appear to have had a
successful outcome. On the other hand, only 82% of the African-American women
appear to have had a successful outcome (p = 0.02). Of the 62 African-American
patients who experienced lymphedema at the time since their diagnosis,
56 (90%) continue to experience lymphedema. In comparison, 47 (81%) of the
Caucasian women who initially experienced lymphedema continued to experience
lymphedema after diagnosis. Our results indicate that the three most common
activities that are limited by lymphedema are physical fitness, cleaning house, and
shopping. Both African-American and Caucasian women who had chemotherapy
were more likely to develop lymphedema respectively (p = 0.0038; p = 0.03)
(Table 5).
African-American and Caucasian patients differed in types of symptoms
experienced in their chest wall, in the past 3 months before interview. African-
American patients tended to report feeling of pins and needles, numbness, skin
sensitivity, and tightness more frequently than Caucasian patients (Table 6).
Patients with and without lymphedema differed in types of sensations felt in
their chest wall in the past 3 months before interview. Patients with lymphedema
reported feeling pins and needles, numbness, skin sensitivity, swelling, tenderness,
and tightness more frequently than unaffected patients. Moreover, patients who had
undergone a lumpectomy or mastectomy differed in types of sensations felt in the
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Table 5, Lymphedema status by treatment (Number and Percent)
Surgery
Lumpectomy
Mastectomy
Radiation
No
Yes
Chemotherapy
No
Yes
Tamoxifen
No
Yes
African-American P-value* Caucasian
Lymphedema Lymphedema
No Yes No Yes
P-value* All women P-value*
Lymphedema
No Yes
n (%) n (%)
88 (56)
70 (44)
31 (50)
31 (50)
0.46
n (%) n <% )
131 (62) 36 (62)
82 (39) 22 (38)
100 (62) 40 (65) 0.76 112(53) 24 (41)
62 (38) 22 (35) 101 (47) 34 (59)
104(64) 26 (42) 0.0038 140 (66) 29 (50)
58 (36) 36 (58) 73 (34) 29 (50)
72 (44) 28 (45) 1.0 100 (47) 26 (45)
90 (56) 34 (55)___________ 113(53) 32 (55)
n (%) n (%)
1.0 219(59) 67 (56) 0.59
152 (41) 53 (44)
0.14 212 (57) 64 (53) 0.60
163 (43) 56 (47)
0.03 244 (65) 55 (46) 0.00025
131 (35) 65 (54)
0.88 172 (46) 54 (45) 0.92
203 (54) 66 (55)________
“Fisher's Exact Test 2-sided p-value
O
Table 6, Frequency with which women experienced chest wall symptoms
in the past 3 months: By Race_____________________________________
All Women
n {% )
African-
Americans
n (% }
Caucasians P-value*
n (%)
Pins and Needles
Never, Rare 387 (78) 162 (72) 225 (83) 0.00089
Sometime 68 (14) 33 (15) 35 (13)
Often, Very Often 40 ( 8) 29(13) 1 1 (4 )
Numbness
Never, Rare 327 (66) 160 (71) 167 (61) 0.06
Sometime 60 (12) 22 (10) 38 (14)
Often, Very Often 108(22) 42 (19) 66 (24)
Skin Sensitivity
Never, Rare 320 (65) 132 (59) 188(69) 0.03
Sometime 101 (20) 49 (22) 52 (19)
Often, Very Often 74 (15) 43 (19) 31 (11)
Swelling
Never, Rare 443 (89) 200 (89) 243 (90) 0.95
Sometime 23(5) 10 (4) 13 ( 5)
Often, Very Often 29 {6) 14(6) 15 ( 6)
Tenderness
Never, Rare 297 (60) 138 (62) 159 (59) 0.52
Sometime 110(22) 51 (23) 59 (22)
Often, Very Often 88 (18) 35 (16) 53 (20)
Tightness
Never, Rare 328 (68) 148 (66) 180 (66) 0.70
Sometime 95(19) 46 (21) 49 (18)
Often, Very Often 72 (15) 30(13) 42 (16)
Pain
Never, Rare 371 (75) 172 (77) 199 (73) 0.61
Sometime 83(17) 36 (16) 47 (17)
Often, Very Often 41 ( 8) 16 ( 7) 25 ( 9)
*FIsher's Exact Test 2-sided p-value comparing African-
Americans and Caucasians
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2 2
chest wall. Those who had undergone a mastectomy reported feeling pins and
needles, numbness, tightness, and pain more frequently than those who had a
lumpectomy (Table 7).
Similarly, African-American and Caucasian patients differed in types of
sensations felt in their arm(s) in the past 3 months. African-American patients
reported feeling pins and needles, numbness, skin sensitivity, and swelling more than
Caucasian patients (Table 8).
Women who had undergone a mastectomy tended to report experiencing pins
and needles, skin sensitivity, swelling, and tightness in their arm(s) in the past 3
months more frequently than those who had undergone a lumpectomy (Table 9).
Overall fatigue, as measured by the Piper Fatigue Scale, was unrelated to age,
stage of disease or lymphedema status (Table 10).
Older women (55-64 years) were less likely to report lymphedema (Table
11). Those women with BMI between 25 to 29.9 kg/m2 were 2 times as likely to
experience lymphedema as women with BMI of less than. 25. The odds of
experiencing lymphedema was nearly 3 times greater for women with a BMI of 30
or more than for those with BMI of less than 25 (p tre n d <0.0001). The risk of
lymphedema was also associated with having chemotherapy treatment. After
adjusting for age, BMI, race, tamoxifen, surgery, and radiation, women who received
chemotherapy were nearly 2 times more likely to experience lymphedema than
women who had not received chemotherapy.
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Table 7. Frequency with which women experienced chest wall symptoms in the past 3 months according to
lymphedema status and type of surgery ' ________ __________ _______________________ _______________ ___
Lymphedema p-value" Type of Surgery** p-value*
No Yes Lumpectomy Mastectomy
n (%) «(%) n (% ) n (% )
Pins and Needles
Never, Rare 304(81) 83 (69) 0.002 236 (83) 148 (72) 0.02
Sometime 50 (13) 18(15) 33 (12) 35 (17)
Often, Very Often 21 ( 6) 19 (16) 17 ( 6) 22 (11)
Numbness
Never, Rare 259 (69) 68 (57) 0.04 207 (72) 116(57) 0.001
Sometime 43 (12) 17(14) 30(10) 30 (15)
Often, Very Often 73 (20) 35 (29) 49(17) 59 (29)
Skin Sensitivity
Never, Rare 255 (68) 65 (54) 0.004 192(67) 124(60) 0.31
Sometime 75 (20) 26 (22) 53 (19) 48 (23)
Often, Very Often 45 (12) 29 (24) 41 (14) 33 (16)
Swelling
Never, Rare 352 (94) 91 (76) <.00001 257 (90) 182 (89) 0.75
Sometime 11 ( 3) 12(10) 14 ( 5) 9 ( 4)
Often, Very Often 12 ( 3) 17(14) 15 ( 5) 14 ( 7)
Tenderness
Never, Rare 239 (64) 58 (48) 0.01 162 (57) 131 (64) 0.06
Sometime 77(21) 33 (28) 63 (22) 47(23)
Often, Very Often 59(16) 29 (24) 61 (21) 27 (13)
Tightness
Never, Rare 264 (70) 64(53) 0.0001 202 (71) 123(60) 0.04
Sometime 71 (19) 24 (20) 50 (18) 44(21)
Often, Very Often 40(11) 32 (27) 34 (12) 38 (19)
N >
U J
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Table 7. Frequency with which women experienced chest wall symptoms In the past 3 months according to
lymphedema status and type of surgery - Continued______________________________________________ ______________
Pain
Never, Rare 288 (77) 83 (69) 0.12 209 (73) 158 (77) 0.03
Sometime 61 (16) 22 (18) 58 (20) 25 (12)
Often, Very Often 26 ( 7) 15(13)____________________19 ( 7) 22(11)_____________
'Fisher's Exact Test 2-sided p-vaiue
"Excludes 4 women who did not have surgery. The types of surgeries were grouped into 2 categories
which were lumpectomy and mastectomy. Lumpectomy included partial mastectomy, nipple resection, lumpectomy,
re-excision of biopsy, wedge resection, quadrantectomy, segmental mastectomy, and tylectomy. Mastectomy included
subcutaneous mastectomy, total simple mastectomy, modified radical mastectomy, radical mastectomy,
and extended radial mastectomy
to
4 * .
Table 8. Frequency with which women experienced symptoms In arm(s) in the
past 3 months: By Race_________________________________________________
African-
All women Americans
n {%) n {%)
Caucasians
n f%) P-value®
Pins and Needles
Never, Rare 365 (74) 154 (69) 211 (78) 0.05
Sometime 81 (16) 46 (21) 35 (13)
Often, Very Often 49 (10) 24 (11) 25 { 9)
Numbness
Never, Rats 285 (57) 132 (59) 153 (56) 0.0079
Sometime 72(15) 42 (19) 30 (11)
Often, Very Often 138 (28) 50 (22) 88 (32)
Skin Sensitivity
Never, Rare 379 (77) 160 (71) 219(81) 0.04
Sometime 67 (14) 39 (17) 28 (10)
Often, Very Often 49(10) 25(11) 24 ( 9)
Swelling
Never, Rare 389 (79) 163 (73) 226 (83) 0.02
Sometime 51 (10) 29 (13) 22 ( 8)
Often, Very Often 55 (11) 32 (14) 23 ( 8)
Tenderness
Never, Rare 346 (70) 150(67) 196 (72) 0.44
Sometime 95 (19) 48 (21) 47(17)
Often, Very Often 54(11) 26 (12) 28(10)
Tightness
Never, Rare 345 (70) 154 (69) 191 (70) 0.36
Sometime 81 (16) 42(19) 39(14)
Often, Very Often 69(14) 28 (13) 41 (15)
Pain
Never, Rare 382 (77) 170 (76) 212 (78) 0.80
Sometime 73 (15) 34 (15) 39 (14)
Often, Very Often 40 ( 8) 20 ( 9) 20 ( 7)
‘Fisher’ s Exact 2-sided p-vaiue
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Table 9. Frequency with which women experienced symptoms in the arm(s) in the past 3 months according
to lymphedema status and type of surgery _________________________________ ______________________________
Lymphedema p-value* Type of Surgery** p-value*
No Yes Lumpectomy Mastectomy
n <% ) n (% ) n (% ) n (% )
Pins and Needles
Never, Rare 290 (77) 75 (63) 0.001 225 (79) 136(66) 0.009
Sometime 58 (15) 23 (19) 37 (13) 44(21)
Often, Very Often 27 ( 7) 22 (18) 24 ( 8) 25 (12)
Numbness
Never, Rare 242 (65) 43 (36) <.00001 174(61) 107 (52) 0.15
Sometime 47(13) 25 (21) 40 (14) 32 (16)
Often, Very Often 86 (23) 52 (43) 72 (25) 66 (32)
Skin Sensitivity
Never, Rare 304 (81) 75 (63) 0.0002 230 (80) 145(71) 0.05
Sometime 43 (11) 24 (20) . 33 (12) 34(17)
Often, Very Often 28 ( 7) 21 (18) 23 ( 8) 26 (13)
Swelling
Never, Rare 347 (93) 42 (35) <.00001 236 (83) 149 (73) 0.03
Sometime 17(5) 34 (28) 25 ( 9) 26 (13)
Often, Very Often 11(3) 44 (37) 25( 9) 30 (15)
Tenderness
Never, Rare 280 (75) 66 (55) 0.00002 202 (71) 141 (69) 0.83
Sometime 67 (18) 28 (23) 52 (18) 42 (20)
Often, Very Often 28 ( 7) 26 (22) 32(11) 22(11)
Tightness
Never, Rare 281 (75) 64 (53) 0.00004 206 (72) 135 (66) 0.04
Sometime 53 (14) 28 (23) 37(13) 44 (21)
Often, Very Often 41 (11) 28 (23) 43(15) 26 (13)
O N
Table 9. Frequency with which women experienced symptoms in the arm(s) in the past 3 months according
to lymphedema status and type of surgery - Continued_______________________________________________
Pain
Never, Rare
Sometime
Often, Very Often
‘Fisher's Exact Test 2-sided p-value
“ Excludes 4 women who did not have surgery. The types of surgeries were grouped into 2 categories
which were lumpectomy and mastectomy. Lumpectomy included partial mastectomy, nipple resection, lumpectomy,
re-excision of biopsy, wedge resection, quadrantectomy, segmental mastectomy, and tylectomy. Mastectomy included
subcutaneous mastectomy, total simple mastectomy, modified radical mastectomy, radical mastectomy,
and extended radial mastectomy
308(82) 74(62) 0.00003 221 (77) 157(77) 0.28
45 (12) 28 (23) 46(16) 27 (13)
22 ( 6) 18(15) 19 ( 7) 21 (10)
Table 10, Overall fatigue mean score by age, stage of
disease, and lymphedema status (number and percent]
Overall fatigue mean score** p-value*
Low Moderate High
n (% } n {%) n {% )
Age at diagnosis
35-44 75 (27) 49 (31) 16 (28) 0.67
45-54 107 (38) 50 (32) 23 (40)
55-64 100 (35) 57 (37) 18 (32)
Stage of disease
Insitu 52(18} 35 (22) 12 (21) 0.59
invasive 230 (82) 121 (78) 45 (79)
Lymphedema status
Caucasians
No 124 (58) 64 (30) 25 (12) 0.22
Yes 27 (47) 24 (41) 7(12)
African-Americans
No 98 (60) 46 (28) 18(11) 0.52
Yes 33 (53) 22 (35) 7(11)
■"Fisher's Exact Test 2-sided p-value
**Low score: 0-3.9; Moderate score: 4.0-6.9; High score: 7.0-10
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Table 11. Adjusted odds ratios of lymphedema status
95%
# lymphedema / # Adjusted Confidence
Characteristics no lymphedema Odds Ratio* Interval
Age fyrs)
3 5 -4 4 39/101 1.0
4 5 -5 4 50/130 1.10 0.65- 1.89
55 - 64 31 /144 0.56 0.31 - 1.02
Race
Whites 58/213 1.0
African-Americans 6 2/ 162 1.14 0.73- 1.79
BM I (kg/m2)**
<25 45/211 1.0
25 - 27.9 31 /7 5 2.18 1.26-3.79
28-29.9 13/33 2.18 1.04-4.57
30+ 30 / 55 2.72 1.50 - 4.96
Trend p = <.0001
Chemotherapy
No 55/244 1.0
Yes 65/131 1.9 1.18-3.06
Tamoxifen
No 54/ 172 1.0
Yes 66/203 0.97 0.53-1.50
Surgery***
Lumpectomy 6 7 /219 1.0
Mastectomy 53/152 0.97 0.57- 1.67
Radiation
No 64/212 1.0
Yes________________________ 56/163____________1.13 0.66- 1.93__________
* Adjusted for age, race, BM I, chemotherapy status, tamoxifen status, type of surgery,
and radiation status
**BM I data missing for one respondent
***ExcIud®s 4 women who did not have surgery. The types of surgeries were grouped
into 2 categories which were lumpectomy and mastectomy. Lumpectomy included
partial mastectomy, nipple resection, re-excision of biopsy, wedge resection,
quadrantectomy, segmental mastectomy, and tyfectomy.
Mastectomy included subcutaneous mastectomy, total simple mastectomy,
modified radical mastectomy, radical mastectomy, and extended radial mastectomy.
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30
The impact of chemotherapy on risk of lymphedema differed among those
less than 55 years and those 55 years of age and older (Table 12). BMI was a risk
factor for lymphedema in both age groups.
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31
Table 12. Adjusted odds ratios of lymphedema status stratified by age
Characteristics
Women under 55
Race
Whites
African-Americans
Adjusted 95%
# lymphedema I Odds Confidence
#mo lymphedema Ratio* Interval
43 /132
4 8 / 99
1 ,0
1.22 0.72 - 2.08
BMI (kg/m )**
<25
25 - 27.9
28 - 29.9
30+
Trend p = 0.0002
37 /148
2 3 / 41
9 / 15
2 0 /2 6
1.0
2.30
2.71
2.91
1.21 -4.38
1.05-6.97
1.41 -6.00
Chemotherapy
No
Yes
40 /127
49/104
1.0
1.36 0.79 - 2.34
Surgery***
Lumpectomy
Mastectomy
49/131
40/ 97
1.0
1.13 0.60-2.11
Radiation
No
Yes
46/132
4 3 / 99
1.0
1.46 0.78 - 2.73
Tamoxifen
No
Yes
41 /112
48/119
1.0
1.02 0.61 - 1.71
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Table 12. Adjusted multivariate model of lymphedema status stratified
by age - Continued
Characteristics
# lymphedema /
# no lymphedema
Adjusted
Odds
Ratio
95%
Confidence
Interval
Women 55 and over
Race
Whites 15/81 1.0
African-Americans 16 / 63 0.91 0.37 - 2.27
BM I (kg/m2) **
<25 8 /6 3 1.0
25 - 27.9 8/34 1.68 0.54 - 5.23
28 - 29.9 5 /1 8 1.88 0.50 - 7.09
30+ 10/29 2.53 0.79-8.10
Trend p = 0.05
Chemotherapy
No 15/117 1.0
Yes 16/ 27 5.68 2.18-14.81
Surgery***
Lumpectomy 18/88 1.0
Mastectomy 13/55 0.43 0.13-1.41
Radiation
No 18/80 1.0
Yes 13/64 0.58 0.20- 1.71
Tamoxifen
No 13/60 1.0
Yes 18/84 0.79 0.33 - 1.89
* Adjusted for age, race, BM I, chemotherapy status, tamoxifen status, type of
surgery, and radiation status
**BM I data missing for one respondent
***Excludes 4 women who did not have surgery. The types of surgeries were
grouped into 2 categories which were lumpectomy and mastectomy.
Lumpectomy included partial mastectomy, nipple resection,
re-excision of biopsy, wedge resection, quadrantectomy, segmental mastectomy,
and tylectomy. Mastectomy included subcutaneous mastectomy, total simple
mastectomy, modified radical mastectomy, radical mastectomy, and extended
radial mastectomy.
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33
CHAPTER V - DISCUSSION
Experiencing the sensation of pins and needles, skin sensitivity, swelling, and
tightness were strong indicators for the presence of lymphedema. This condition has
been known to have a negative affect on a woman’s quality of life by limiting her
physical and social activities.
In a study conducted by Pezner and his colleagues, age at diagnosis of breast
cancer was the most important factor predicting arm lymphedema (7). They found
that patients 60 years of age and older were at greater risk of lymphedema than those
younger than 60 (p < 0.02). However, in our study, which was limited to women
between the ages of 35 and 64 years at diagnosis, we find that women younger than
55 years have a greater risk of lymphedema than older women. In both age groups,
body mass index was a strong predictor of lymphadema. In a prior study conducted
by Say et ai. (5), body weight categorized as 100 pounds or less (6.5%), 101 - 200
pounds (78.7%), and 200 pounds or greater (5.9%) was associated with the
development of lymphadema. One shortcoming of this earlier paper is that 107
patients were missing data on weight.
Overall we also found that chemotherapy was associated with lymphadema.
However, in our age stratified analysis, chemotherapy was not associated with
lymphedema among women under age 55 years. Although earlier studies have
reported a greater frequency of lymphedema in women who have received pre or
post-operative radiation (5), our results were inconsistent with such findings.
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34
No evidence exists to demonstrate that lymphadema treatments are effective
in reducing swelling or curing the condition. In one study, coiimarin, an
anticoagulant was found to be effective in treating women with lymphedema. When
a study was performed to replicate those findings, coumarin was found to be
ineffective in managing lymphedema and surprisingly coumarin-related hepatotoxic
effects were observed among the treated women (8).
The present study shows that 28% of African-Americans and 21% of
Caucasians experienced arm lymphedema following their breast cancer diagnoses.
No prior study has reported the prevalence of this condition among African
American women. Beaulac et al. (9) have reported that lymphadema strongly
impacted the quality of life of a group of non-white patients (African-American,
Hispanic, Asian, and Middle Eastern) but did not report data separately for the
individual ethnic subgroups in their study. Given that nearly 30% of African
American -women with early stage breast cancer experienced lymphedema following
diagnosis, it is important that an effort is made by physicians to counsel their patients
about the possibility of developing the condition following treatment.
In our study, a higher proportion of African-Americans than Caucasians
reported that treatments used to manage their lymphedema were ineffective. No
African American patients experienced a resolution of their lymphadema, although a
few Caucasian patients did. Furthermore, African-Americans, tended to experience
pins and needles sensations and skin sensitivity in the chest wall more frequently and
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
35
more intensely than Caucasians in the 3 months prior to interview, whereas
Caucasian women were more likely to report numbness. Their experience of other
chest wall symptoms was similar between the two groups of patients. Our study has
several limitations. Our treatment information is restricted to the patient’s first six
months of treatment (chemotherapy and radiation treatments). Although we queried
women about subsequent surgeries that they may have had for reconstruction
purposes, we did not document treatments that they may have received for
recurrence or progression of their breast cancer. In addition, we relied on patients’
self- reports of tamoxifen treatment. Further, we did not collect information on when
the lymphadema developed among these patients. Nevertheless, our study is unique
because it provides an estimate of the impact of lymphedema on both African-
American and Caucasian women, identifies body mass index as an important
predictor of this condition and also suggests that chemotherapy treatment of older
women may contribute to the development of lymphedema as well. It also
demonstrates that the arm and chest wall symptom complex experienced by African
American and Caucasian women differs. Given that nearly 30% of African
American women, with early stage breast cancer may experience lymphedema
following diagnosis, and that their symptom experience wall differ from that of
Caucasian women, it is important that physicians are aware of their symptoms and
that an effort is made by physicians to counsel their patients about the possibility of
developing the condition following treatment.
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36
REFERENCE
Beaulac S, McNair L, Scott T et al. Lymphedema and Quality of Life in Survivors of
Eariy-Stage Breast Cancer. Arch Surg 2002; 137:1253-1257.
Erickson V, Pearson M, Ganz P, et al. Arm Edema in. Breast Cancer Patients. Journal of
the National Cancer Institute 2G01;93(2):96~111.
Ganz, P. The Quality of Life after Breast Cancer - Solving the Problem of Lymphedema.
The New England Journal of Medicine 1999; 340(5):383-385.
Kwan W, Jackson J, Weir L et al. Chronic Arm Morbidity After Curative Breast Cancer
Treatment: Prevalence and Impact on Quality of Life. Journal of Clinical Oncology .
2002;20(20):4242-4248.
Loprinzi C, Kugler J, Sloan J et al. Lack of Effect of Coumarin in Women with
Lymphedema after Treatment for Breast Cancer. The New England Journal of Medicine
1999;340(5):346-350.
Mirolo B, Bonce I, Chapman M et al. Psychosocial benefits of postmastectomy
lymphedema therapy. Cancer Nursing 1995; 18(3): 197-205.
Pezner R, Patterson M, Hill R et al. Arm Lymphedema In Patients Treated Conservatively
For Breast Cancer: Relationship To Patients Age And Axillary Node Dissection Technique.
Int. J. Radiation Oncology Biol Phys 1986;12:2079-2083.
Piper B, Kibble S, Dodd M et al. The Revised Piper Fatigue Scale: Psycometric Evaluation
in Women with Breast Cancer. Piper 1998;25(4):677-684.
Price J, Purtell J. Prevention and Treatment of Lymphedema After Breast Cancer. The
American Journal of Nursing 1997; 97(9):34-37.
Samarel N, Fawcett J, Krippendorf K et al. Women’s perceptions of group support and
adaptation to breast cancer. Journal o f Advanced Nursing 1998;28(6): 1259-1268.
Say C, Donegan W. A Biostatistlcal Evaluation of Complications From Mastectomy.
Surgery, Gynecology, and Obstetrics 1974;138:370-375.
Velanovich Vic, Szymanski W. Quality of Life of Breast Cancer Patients with
Lymphedema. The American Journal of Surgery 1999;177(3):184-187.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
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Carraway, La Creachia
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Lymphedema: Impact on breast cancer survivors
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Applied Biostatistics and Epidemiology
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