Upper-Extremity Deep Vein Thrombosis in Patients With Breast Cancer With Chest Versus Arm Central Venous Port Catheters

Abstract

Most of the patients undergoing treatment for cancer require placement of a totally implantable venous access device to facilitate safe delivery of chemotherapy. However, implantable ports also increase the risk of deep vein thrombosis and related complications in this high-risk population. The objective of this study was to assess the incidence of upper-extremity deep vein thrombosis (UEDVT) in patients with breast cancer to determine whether the risk of UEDVT was higher with chest versus arm ports, as well as to determine the importance of previously reported risk factors predisposing to UEDVT in the setting of active cancer. We retrospectively reviewed the medical records of 297 women with breast cancer who had ports placed in our institution between the dates of December 1, 2010, and December 31, 2016. The primary outcome was the development of radiologically confirmed UEDVT ipsilateral to the implanted port. Overall, 17 of 297 study subjects (5.7%) were found to have UEDVT. There was 1 documented case of associated pulmonary embolism. Fourteen (9.5%) of 147 subjects with arm ports experienced UEDVT compared with only 3 (2.0%) of 150 subjects with chest ports (P = .0056). Thus, implantation of arm ports as opposed to chest ports may be associated with a higher rate of UEDVT in patients with breast cancer.

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Breast Cancer: Basic and Clinical Research
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DOI: 10.1177/1178223418771909
Introduction
It is estimated that more than 230 000 women living in the
United States were diagnosed with breast cancer in 2015,1
and 1 in 8 women in the United States will be diagnosed
with breast cancer during her lifetime. Despite the
increased incidence, outcomes for breast cancer survivors
are improving at unprecedented rates with improved
screening, targeted chemotherapy regimens, and stringent
surveillance guidelines. We are better equipped to fight
malignancy, but a diagnosis of cancer remains associated
with a myriad of complications. Most standard chemother-
apy regimens include drugs that are vesicants, and although
they are effective in killing cancer cells, they are also toxic
to local tissues if extravasation occurs. Consequently, the
route by which these drugs are delivered is critical. These
medications must be effectively delivered into the systemic
circulation without causing damage to the surrounding tis-
sues, a requirement that is satisfied by totally implanted
venous access ports. Despite multiple attempts to deliver
chemotherapy through peripheral intravenous catheters,
up to 44% of patients with breast cancer over the age of
66 years receive a port to administer their chemotherapy,
and patients who are younger or those who need an
extended course of treatment are even more likely to
undergo port placement.2 Historically, chemotherapy ports
have been implanted into the chest wall via the subclavian
or internal jugular (IJ) veins, but upper-extremity access
has become a popular choice in recent years. Various argu-
ments in support of upper-extremity port placement
include that arm ports are more cosmetically appealing,
allow easier access, and may be medically indicated in cer-
tain patient populations.3–6 In our institution, many
patients elect to undergo breast reconstruction after com-
pletion of their treatment, and arm ports have been
embraced for removing the port from the reconstruction
field, thus minimizing the risk for surgical complications.
However, despite the popularity of arm port placement,
there has been research that suggests that the risk of cath-
eter-related upper-extremity deep vein thrombosis
(UEDVT) may be increased in patients with arm ports as
opposed to chest ports. Our goal was to determine whether
there is a difference in incidence of catheter-related
UEDVT in arm ports versus chest ports, as well as to
investigate the contribution of previously identified risk
factors for clot formation.
Upper-Extremity Deep Vein Thrombosis in Patients
With Breast Cancer With Chest Versus Arm Central
Venous Port Catheters
Danielle Tippit1, Eric Siegel2, Daniella Ochoa3, Angela Pennisi4,
Erica Hill3, Amelia Merrill3, Mark Rowe3, Ronda Henry-Tillman3,
Aneesha Ananthula1 and Issam Makhoul4
1Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR,
USA. 2Fay W. Boozman College of Public Health, Universit y of Arkansas for Medical Sciences,
Little Rock, AR, USA. 3Division of Breast Surgical Oncology, Department of Surgery, University of
Arkansas for Medical Sciences, Little Rock, AR, USA. 4Division of Medical Oncology, Department
of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
ABSTRACT: Most of the patients undergoing treatment for cancer require placement of a totally implantable venous access device to facilitate
safe delivery of chemotherapy. However, implantable ports also increase the risk of deep vein thrombosis and related complications in this high-
risk population. The objective of this study was to assess the incidence of upper-extremity deep vein thrombosis (UEDVT) in patients with breast
cancer to determine whether the risk of UEDVT was higher with chest versus arm ports, as well as to determine the importance of previously
reported risk factors predisposing to UEDVT in the setting of active cancer. We retrospectively reviewed the medical records of 297 women with
breast cancer who had ports placed in our institution between the dates of December 1, 2010, and December 31, 2016. The primary outcome
was the development of radiologically confirmed UEDVT ipsilateral to the implanted port. Overall, 17 of 297 study subjects (5.7%) were found to
have UEDVT. There was 1 documented case of associated pulmonary embolism. Fourteen (9.5%) of 147 subjects with arm ports experienced
UEDVT compared with only 3 (2.0%) of 150 subjects with chest ports (P = .0056). Thus, implantation of arm ports as opposed to chest ports may
be associated with a higher rate of UEDVT in patients with breast cancer.
KEYWORDS: Upper extremity deep venous thrombosis, breast cancer, chemotherapy, central venous port catheter
RECEIVED: Septembe r 30, 2017. ACCEPTED: March 2 9, 2018.
TYPE: Original Research
FUNDING: The author(s) di sclose d receip t of the foll owing na ncial su pport fo r the
research, authorship, and/or publication of this article: This research was partially funded
by the Laur a F. Hutchins, M. D. Disting uished C hair for Hem atology a nd Onco logy.
DECLARATION OF CONFLICTING INTERESTS: The author(s) dec lared no po tential
conic ts of inter est with re spect to t he resear ch, autho rship, an d/or publ icatio n of this
article.
CORRESPONDING AUTHOR: Issam Makh oul, Divi sion of Me dical O ncolog y, Departm ent
of Interna l Medic ine, Univer sity of Arkansa s for Medic al Scie nces, 43 01 West Mark ham,
Littl e Rock, AR 72 205, USA . Email: mak houliss am@uams.edu
771909BCB0010.1177/1178223418771909Breast Cancer: Basic and Clinical ResearchTippit et al
research-article2018

2 Breast Cancer: Basic and Clinical Research
Methods
Study design and patient selection
The study protocol was evaluated by the institutional review
board and determined to be low-risk research and therefore not
requiring patient consent. We retrospectively reviewed our
electronic medical record system to identify patients with a
diagnosis of breast cancer who underwent port placement at
this institution during the 6-year period from December 1,
2010, to November 30, 2016. We identified a total of 297
women ≥18 years of age with a histologically confirmed diag-
nosis of breast cancer who underwent port placement during
this time period. The data set was further analyzed to identify
patients who reported symptoms commonly associated with
UEDVT including upper limb edema, pain, and erythema.
Patient charts were used to follow patients for UEDVT from
time of port placement to time of port removal, patient death,
or January 1, 2017.
Upper-extremity deep vein thrombosis was defined as a
UEDVT ipsilateral to the patient’s port that was confirmed by
Doppler ultrasound or other comparable radiologic studies.
Due to both the retrospective nature of our study and the fact
that venous Doppler is not a routine test, only patients with
clinically symptomatic DVTs were included in this study. Our
study was not designed to evaluate the incidence of asympto-
matic catheter-related UEDVT. For all 297 patients, informa-
tion was collected regarding patient age, sex, race, and medical
history including oncologic history. Patient charts were also
assessed for known risk factors for clot formation including
personal history of deep vein thrombosis (DVT), personal or
family history of clotting disorder, tobacco use, alcohol use,
obesity, recent surgery, immobility, and chronic illness (ie, heart
failure, chronic kidney disease). Advanced analysis was not
done for several known risk factors for clot formation includ-
ing personal history of DVT, family history of clotting disorder,
chronic disease, and recent surgery for the following reasons:
only 2 patients had a personal history of DVT and neither of
these patients developed a UEDVT associated with their port.
No patients reported a family history of clotting disorder. At
the time of port placement, none of the patients in this study
had significant comorbidities such as chronic kidney disease or
heart failure. All patients underwent surgery either during the
time of port placement or 3 months prior, so this particular risk
factor was present for all patients in this study.
Statistical analysis
In addition to port placement and UEDVT occurrence, factors
collected for analysis consisted of patient demographics (age,
race, body mass index [BMI], and self-reported use of alcohol
and tobacco), tumor characteristics (breast cancer sidedness,
histopathology, American Joint Committee on Cancer [AJCC]
stage, and hormone receptor status), and treatment factors
(chemo setting, radiotherapy, operator, port placement
sidedness, vein, and catheter size). These factors were assessed
for imbalance between patients with ports placed in the arm
versus the chest using the Kruskal-Wallis test for continuous
factors and Fisher exact test for both binary and multinomial
categorical factors, except for operator and vein, which were
imbalanced by design. To conduct analysis for risk of UEDVT,
all factors not already binary were dichotomized, so that every
factor examined would consist of 2 groups. Age was dichoto-
mized as 54 and younger versus 55 and older. The BMI was
dichotomized as under 30 (nonobese) versus 30 or more
(obese). Histopathology was dichotomized as invasive ductal
carcinoma versus all other histopathologies. The AJCC stage
was dichotomized 2 different ways, first as stage IV (meta-
static) versus stages I to III (nonmetastatic) and then as stage I
(very early) versus stages II to IV (more advanced). Chemo set-
ting was dichotomized as adjuvant chemotherapy versus all
other settings. Breast cancer sidedness and vein could not be
dichotomized sensibly and were excluded from risk analysis.
Risk analysis then proceeded as follows. In the 2 groups of each
factor, the UEDVT rate was computed as the number of sub-
jects who experienced DVT divided by the number of subjects
at risk for DVT. Then, the factor’s relative risk between groups
was estimated as the ratio of its UEDVT rates, whereas the
standard error of this ratio was used to estimate a Wald 95%
confidence interval (95% CI). Finally, Fisher exact test was
used to assess significance of the estimated risk ratios. Because
of the small number of DVTs, multivariate analysis was not
conducted to avoid overfitting and consequent spurious results.
All tests were 2-sided. All P values are reported numerically
and interpreted for significance using the sliding-scale
approach of Mendenhall etal7 as follows: P < .01 is “highly sig-
nificant,” .01 < P < .05 is “statistically significant,” .05 < P < .10 is
“trending towards significant,” and P > .10 is “not significant.”
Results
Of the 988 patients with breast cancer seen in our institution
during the 6-year study period, the number of patients who
had a port placed for administration of chemotherapy was 297
(30%), which represents the total study population and is not
significantly different from other institutions.2 We looked at a
total of 147 patients with arm ports and 150 patients with
chest ports. Among those who had chest ports, 82 (54.7%)
were left sided and 68 (45.3%) were right sided. Among those
with arm ports, 75 (51.0%) were left sided and 72 (49.0%) were
right sided.
The demographic characteristics of all patients included in
this study are presented in Table 1. Mean age was 55 years
(range: 26-77 years). Of 297 patients, 212 were European
American (EA) and 85 were African American (AA). The
incidence of breast cancer in EA women in Arkansas is esti-
mated to be 107.7 per 100 000 women, whereas the incidence
in AA women is estimated to be 106.1.1 Although our data set
includes a greater number of EA women, we believe that this
difference is likely due to differences related to access to health

Tippit et al 3
Table 1. Patient and tumor characteristics by port placement.
PATIENT/TUMOR CHARACTERISTIC ALL SUBJECTS (N = 297) ARM (N = 147) CHEST (N = 150) P VALUEa
Age, y .85b
Median 55 54 56
Interquartile range 45-62 46-62 45-63
Range 26 -77 26 -75 27-77
Race, No. (%)c.31
African American 85 (28.6) 38 (25.9) 47 (31.3)
European American 212 ( 71.4) 10 9 (74.1) 103 (68.7)
BMI, kg/m2.42b
Median 29.4 29.2 29.7
Interquartile range 25 .1-34. 2 24.1-34.9 26.3-33.9
Range 17.4-51.9 17.4-51.9 19 .1 - 47. 8
Alcohol use, No. (%)c.071
No 213 ( 71.7 ) 98 (6 6.7) 115 ( 76. 7 )
Yes 84 (28.3) 49 (33.3) 35 (23.3)
Tobacco use, No. (%)c.76
No 243 (81.8) 119 (81.0) 124 (82.7)
Yes 54 (18. 2) 28 (19.0) 26 (17. 3)
Cancer sidedness, No. (%)c.62
Left side 14 0 (47.1) 73 (4 9.7) 67 (4 4.7)
Right side 148 (49.8) 70 (47.6) 78 (52.0)
Bilateral 4 (1.3) 1 (0.7) 3 (2.0)
No primary 5 (1.7 ) 3 (2.0) 2 (1. 3)
Cancer pathology, No. (%)c.59
Invasive ductal 270 (90.9) 134 (91.2) 136 (90 .7)
Invasive lobular 2 2 ( 7. 4) 9 (6.1) 13 (8.7)
Metaplastic 3 (1.0) 2 (1.4) 1 (0.7)
Neuroendocrine 1 (0.3) 1 (0.7 ) 0 (0.0)
Squamous cell 1 (0.3) 1 (0.7 ) 0 (0.0)
AJCC stage, No. (%)c.88
I 48 (16. 2) 23 (15.6) 25 (16.7)
II 14 0 (47.1) 68 (4 6. 3) 72 (48.0)
III 57 (19.2) 31 ( 21.1) 26 ( 17. 3 )
IV 52 ( 17. 5) 25 (17.0) 27 (18.0)
ER status, No. (%)c.80
Negative 96 (32.3) 49 (33.3) 47 (31.3)
Positive 201 (6 7. 7 ) 98 (66.7) 103 (68.7)
PR status, No. (%)c.64
(Continued)

4 Breast Cancer: Basic and Clinical Research
PATIENT/TUMOR CHARACTERISTIC ALL SUBJECTS (N = 297) ARM (N = 147) CHEST (N = 150) P VALUEa
Negative 12 9 (43.4) 6 6 (44.9) 63 (42.0)
Positive 168 (56.6) 81 ( 5 5 .1) 87 (58.0)
HER2/Neu status, No. (%)c.70
Negative 210 (70.7 ) 10 2 (6 9.4) 108 (72.0)
Positive 87 (29.3) 45 (30.6) 42 (28.0)
Triple-negative disease, No. (%)c.78
No 22 9 ( 7 7.1) 112 (7 6 . 2 ) 117 (78.0)
Yes 68 (22 .9) 35 (23.8) 33 (22.0)
Abbreviations: AJCC, American Joint Committee on Cancer; BMI, body mass index; ER, estrogen receptor; PR, progesterone receptor.
aP values are from either Fisher exact tests.
bWilcoxon rank sum tests.
cNumber (percent of subjects in group).
Table 1. (Continued)
care in our state. The median BMI was 29.4 (range: 17.4-51.9).
In all, 54 patients were current cigarette smokers and 84
patients reported alcohol use. There was no statistically signifi-
cant difference between the arm and chest port groups regard-
ing age, race, BMI, or tobacco use. However, the percentage
reporting alcohol use was 10 points higher with arm ports
(33.3%) compared with chest ports (23.3%), and the difference
trended toward significance (P = .071; see Table 1).
Tumor characteristics for all 297 patients were compared for
differences with port placement using Fisher exact test, and the
results are found in Table 1. In all, 140 patients had a left-sided
tumor, 148 patients had a right-sided tumor, 4 patients had
bilateral breast masses, and 5 patients had no breast primary as
they were diagnosed with recurrent metastatic disease. More
than 90% of patients (270) were diagnosed with invasive ductal
carcinoma. The other observed pathologic types consisted of
invasive lobular carcinoma (22 or 7.4%), metaplastic carcinoma
(3 or 1.0%), neuroendocrine carcinoma (1 or <1%), and squa-
mous cell carcinoma (1 or <1%). In all, 48 patients were diag-
nosed with stage I disease, 140 with stage II disease, 57 with
stage III disease, and 52 with stage IV disease. About 201
tumors were estrogen receptor (ER) positive and 96 were nega-
tive; 168 tumors were progesterone receptor (PR) positive and
129 were negative; 87 tumors were HER2/Neu positive and
210 were negative; and 68 patients had triple-negative disease.
No significant differences were seen in tumor laterality, pathol-
ogy, stage, ER status, PR status, or HER2/Neu status between
patients with chest ports and those with arm ports (Table 1).
Treatment-related factors were analyzed using Fisher exact
test and the results are presented in Table 2. Ports were placed
for adjuvant chemotherapy in 89 patients, for neoadjuvant
chemotherapy in 154 patients, and for palliative chemotherapy
in 52 patients; 2 patients had ports placed but did not receive
chemotherapy. Radiation therapy was given to 113 patients,
whereas 184 patients did not have radiation. In all, 256 ports
were placed by breast surgery and 41 ports were placed by
interventional radiology. At our institution, interventional
radiology does not place arm ports, so all 147 arm ports were
placed by breast surgery. About 157 ports were left sided and
140 were right sided. For chest port catheters, 6 were placed in
the axillary vein, 48 were placed in the IJ vein, and 99 were
placed in the subclavian vein. For arm port catheters, 99 were
placed in the basilic vein, 36 were placed in the brachial vein,
and 2 were placed in the cephalic vein. Seven operative reports
did not specify the vein of catheter entry. The catheter size was
only recorded for 176 of the 297 total ports placed. The mean
catheter size for all patients with nonmissing data was 5.5 F
(range: 4-8 F). No statistically significant differences were seen
in chemotherapy setting, radiation therapy, or port laterality
between patients with arm ports and chest ports. There was a
highly significant difference in venous catheter size between
the 2 groups (P < .0001), with an average size of 5.0 F (range:
5-8 F) for arm ports and 6.2 F (range: 4-8 F) in chest ports
(Table 2). Of the 297 catheters placed, 296 were removed by
the follow-up cutoff date of January 1, 2017. The number of
days the patient’s catheter was in place had a median (range) of
556 (10-2182) overall, 473 (11-2182) for arm ports, and 661
(10-2186) for chest ports; means and totals are shown in Table
2. Similarly, the number of days of follow-up for UEDVT had
a median (range) of 539 (3-2186) overall, 452 (3-2182) for arm
ports, and 661 (7-2186) for chest ports; means and totals are
also shown in Table 2.
Figure 1 shows Kaplan-Meier curves for the time in days
from port placement to UEDVT development. Among the
150 subjects with chest ports, the 3 UEDVTs occurred at 7, 48,
and 124 days after the port placement. Among the 147 subjects
with arm ports, the first 10 UEDVTs occurred by the 48th day
after the port was placed, whereas the 11th, 12th, 13th, and
14th UEDVTs occurred at 68, 90, 98, and 267 days after port
placement, respectively. In neither group did a UEDVT occur

Tippit et al 5
Table 2. Cancer treatment factors by port placement.
TREATMENT FACTOR ALL SUBJECTS (N = 297) ARM (N = 147) CHEST (N = 150) P VALUEA
Chemo setting, No. (%)b.13
Adjuvant 89 (30.0) 36 (24.5) 53 (35.3)
Neoadjuvant 154 (51.9) 85 (57.8) 69 (46.0)
Palliative 52 ( 17. 5) 25 (17.0) 27 (18.0)
None 2 (0.7) 1 (0.7) 1 (0.7)
Radiotherapy, No. (%)b1. 00
No 184 (62.0) 91 (61.9) 93 (62.0)
Yes 113 (38.0) 56 (3 8 .1) 57 (38.0)
Operator, No. (%)b—c
IR 41 (13 . 8) 0 (0.0) 41 (27.3)
Surgery 256 (8 6.2) 147 (100.0) 109 (72.7)
Port side, No. (%)b.56
Left 157 (52. 9) 75 (51.0) 8 2 (54.7)
Right 14 0 (4 7.1) 72 (49.0) 68 (45.3)
Vein, No. (%)d—c
Basilic 99 (3 4 .1) 99 ( 70.7) 0 (0.0)
Brachial 36 (12.4) 36 (25.7) 0 (0.0)
Cephalic 2 (0.7) 2 (1.4) 0 (0.0)
Axillary 6 ( 2 .1) 3 (2 .1) 3 (2.0)
IJ 48 (16.6) 0 (0.0) 48 (32.0)
Subclavian 9 9 (3 4 .1) 0 (0.0) 99 (66.0)
(Not recorded) (7) (7) (0)
Catheter size, F <.0001e
No. (%) nonmissing 176 (5 9. 3) 11 0 ( 74 . 8) 66 (4 4. 0)
Mean (SD) 5 . 5 (1.1) 5.0 (0.3) 6. 2 (1.1)
Range 4.0-8.0 5.0-8.0 4.0-8.0
Days catheterizedf—c
Mean; Median 669.4; 556 512.3; 473 823.4; 661
Range 10- 2182 11 - 218 2 10 -218 6
Total (ie, catheter-days) 198 817 75 302 123 515
Days of follow-up for UEDVTf—c
Mean; median 655.8; 539 487.5; 45 2 820.8; 6 61
Range 3-2186 3-2182 7- 218 6
Total (ie, person-days) 194 785 71 659 123 126
Abbreviations: IJ, internal jugular; UEDVT, upper-extremity deep vein thrombosis, IR, interventional radiology.
aP values are from Fisher exact tests.
bNumber (percent of number in group).
cUnless not tested.
dNumber (percent of number nonmissing in group).
eWilcoxon rank sum tests.
fDays were calculated using January 1, 2017, as the date when follow-up ended for UEDVT development and catheter removal. One catheter out of 297 remained in place
on this date.

6 Breast Cancer: Basic and Clinical Research
more than 365 days after port placement. All UEDVTs were
therefore included in subsequent analysis.
Table 3 shows that the symptomatic UEDVT rate was
almost 5 times higher in patients with arm ports compared
with patients with chest ports (relative risk = 4.76 with 95% CI
of 1.40-16.23), and that the difference was highly significant
(P = .0056). Table 3 also indicates that ports placed on the
patient’s left side were associated with a 63% decrease in
UEDVT rate (relative risk = 0.37 with 95% CI of 0.13-1.03),
but this difference only trended toward significance (P = .071).
Finally, Table 3 suggests that there was no statistically signifi-
cant risk of UEDVT associated with age, obesity, race, alcohol
use, tobacco use, histopathology, metastatic disease, ER/PR/
HER2 positivity, triple-negative disease, chemotherapy setting,
radiation therapy, or operator.
Discussion
Malignancy alone is a well-established risk factor for hyperco-
agulability and deep venous thrombosis. In addition, many
patients with cancer are relatively immobile due to advanced
disease or debilitating side effects of treatment, further increas-
ing their risk for clot formation. Other factors shown to
increase the risk for DVT specifically in patients with cancer
include thrombocytosis, anemia, leukocytosis, male sex, factor
V Leiden mutation, mechanical factors (eg, port insertion
technique, and port revisions), certain types of cancer, meta-
static disease, and certain chemotherapy drugs.8–12 In this study
of 297 patients with breast cancer who underwent port place-
ment over a period of 6 years, there was a highly significant
difference in catheter-related UEDVT in patients who received
arm ports as opposed to those who received chest ports, with
the incidence of catheter-related thrombosis being higher with
arm ports. Given that most patients who developed UEDVT
had an excellent baseline performance status, we expect that
the risk for clot formation and increased morbidity may be
even higher in patients who are less healthy. These results could
offer guidance regarding the safest option for port placement
in each individual patient depending on specific patient attrib-
utes, comorbidities, and risk factors.
Of the patients who developed UEDVT during this time
period, almost 5 times as many had arm ports despite the total
number of patients with arm ports being almost equal to those
with chest ports. This increased incidence could be due to the
smaller diameter of upper-extremity veins, as it is hypothesized
that when the catheter takes up more than 50% of the vessel
lumen, there is an increased risk for thrombosis.3 We were una-
ble to collect information about the catheter-to-vein ratio in
this study, but the average vascular catheter size for arm ports
was 5 F versus 6.2 F for chest ports, a statistically significant
difference. However, the veins in the chest are generally larger
and therefore the catheter-to-vein ratio may in fact be smaller
than with arm ports. The increased risk may also be related to
the presence of a longer vascular catheter,13 stress applied with
everyday use when the port pocket is in the forearm and the
vascular catheter crosses the elbow joint, or other factors that
have yet to be determined. Current literature (Table 4) suggests
that the incidence of UEDVT in arm ports is roughly equiva-
lent to that of chest ports for the most part, with an incidence
of 12% to 64% in most retrospective studies and 37% to 66% in
a small number of prospective studies.19 However, most of the
current research is looking at incidence of thrombosis as related
to implantation technique or operator (ie, surgical versus imag-
ing guided, interventional radiology versus surgery) and is
overall more focused on total complications related to port
insertion. We know of only 2 large-scale studies18,20 that spe-
cifically looked at data sets that included both arm and chest
ports to draw a comparison between the two. We did not find
any studies looking at catheter-related UEDVT in patients
with breast cancer alone, but the studies below do involve
oncology patients, some of which have breast cancer.
Furthermore, although the data from the individual studies
looking at one port location are quite variable, it is worth not-
ing that the overall incidence of UEDVT in arm ports is higher
in both studies comparing the 2 directly, a finding corroborated
by the data that we have collected.
Interestingly, this study showed a 63% decrease in rate of
thrombosis between ports placed on the right versus the left
that trended toward significance (P = .071). This is equivalent
to a 2.7-fold increased incidence in right-sided ports inde-
pendent of venous insertion point, a finding consistent with
those observed in some studies in the current literature.8,21
However, other studies, while still coming to the conclusion
that the risk for thrombosis is higher in arm ports than chest
ports, found either a left-sided predominance or no difference
between sides regarding port thrombosis.18 The patients’ hand-
edness was not specifically analyzed in our study but we
hypothesize that this increased risk of thrombosis may be
Figure 1. Kaplan-Meier curves of time in days from port placement to
UEDVT development. All DVTs occurred within 9 months of por t
placement in both groups; see text for specic days of occurrence. DVT
indicates deep vein thrombosis; UEDVT, upper-extremity deep vein
thrombosis.

Tippit et al 7
Table 3. Relative risks of UEDVT.
BINARY RISK FACTOR NO. AT RISK NO. (%)a WITH UEDVT RELATIVE RISKb (95% CI) FISHER EXACT P VALUE
Port location
Arm 147 14 ( 9. 5) 4.76 .0056
Chest 150 3 (2.0) (1.4 0 -16 .23)
Port side
Left 157 5 (3.2) 0.37 .077
Right 140 12 (8.6) (0 .13 -1.03)
Age group
55 years or older 152 10 (6.6) 1.36 .62
54 years or younger 14 5 7 (4 .8) (0.53-3.48)
BMI group
30 or more (obese) 14 0 9 (6.4) 1.26 .63
Under 30 (nonobese) 157 8 (5 .1) (0. 5 0 - 3 .18)
Race
African American 85 5 (5.9) 1.04 1.0 0
European American 212 12 (5.7 ) (0.38-2.86)
Alcohol use
Yes 84 2 (2.4) 0.34 .17
No 213 15 (7.0) (0.08-1.45)
Tobacco use
Yes 54 4 (7.4 ) 1.39 .52
No 243 13 (5.3) (0.47- 4.08)
Histopathology
Invasive ductal carcinoma 270 16 (5.9) 1.6 0 1.0 0
All other histopathologies 27 1 (3.7) (0.22-11.60)
Metastatic disease
Yes, AJCC stage IV 52 4 ( 7.7) 1.45 .51
No, AJCC stages I-III 245 13 (5 .3) (0.49-4.27)
Very early disease
Yes, AJCC stage I 48 1 (2.1) 0.32 .33
No, AJCC stages II-IV 249 16 (6 .4) (0.04-2.39)
Estrogen receptor status
Negative 96 5 (5 .2) 0.87 1. 00
Positive 201 12 (6.0) (0.32-2.41)
Progesterone receptor status
Negative 129 9 (7.0) 1.47 .47
Positive 168 8 (4.8) (0.58-3.69)
HER2/Neu status
(Continued)

8 Breast Cancer: Basic and Clinical Research
BINARY RISK FACTOR NO. AT RISK NO. (%)a WITH UEDVT RELATIVE RISKb (95% CI) FISHER EXACT P VALUE
Negative 210 11 (5 . 2) 0.76 .59
Positive 87 6 (6.9) (0. 29-1.9 9)
Triple-negative disease
Yes 68 4 (5.9) 1.0 4 1.0 0
No 229 13 (5.7) (0.35-3.07)
Setting
Adjuvant chemotherapy 89 2 (2.2) 0.31 .11
Neoadjuva nt + palliative + non e 208 15 ( 7. 2) (0 .0 7-1. 33)
Radiotherapy
No 184 11 (6.0) 1.13 1.0 0
Yes 113 6 (5.3) (0.43-2.96)
Operator
Interventional radiology 41 2 (4. 9) 0.83 1.0 0
Surgery 256 15 (5.9) (0 .20 - 3 .51)
Abbreviations: AJCC, American Joint Committee on Cancer; BMI, body mass index; CI, condence interval; UEDVT, upper-extremity deep vein thrombosis.
aPercent of number at risk.
bRatio of the percent with UEDVT.
Table 4. Estimated incidence of catheter-related thrombosis in the current literature.
AUTHOR PORTS
ANALYZED
PORT LOCATION RESULTS
% OF PATIENTS
AFFECTED
INCIDENCE OF
THROMBOSIS (PER
1000 CATHETER-DAYS)
Klösges et al4293 Upper extremity 3.76 0.12
Mori et al14 433 Upper extremity — 0.04
Piran et al8400 Upper extremity 8.50 —
Busch et al15 512 Upper extremity 1.5 6 0.06
Lyon et al3195 Upper extremity — 0.03
Teichgräber et al16 3160 Chest —0.11
Beckers et al12 43 Chest 9.30 0.68
Goltz et al17 52 Chest 1.92 0.02
152 Upper extremity 9.86 0.09
Kuriakose et al18 273 Chest 4.76 —
149 Upper extremity 11. 41 —
Our data 15 0 Chest 2.00 —
147 Upper extremity 9.52 —
related to the increased use of the dominant hand in everyday
activities, which may result in increased shear stress within the
vessel wall, therefore creating a favorable environment for clot
formation.
It was also noted that of the 17 patients found to have
UEDVT, the average BMI was 31.5 and 76% of these 17
patients were either overweight or obese. The average BMI of
patients who did not develop UEDVT was 30.1. According to
Table 3. (Continued)

Tippit et al 9
the Centers for Disease Control and Prevention (CDC), 70.6%
of adults in Arkansas are classified as overweight or obese22 so
this finding may simply be due to the normal distribution of
our patient population. However, obesity remains a known risk
factor for venous thromboembolism (VTE) and should be
considered in choosing the location of port placement in each
individual patient.
Catheter-related thrombosis remains a well-documented
but poorly understood phenomenon. Furthermore, although
the symptoms of UEDVT are often less pronounced than
those of lower extremity DVT, outcomes in patients with can-
cer with UEDVT or LEDVT are consistently worse than that
of the general population.23 In patients with port-associated
UEDVT, it is estimated that up to 70% may be asymptomatic.11
Although the relevance of asymptomatic DVT is not well-
understood, studies suggest that the risk of evolution into
symptomatic disease is not trivial24 and the presence of a cen-
tral venous catheter creates a favorable environment for throm-
bus formation. The rate of asymptomatic UEDVT is estimated
to be between 12% and 66% in patients with cancer, and in
30% to 70% of these patients, this will become clinically sig-
nificant disease.11 One lead researcher who had initially found
no difference between the risk of thrombosis in chest and arm
ports subsequently stated that taking into account the possible
progression of asymptomatic UEDVT, the likely incidence of
clinically relevant thrombosis in patients with arm ports may
be as high as 10.5%,17 a statistically significant increase. This
finding was corroborated by a subsequent retrospective review.20
Furthermore, it has been hypothesized that even an asympto-
matic thrombus may serve as a nidus of infection for bacteria
introduced at the catheter site, increasing the risk of bacteremia
in an immunocompromised population.11
We recognize that our study does have some limitations.
With this retrospective review, we were limited to records
within our own electronic medical record. As the only
University Hospital in the state of Arkansas, we see many
patients from all areas of the state, as well as neighboring states.
Many patients seek care for acute issues at local institutions
and follow-up with us after the acute issue has resolved, so
some patients who developed UEDVT may have sought care
at a local hospital. Therefore, incidence may be underestimated
if UEDVT was reported to an outside facility and patients
failed to mention this at their clinic appointment and have
confirmatory records uploaded into our system. We also realize
that it is impossible to identify all of a patient’s underlying risk
factors for hypercoagulability. Furthermore, many patients
were likely not asked specifically about certain risk factors used
in our data collection (eg, family history of clotting disorder,
personal history of VTE), and therefore, the existing risk fac-
tors for some of these patients may be underestimated. Also,
with the exception of port revision, mechanical factors were not
taken into account in this analysis, effectively ignoring the con-
tribution of this known risk factor for thrombosis. We were
also limited to articles that were written in English and some
studies that would have undoubtedly contributed to our data
discussion were not included for this reason. In addition, there
were some studies that were not sufficiently powered and these
were not included here, although they may have been beneficial
to the overall picture. Although not a limitation of our study
itself, it is worth noting that much of the research and review
articles devoted to this subject are from the 1990s and may not
be relevant in their entirety today.
In conclusion, arm ports seem to be associated with a higher
incidence of catheter-associated UEDVT than chest ports in
patients with breast cancer receiving chemotherapy. These results
have the potential to offer guidance in effectively lowering the
inherent risk associated with central venous ports while provid-
ing necessary treatment for patients with cancer. Further investi-
gation needs to be done regarding the relationship between
laterality of port placement and risk for thrombosis, as well as the
association of increased BMI and catheter-related thrombosis.
Some research has suggested that the cephalic vein presents the
highest risk for catheter-associated UEDVT, followed by the
basilic and brachial veins, so this could be another consideration
in determining the safest location for port placement.25 Because
all DVTs in our study occurred within 9 months of placement,
and because most modern adjuvant/neoadjuvant chemotherapy
regimens take 3 to 6 months to complete, we would suggest the
removal of the port after the completion of chemotherapy to
reduce the risk of DVT. It has been suggested that low-dose
warfarin is effective for UEDVT prevention26,27 and that coagu-
lation studies are not affected, and therefore, bleeding risk is neg-
ligible. A recent meta-analysis concluded that while the risk of
catheter-associated UEDVT was significantly less with LMWH
or warfarin use, other benefits and harms were not well defined
enough to recommend prophylactic anticoagulation routinely.28
Ideally, we would be able to identify patients at increased risk for
UEDVT and determine whether they may be better served by a
traditional chest port versus the arm port, especially in the right
side of the body, or whether there is a role for prophylactic anti-
coagulation on an individual basis to provide safer care for
patients with breast cancer.
Author Contributions
Research idea & design: IM, DT. Data collection: DT, AA, IM.
Manuscript writing: DT, IM, AP, DO. Statistical analysis: ES,
IM. Patient enrollment: DO, EH, AM, MR, RHT.
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