72 
Diagnosis and Management of Pleural
Metastases and Malignant Effusion in
Breast Cancer
NICHOLAS D. TINGQUIST AND MATTHEW A. STELIGA
P Pathogenesis
leural metastases and malignant pleural effusion may occur
with metastatic breast cancer. Presentation can vary widely
from an incidental finding on imaging to a large effu-
sion with severe dyspnea. Any pleural effusion in a breast cancer
patient can be suspected to be a malignant effusion until proven
otherwise. The focus of the clinician should be to provide the
most efficient, accurate diagnosis with the least risk of complica-
tion and pain for the patient. Overall, malignant pleural effusions
account for approximately 20% to 25% of all effusions. Infec-
tious or postinfectious etiologies are the most common cause of
exudative effusion and pleural malignancies, both primary and
metastatic, are the second leading cause of exudative pleural effu-
sions,1 estimated to number approximately 150,000 annually in
the United States.1,2 Breast cancer is second only to lung cancer
as the leading cause of all pleural metastases and thus accounts
for approximately one-fourth of all malignant effusions.3,4 In
women, it is the most common cause of a malignant effusion,
accounting for up to 40%.5 In this chapter, we review the mag-
nitude and presentations of pleural metastases and malignant
pleural effusion (MPE) in breast cancer, their biochemical profiles,
and methods of diagnosis and management. A similar related
clinical entity, malignant pericardial effusion (MPCE), is also
covered.
The estimated incidence of malignant pleural involvement
in breast cancer ranges from 2% to 12%.4,6–8 Although cancer
cell–positive effusions have been noted as the initial presen-
tation of a malignancy, this is not commonly reported as the
initial diagnosis of breast cancer.9,10 Conversely, malignant breast
cancer pleural metastases are a common initial presentation of
disease progression or recurrence, occurring in 42% to 43% of
patients.8,11 Overall, in advanced breast cancer, pleural metasta-
ses are a common occurrence and are found in 36% to 65% of
advanced disseminated diseases.12–15 The time of initial breast
cancer diagnosis to the development of malignant pleural involve-
ment varies but averages 35 to 42 months.10,11 The contribution
of malignant pleural involvement by breast cancer toward the
overall mortality and morbidity of the disease depends on the
number of metastatic disease sites, total tumor burden within
the pleural space, and underlying pulmonary reserve of the
patient.
934
Although MPE can be a significant problem for those affected,
the details of its pathogenesis are not clear. It appears to be a
combination of factors leading to an overall increase in pleural
fluid production that overwhelms its removal, thereby causing
an accumulation manifest as MPE. Interestingly, pleural effu-
sion does not occur in every patient with pleural metastases.
Current research has shed light on the fact there may be certain
genetic characteristics or “secretomes” carried by these tumors
that do cause effusions. Tumor cells may produce vascular endo-
thelial growth factor (VEGF) along with a host of concomi-
tant factors. These factors interact with inflammatory cells in
the mesothelium and endothelium leading to capillary leak
into the pleural space that overwhelms the lymphatic system’s
ability to reabsorb. There is also some thought that direct tumor
invasion of the lymphatics may disrupt this drainage system
as well.16
Clinical Presentation
Symptoms associated with breast cancer pleural metastases may
be related to local and systemic effects. Unlike primary pleural
tumors, metastatic cancers to the pleural space, including breast
cancer, rarely present as bulky metastases without pleural effu-
sion.17 Dyspnea is, in general, the most common presenting
symptom and is often related to the size of the pleural effusion.
However, up to one-fourth of patients may be asymptomatic at
presentation.4
Pleural metastases from breast cancer result in dyspnea by
causing a restrictive pulmonary physiology and gas-exchange
abnormalities. The incompressible pleural fluid collection and the
limited outward chest wall excursion result in compression and
atelectasis of the underlying lung parenchyma. The reduction in
vital capacity reduces the effective gas exchange. Although the
pulmonary circulation has an adaptive hypoxic vasoconstrictive
response, this is incompletely effective when there is a large effu-
sion and when an atelectatic lobe or lung leads to significant
shunting and ventilation/perfusion mismatching. Other causes
of subjective dyspnea without significant hypoxemia include
 CHAPTER 72  Diagnosis and Management of Pleural Metastases and Malignant Effusion in Breast Cancer 935

• BOX 72.1 Causes of Dyspnea in Breast Cancer TABLE

72.1 Causes of Paramalignant Pleural Effusion
Patients
Atelectasis of lung parenchyma resulting from malignant pleural effusion Cause Transudates Exudates
Inflammatory pleurisy and chest wall pain leading to splinting
Lung parenchymal metastases Congestive heart failure from all ++++ Rarely
Pneumonia obscured by effusion causes, especially bilateral
Pulmonary thromboembolism effusions
Pneumonitis secondary to radiation Parapneumonic effusions — ++++
Left ventricular dysfunction leading to pulmonary edema
Cardiotoxicity due to antineoplastic agents Pulmonary thromboembolism +++ +
Malignant pericardial effusion and tamponade
Anemia secondary to advanced cancer or antineoplastic therapies
Postobstructive atelectasis ++++ —
Hypoalbuminemia resulting from ++++ —
cachexia

mediastinal shifting and reflex stimulation of the chest wall and Associated with ascites, +++ +
malignant or cirrhosis
lungs as a result of altered compliance (Box 72.1).18
Aside from the aforementioned causes of dyspnea, other con- Chylothorax resulting from — ++++
comitant factors may contribute to breathlessness. Anemia reduces thoracic duct obstruction
the oxygen-carrying capacity and systemic oxygen delivery and Mediastinal adenopathy, including + +++
may induce a hyperdynamic cardiac response and strain. Patients compression of pulmonary
are generally older and may have underlying degrees of congestive arteries
heart failure, which is often manifested as dyspnea. Risks of pul-
monary thromboembolism are increased secondary to hyperco- Superior vena cava syndrome ++++ —
agulable states of cancers, effects of hormonal therapy, and the Status post chest wall or — ++++
decreased mobility of many cancer patients. Pulmonary embolism mediastinal radiation
(PE) is listed as the fourth most common cause of pleural effusions Drug-induced pleural reactions — ++++
by some authors1 and must be considered in the differential diag- (bleomycin, cyclophosphamide,
nosis of a “paramalignant effusion” (Table 72.1). One-fourth of methotrexate, mitomycin,
PE-associated effusions may be transudative, but three fourths of procarbazine)
them are exudative and may confound the diagnosis of a breast
cancer–associated malignant effusion.
Malignant pericardial involvement should be suspected in a
patient with persistent dyspnea after drainage of MPE. The patient
with an MPCE may or may not have hemodynamic instability. should prompt a search for concomitant processes such as
The true incidence of MPCE associated with all breast cancer empyema, pneumonia, sepsis, pulmonary thromboembolism, or
patients is unclear, but it has been reported as high as 19% in an endobronchial metastases.
autopsy series.19 Of the subgroup of patients with known meta-
static pleural breast cancer with pericardial spread of disease, 63%
to 100% also have lung and pleural metastases at the time of Diagnosis
MPCE diagnosis.20,21 These patients with both breast MPE and Radiographic Findings
MPCE appear to have a higher frequency of bilateral malignant
effusions.21 Dyspnea may also be a result of antineoplastic thera- Plain chest radiography is the most common radiographic means
pies. Pulmonary parenchyma can be quite radiosensitive, and of identifying malignant pleural involvement. There is opacifica-
radiotherapy directed against breast cancer may scatter and lead tion of various extent of the hemithorax, ranging from blunting
to subacute radiation pneumonitis and delayed fibrosis with of the costophrenic angle on the frontal view and posterior gutter
restriction. Some cytotoxic chemotherapy agents have associated on the lateral view to complete opacification of the hemithorax,
pulmonary toxicities, or cardiotoxicity. In addition to intrinsic with or without a midline shift of the mediastinal structures.22
lung dysfunction, cytotoxic and radiation-induced immunosup- Decubitus films to confirm a free-flowing liquid layer may be
pression with concomitant structural lung damage may predispose used to follow up suspicious blunting without the classic meniscus
patients to pulmonary infections. In a clinicopathologic review of fluid sign. With the ready availability of computed tomography
the pattern of metastatic diseases and cause of death in breast (CT) scans that provide superior discrimination of tissue versus
cancer patients, the pulmonary system is the number one or two fluid, advanced three-dimensional imaging can help direct diag-
site of metastases, and infections account for about one-fourth of nosis and treatment. Contrast enhancement of the parietal pleural
the deaths.13,19 is useful in separating exudative from transudative effusions.23
Other nonspecific chest symptoms attributable to pleural More specific features of malignant pleural involvement include
metastases often include cough and, much less commonly, pleu- pleural nodularity and irregularity and pleural thickness greater
risy and chest wall pain. Tachypnea, tachycardia, and cyanosis than 1 cm.24 Pleural surfaces thus assessed with CT scanning
may be related to impaired gas exchange and hypoxemia. A large have a sensitivity of 87% and specificity of 100% for malig-
pleural effusion may transmit increased pressure to the pericar- nant involvement, although the sensitivity is lower for metastatic
dium and rarely cause a tamponade-like effect; in general, however, cancers versus primary pleural cancers.24 A large pleural effusion
hypotension is not expected. Likewise, fever and hemoptysis normally shifts the mediastinum away toward the contralateral
936 S E C T I O N XV  Management of Advanced Local, Regional, and Systemic Disease

A B C
• Fig. 72.1 Computed tomography (CT), 18-fluorodeoxy glucose positron emission tomography (FDG-
 

PET) and fused PET-CT images of pleuropulmonary metastases from breast cancer. Disseminated stage
IV breast cancer with bilateral pulmonary, mediastinal (right paratracheal and left para-aortic) nodal, right
anterior pleural, right chest wall disease. Note the absence of FDG uptake in the bilateral small dependent
pleural effusions but clear activity in the right anterior nodular pleural lesions. (A) Soft tissue window (top);
fused soft tissue window (bottom). (B) FDG-PET. (C) Soft tissue window of the lung (top); fused lung and
soft tissue windows (bottom).  (Courtesy R. Wahl and C. Cohade.)

chest, sometimes causing critical compression of vascular and
conducting airway structures. Therefore a midline undeviated
mediastinum or even ipsilaterally deviated mediastinum in the
presence of a large effusion suggests central airway obstruction
leading to complete atelectasis of the lung. This should prompt
an airway examination to look for endobronchial obstruction
resulting from tumor or volume loss resulting from inspissated
mucus. Ultrasound can complement chest films and/or CT scans
to guide bedside sampling and drainage of fluid pockets, especially
when these are small or may have become loculated, or when the
patient physiology and physiognomy such as chronic obstructive
pulmonary disease and obesity will increase the risk of complica-
tions from thoracentesis.
Most metastatic pleural effusions from breast cancer are uni-
lateral and arise in the hemithorax ipsilateral to the initial site of
disease 50% to 83% of the time.11,25,26 Although bilateral pleural
effusions have usually been attributed to left ventricular dysfunc-
tion and congestive heart failure, up to 10% of patients may have
bilateral malignant effusions.11 It should be qualified that these
studies are from the era before CT scans were routinely used to
assess disease progression or to identify pleural pulmonary involve-
ment. The routine use of CT scanning may detect many smaller
pleural effusions. Distribution of metastatic implants on the
pleural surfaces have been studied in vivo during diagnostic and
therapeutic thoracoscopy,27,28 and this has demonstrated that a
majority of the visible lesions stud the visceral pleura and the
parietal pleura.28 Given the differential blood supply and lym-
phatic drainage of the visceral and parietal pleural surfaces, this
suggests that most pleural metastases occur in combination with
and perhaps subsequent to hematogenous and lymphangitic
spread of disease to the lungs. Canto-Armengod27 observed a
preponderance of ipsilateral pleural metastases studding the costal
pleura, whereas metastases to the contralateral pleura more com-
monly affect the mediastinal pleura.
18-Fluorodeoxy glucose positron emission tomography (FDG-
PET) is accepted as an effective metabolic imaging adjunct to help
characterize abnormal-appearing tissue as likely being neoplastic,
inflammatory, or benign. FDG-PET has high sensitivity and
specificity rates in the imaging of primary pleural cancers, as in
mesothelioma.29 FDG-PET is superior to CT alone scanning in
the detection of pleural metastases in primary bronchogenic car-
cinoma, with a sensitivity approaching 90% and a specificity and
accuracy of 94.1% and 91.4%, respectively.30 In terms of breast
cancer, FDG-PET has been used for imaging and staging of
primary breast cancer, although the results for axillary and
mammary nodal staging vary and depend on nodal size and the
tumor proliferation index.31 In its evaluation of disseminated
metastatic disease in breast cancer, FDG-PET is at least as effective
as Tc99m-MDP bone scanning,32 but with regard to the pleural
space, although there are case reports,33 its efficacy in detecting
metastatic disease has not been formally evaluated.
An example of FDG-PET positive pleural, lung parenchymal,
and extrathoracic soft tissue metastases in a breast cancer patient
is presented in Fig. 72.1. The use of PET-CT scanners with fused
PET-CT imaging facilitates the localization of pleural metastases
and help distinguish these from metastases to the lung periphery,
chest wall osseus, and soft tissue structures.
Tissue Confirmation
Thoracentesis and Studies on the Pleural Fluid
The radiologic advances outlined earlier have greatly improved our
ability to detect earlier and characterize the extent of possible
pleural metastases from breast cancer. However, the broad
 CHAPTER 72  Diagnosis and Management of Pleural Metastases and Malignant Effusion in Breast Cancer 937
• Fig. 72.2  Thoracoscopic view of a pleural cavity with malignant pleural
effusion and nonspecific pleuritis of the parietal pleura.
differential of possible paramalignant effusions generally makes it
necessary to obtain a tissue diagnosis to confirm regional spread
of disease before proceeding with appropriate regional and/or
systemic therapy.
Because the presentation of malignant pleural metastases from
breast cancer is most often a pleural effusion (Fig. 72.2), symp-
tomatic or otherwise, the initial diagnostic step is removal and
analysis of fluid for diagnosis and as needed for the relief of symp-
toms. Thoracentesis can be performed “blind,” without real-time
radiologic guidance, after review of a chest film or CT scan;
however, beside ultrasonography by physicians can be a valuable
tool, especially in patients with smaller or loculated effusions. The
diagnostic yield of pleural fluid cytology varies and ranges from
40% to 90%,2 depending on the tumor type, tumor burden, and
number of thoracentesis performed. Breast cancer appears to have
a higher pleural cytologic yield than metastatic lung cancer.34
There is debate as to whether a large volume of fluid improves
diagnostic yield; practice currently varies from sending only 10 to
20 mL to more than 1 L.35 Furthermore, local laboratory practice
differs as to whether only a small aliquot is processed as a smear
or a cytospin slide or whether a larger volume is processed into a
cell block. There is evidence that the preparation of a cell block
increases the diagnostic yield from 11%35 to 38%.36 An additional
advantage of a cell block is having additional material available
for immunostaining. Routine tests performed on the pleural fluid
include chemistries to distinguish an exudate from a transudate.
Glucose, pH, lactate dehydrogenase (LDH), and cultures may be
ordered to rule out an infected or complicated postobstructive
parapneumonic effusion, one of the several causes of a paramalig-
nant effusion (see Table 72.1).1,2,17 A malignant effusion with
low glucose, low pH, and a high LDH generally portends
a worse prognosis,38 but it should not discourage the clinician
from attempting to drain and sclerose the affected space for
palliation.
Immunohistochemistry
Given the rich source of tumor markers associated with adeno-
carcinomas, and markers with greater specificity for breast cancer
in particular, there have been ongoing attempts to improve on
the diagnostic sensitivity and prognostic value of identifying a
malignant breast effusion with such molecular markers. The 2007
American Society of Clinical Oncology (ASCO) recommendations
for the use of tumor markers include the measurement of steroid
hormone receptors (estrogen and progesterone receptor status)
and HER2/neu status of the primary tumor.38 Although meta-
static effusions from breast cancer also have a high frequency of
positive estrogen receptor (ER) and progesterone receptor (PR)
staining (72% and 52%, respectively), so do ovarian metastatic
effusions, thus limiting the specificity of ER and PR staining.39
Biomarkers of tissue proliferation have also been looked for in
suspicious pleural fluid, both as an aid to diagnosis and, perhaps
in the future, as a target for specific therapy. Ki67 is a human
nuclear antigen present in cycling but not resting cells, and posi-
tive immunohistochemical labeling of suspicious but cytologically
negative effusions may obviate more invasive surgical procedures.40
VEGF has been found and measured in various malignant serous
effusions, including pleural effusions, and reaches levels 10 times
higher than that in matched sera. The use of anti-VEGF neutral-
izing antibodies in in vitro systems point the way toward possible
future targeted therapy.41
Tissue Biopsies
Pleural needle biopsy with a variety of needles had been per-
formed “blind” after confirming entry into a pocket of pleural
fluid with a finder 21-gauge or smaller needle or directly with
ultrasound. The yield of pleural needle biopsy is generally lower
than that provided by fluid cytology.2,34 Unlike diffuse granulo-
matous inflammation, sampling the patchy pleural metastases,
and especially the finding of predominantly visceral pleural
implantation (Fig. 72.3), including the inaccessible mediastinal
pleural surfaces,27,28 may explain the low additional yield. Given
the potential risk of parenchymal lung puncture, occasional life-
threatening bleeding, and the availability of more accurate mini-
mally invasive image-guided procedures, blind pleural needle
biopsies are generally of historical interest and unwarranted.
Surgical approaches for tissue diagnosis may be required when
repeated thoracentesis with or without image-guided pleural
biopsy fails to provide a tissue confirmation or when the initial
presentation suggests a multiloculated complex malignant effu-
sion. Thoracoscopic approaches, either with simple single-entry
thoracoscopy with the patient under local anesthesia and con-
scious sedation or video-assisted thoracic surgery (VATS) with the
patient under general anesthesia, have 86% to 100% diagnostic
accuracy in diagnosing a malignant pleural effusion.27,28,42,43 Con-
firmation of malignant pleural involvement based on histologic
examination of fresh-frozen tissue or the appearance under visual
examination may expedite long-term management of the involved
pleural space by pleurodesis at the end of the case, either by
mechanical or chemical means.
Treatment: Indications, Approaches,
and Complications
Intervention and management of patients with malignant pleural
effusion from metastatic breast cancer should be guided by a few
general principles. Because the presence of malignant cells in the
pleural space implies metastatic and hence incurable disease, the
goal of therapy is primarily to palliate symptoms and to anticipate
and thus avoid complications caused by pleural involvement (Box
72.2). As a rule, the development of malignant pleural involve-
ment, especially if it is one of multiple sites of metastases, por-
tends more aggressive disease, a higher tumor burden, and hence
938 S E C T I O N XV  Management of Advanced Local, Regional, and Systemic Disease

• Fig. 72.3   Macroscopic view of tumor implants on the visceral pleura.

• BOX 72.2 Management of Malignant Pleural worse outcome.44 However, given the varied responses patients
may have to cytotoxic, hormonal, and biologic agents, treatment
Effusions From Breast Cancer
must be tailored for the individual patient, taking into account
Therapeutic Thoracentesis the patient’s overall functional status, comorbidities, prior expo-
Rapid relief, easily done with local anesthetic sure to treatment, and finally the nature and extent of the pleural
Incomplete drainage, frequent recurrence involvement.
Systemic cytotoxic chemotherapy, hormonal therapy, and bio-
Percutaneous Drain Placement logic and immune therapy are covered elsewhere in detail. Suffice
Rapid relief, often complete drainage, easily done with local anesthetic, image it to say, there are select cases of MPEs that have responded to
guidance can improve efficacy
systemic therapy alone, although the specific rates of response are
Frequent recurrence once drain is removed
unknown. Therefore, for asymptomatic or minimally symptom-
Tube Thoracostomy (Chest Tube) atic metastatic breast cancer effusions in patients who are sched-
Rapid relief, often complete drainage, able to administer sclerosant (talc slurry) uled for follow-up systemic therapy, it may be reasonable to defer
through tube immediate local pleural interventions.
Significant pain The exception here is terminally ill patients with large MPEs
who are not active enough to elicit symptoms. If large effusions
Indwelling Pleural Catheter that compress the lung are not controlled, the lung can develop
Can be placed at bedside or in operating room; allows patient to drain fluid as fibrinous peel and/or tumor deposits that encase it and prevent
needed outside of hospital reexpansion, even when the fluid is drained. The patient suffers
External catheter requires care
from the so-called trapped lung and a decline in pulmonary func-
Pleuroperitoneal Shunting tion secondary to mechanical compression of the lung.45 In addi-
Generally abandoned in favor of indwelling pleural catheter tion, the residual space is prone to infection from contamination
Can be associated with abdominal complications and tube malfunction during frequent procedures, and clearance of infection in that
space can be incredibly challenging. Similarly, malignant pleural
Thoracoscopy (Video-Assisted Thoracic Surgery) effusions that develop multiple loculations are often difficult to
Ability to biopsy when diagnosis is questioned, ability to break up loculations treat. Therefore symptomatic MPEs that do not respond to sys-
and allow more thorough drainage temic chemotherapy require drainage of the pleural fluid and
Insufflation of talc is possible; at the same time, pericardial effusions can be obliteration of the pleural space.
addressed simultaneously
Requires conscious sedation or general anesthesia
Pleural Space Drainage
Open Surgical Approaches
Thoracentesis
Generally abandoned in favor of thoracoscopy; greater pain and longer hospital
stay Thoracentesis is often the first step in both the diagnosis and
treatment of MPEs from breast disease. It is not definitive,
however, because the mean recurrence interval is within 4.2 days,
 CHAPTER 72  Diagnosis and Management of Pleural Metastases and Malignant Effusion in Breast Cancer 939
and the overall recurrence rate is 98% within 30 days.3 In the case
of MPE, thoracentesis is more useful as a diagnostic technique
because there is no mechanism to prevent recurrence of fluid
accumulation or continued drainage. Despite its short therapeutic
duration, a thoracentesis not only confirms the cause of the effu-
sion but also can usually ascertain whether the fluid can be
removed and whether the lung is able to reexpand. Drainage of
up to as much as 1 to 2 L at the initial thoracentesis is warranted.
Although the sudden evacuation of more than 1.5 L of pleural
fluid of a chronically collapsed lung has been associated with
unilateral reexpansion pulmonary edema,46 this complication is
rare.47,48 Large volume thoracentesis may be better tolerated if
allowed to drain slowly or drain to gravity rather than rapid evacu-
ation with suction. In practice, we terminate the procedure at the
onset of excessive coughing and pleuritic chest pain. Any residual
fluid is aspirated at a later date. Repeated thoracentesis is reserved
for those with acute life-threatening problems, patients who are
waiting on the effects of systemic chemotherapy, and those who
are poor operative risks (Karnofsky score <30%).49 Repeated tho-
racentesis has the potential risks of inducing hypoproteinemia,
empyema, pneumothorax, and can produce intrathoracic locula-
tions of pleural fluid. Although chemical pleurodesis can theoreti-
cally be administered after thoracentesis with a needle or a
small-caliber drainage catheter, it is generally more effective when
done with VATS drainage with sclerosant insufflation or tube
thoracostomy.
Indwelling Pleural Catheter
With the advent of readily accessible bedside imaging modalities
such as ultrasound, placement of indwelling pleural catheters
(IPC) to an effusion is now a safe and efficient method for con-
tinued symptomatic relief of MPE. This method has been shown
to be superior to repeated thoracentesis in a variety of ways. It
is generally safer than repeated thoracentesis and has a higher
success rate, specifically with smaller or loculated pleural fluid
collections.50,51 In a recent case series of 80 patients with MPE,
ultrasound-guided catheter placement was met with success in
87% of the patients.51 This method is often found to be better
tolerated from a patient care standpoint. It does not require a
large skin incision or blunt dissection to accommodate a large-
bore chest drain as used in the tube thoracostomy method dis-
cussed next and has been shown to have fewer insertion-related
complications.51,52 Also in this case series of 124 patients with
various etiologies of pleural effusions, larger bore size chest tube
was not found to have an improved benefit on treatment of the
symptomatic effusion.51 One common pleural drainage system is
the PleurX drain (Denver Biomaterials, Golden, CO), a tunneled
pleural catheter with a fabric cuff that promotes ingrowth and is
suitable for permanent placement. It is easily inserted either in
the operating room or with local anesthetic at the bedside. These
systems offer continued drainage of the refractory pleural effusion
as well as being smaller, more comfortable, and more portable
than the traditional chest tube. The catheter can be easily used at
home by home health nurses, family members, or by the patient
themself. It is easily connected to disposable plastic evacuated
bottles to drain the effusion whenever it becomes symptomatic.
Repeated drainage can improve dyspnea and promote symphysis
of the visceral pleura to the parietal pleura thus obliterating the
space for recurrent effusions to develop. If no longer desired,
the catheters can be removed at the bedside with local anes-
thetic if removal is desired, but permanent placement is also
common.
Tube Thoracostomy
Classically, tube thoracostomy was employed as the first-line treat-
ment of MPE that did not resolve after thoracentesis drainage and
systemic therapy. This painful method is not well tolerated by the
conscious patient at the bedside and has not been shown to be
superior to image-guided drain placement of small-bore cathe-
ters.51,52 With increasing availability of ultrasound or CT guided
drainage, indications for large bore chest tube placement are
decreasing. One possible indication may be a patient presenting
to an emergency department in distress, without availability of
percutaneous drainage. In this case a 20- to 24-French chest tube
is inserted at the bedside, usually with the patient under intrave-
nous sedation and local analgesic infiltration. The chest tube is
placed to water seal drainage reservoir, serial chest radiographs
obtained, and chest drainage recorded. Pleurodesis can then be
performed through the tube if the lung has reexpanded and the
pleural drainage has been sufficiently low (<200 mL per 24 hours,
as is typical of our practice). Pleurodesis can be successful only if
the lung is completely reexpanded so that the parietal and visceral
pleura can oppose, otherwise pleurodesis will further “trap” the
lung in a partly collapsed state, and sclerosing agent such as
talc could become infected, which would present a clinical
challenge.
Pleurodesis
Pleurodesis can be accomplished by a variety of methods with the
introduction of the IPC and VATS but has classically been accom-
plished via tube thoracostomy. A 2016 Cochrane review of the
different management options for MPE with regard to pleurodesis
compared 16 agents with a variety of methods for instillation and
administration showed that the most effective single agent was
talc. The best improvement in subjective dyspnea scores at 30 days
posttreatment was with talc slurry administered through an IPC.53
This was associated with better patient tolerance of the procedure
and equivalent postprocedural fever.
Once the drainage is sufficiently reduced to allow chemical
pleurodesis, the patient is premedicated with a narcotic analgesic
and up to 4 mg/kg of lidocaine 1% is instilled in the tube first.
Then 50 mL saline is mixed with 5 g sterile talc sclerosant into a
slurry. The talc slurry is then instilled into the chest tube, and the
tube held in an elevated position (typically taped over the bed rail)
on water seal for 4 hours to allow the slurry to stay in the chest.
Rotation in the patient’s body position is generally unnecessary to
achieve distribution of the sclerosant within the pleural cavity.
After 4 hours, the tube is brought to a dependent position and
suction reapplied. The chest drainage is monitored on suction for
at least 48 hours. When drainage falls to less than 100 mL per 24
hours, the chest tube is removed. The process can be repeated if
needed. Median hospitalization for patients with tube thoracos-
tomy and successful pleurodesis is approximately 6 days.54–56 If
the chest drainage does not fall below 150 mL per 24 hours after
4 days, the sclerosant agent is readministered and the procedure
repeated. Further failure to respond to therapy qualifies as a failure
of conservative therapy.
It is well accepted to use small-bore (10- to 16-French) percuta-
neous catheters instead of standard large-bore (24- to 32-French)
chest tubes in the drainage and sclerotherapy of malignant pleural
effusions. Standard chest tubes limit patient mobility and are
often a source of significant discomfort. Chest tubes not only have
higher pain with placement but can also be a source of ongoing
pain while the tube is in place. Furthermore, some patients can
have chronic intercostal neuralgia. In prospective and retrospective
940 S E C T I O N XV  Management of Advanced Local, Regional, and Systemic Disease
studies, smaller catheters are better tolerated, have minimal com-
plications, and exhibit few major differences in outcomes such as
probabilities of recurrence.57–60
“Spontaneous pleurodesis” without sclerosant has been
observed with the use of a chronic, small-bore indwelling pleural
catheter (Pleurx, Denver Biomaterials).61,62
Surgical Intervention: Video-Assisted
Thoracoscopic Surgery, Pleural Decortication,
Pericardial Drainage
If diagnosis is in question, or pleurodesis has failed and a
malignant pleural effusion recurs, thoracoscopy (VATS) is a
useful diagnostic and therapeutic tool. VATS offers a magni-
fied view of the hemithorax, thus the extent of pleural metas-
tases, including the degree of tumor encasement of the lung,
can be determined. Options for therapeutic maneuvers include
lysis of adhesions, limited decortication, pleurectomy, mechani-
cal and chemical pleurodesis, and visual positioning of drainage
tubes.55 Complete decortication is difficult and not likely of sig-
nificant benefit, but limited decortication with VATS can allow
lung expansion in some with loculated effusions. Insufflation
with talc (i.e., talc poudrage) then follows. Mechanical pleurode-
sis with an abrasive pad can be done to achieve pleurodesis,
but as tumor deposits may be vascularized, this could result in
unnecessary oozing or bleeding and should be considered with
caution. Bilateral effusions can be treated with sequential VATS
plus pleurodesis. The operative mortality of VATS for pleurode-
sis in patients with advanced malignant pleural effusions is
approximately 5%.63,64
A less common, but often more urgent, clinical scenario
referred for surgical evaluation is pericardial effusion in either a
patient with known or suspected metastatic breast cancer. This
may vary from incidental finding of pericardial effusion on
imaging to a patient with hemodynamic instability and impend-
ing cardiac tamponade. It is of paramount importance to under-
stand the patient’s overall clinical condition and goals of care to
provide the best treatment for MPCE. Options for treatment
include the following: ultrasound-guided pericardiocentesis,
ultrasound-guided pericardial drain placement, surgical pericar-
dial drainage, and pericardial window. Pericardiocentesis can be
rapidly achieved at the bedside, as can ultrasound-guided drain
placement. Unfortunately, recurrence is common and results in
the same clinical scenario. A more durable palliation may be
achieved with open drainage of the pericardial sac if the patient
is able to undergo surgery. Subxiphoid drainage may be the fastest
surgical route in a hemodynamically unstable patient. In the more
stable patient, other options exist. One common approach is to
perform thoracoscopy to drain pleural effusion, and during the
thoracoscopy, the pericardium is widely opened so the pericardial
effusion may drain into the pleural space, and an IPC can then
be placed in the pleural space, which may help relieve both MPE
and MPCE with one drain.
Surgical Pleurectomy
With modern-day therapies available for MPEs, pleurectomy is
largely anachronistic. This procedure, with its high operative mor-
bidity and mortality, cannot be justified as a palliative measure
and has been replaced by interventions with lower morbidity
rates.
Patients With Trapped Lung
If the effusion has not been controlled or is loculated, the lung
could be trapped (>25% pleural dead space). Similarly, the lung
can become trapped as a result of encasement by extensive tumor
involvement, and the tumor implants cannot be removed during
surgery. A trapped lung that cannot expand leaves pleural dead
space that will rapidly reaccumulate fluid and nullify any attempts
at pleurodesis. A pleuroperitoneal shunt, usually the Denver shunt
(Codman and Shurtleff, Randolph, MA), has been placed as an
alternative.65,66 These shunts are placed in the pleural space and
the peritoneum and have a pumping chamber that sits in a sub-
cutaneous pocket at the anterolateral costal margin. Patients must
actively pump this chamber, often up to 25 times every 4 hours;
thus, patient compliance is an important issue. Another obvious
issue with this is the distribution of malignant cells and/or infec-
tion from the pleural space into the peritoneal space. The incon-
venience and complications of this type of drain, including
abdominal complications, have led most to abandon it in favor
of a tunneled IPC, which is drained externally. In general, patients
with a trapped lung present difficult management problems, and
proper selection of the most appropriate palliative option must be
done on an individual basis.
Sclerosing Agents
Many agents have been used to affect pleural symphysis.2,17,37,67,68
Most have a direct irritant effect, usually eliciting an intense
pleural inflammation and subsequent fibrosis. A number of anti-
neoplastic agents have also been administered locally into the
pleural space, with the purported dual cytotoxic and fibrotic
action on the involved pleural surfaces.14,69,70 Most of these reports
consist of small case series without a comparator arm. The results
appear encouraging from some studies, such as with mitoxantrone
in two small case series of 18 and 6 patients, with a 72% to 100%
response (complete response and partial response), with a pro-
longed median survival of 17 months as measured against histori-
cal survival of less than 12 months from the time of pleural
metastases.67,70 Other compounds, such as radioactive phospho-
rus, thiotepa, and 5-fluorouracil, either offered no additional
benefit over drainage alone or required concomitant sclerosants
to be effective.71
Because of its efficacy, ready availability, and relative lesser
expense, talc remains the agent of choice for chemical pleurode-
sis.55,56,64,72–79 The route of administration, either talc slurry or
thoracoscopic talc insufflation, was evaluated in a randomized trial
of 482 patients with MPE due to a variety of primary tumors.
Methods were similar in efficacy overall; however, the subgroup
with MPE due to lung or breast primary had higher success with
thoracoscopy compared with talc slurry through a tube (82% vs.
67%).80 There remain safety concerns regarding the episodic
development of posttalc instillation respiratory complications,
ranging from transient hypoxemia to acute respiratory distress
syndrome (ARDS), with some patient deaths.81–83 The patho-
physiology of this posttalc syndrome remains unclear, and the
frequency and severity of response may be related to the dosage
and talc particle size used in pleurodesis.37,84 Current recommen-
dation is to limit the amount of talc used to 5 g per instillation.
Research has demonstrated a reduction in talc-related ARDS with
administration of “graded” or “large particle” talc showing reduced
systemic uptake which has been the suggested method of its
pathogenesis.53,85 Sclerosis of the pericardial space with talc is not
 CHAPTER 72  Diagnosis and Management of Pleural Metastases and Malignant Effusion in Breast Cancer 941
advised for concerns of pericarditis, but thiotepa has been reported
as an effective sclerosing agent for MPCE.86
Prognosis
The development of malignant effusion in a breast cancer patient
generally portends a poor prognosis, with a median survival time
of 5 to 15.7 months.11,25,26,44,74 Patients with metastatic pleural
disease as the solo manifestation of relapse have a significant sur-
vival advantage over those with more widespread disease: 48
months versus 12 months in one series.44 The concomitant pres-
ence of invasion into other mesothelium-lined cavities, including
the pericardium and peritoneum, are especially ominous signs.
Summary
Malignant involvement of the pleural space by breast cancer is a
common occurrence late in the course of progressive disease and
may be a major cause of morbidity. Because of the broad differ-
ential causes of pleural effusions, including contralateral or bilat-
eral effusions, a tissue diagnosis should be obtained rather than
assuming a malignant cause. If a malignant cause has been ascer-
tained, it is certainly a sign of incurable disease and further man-
agement should be focused on symptom control and patient
comfort.
Diagnosis should first be attempted through the use of thora-
centesis. Samples should be sent for fluid cytology as well as
chemistry studies to determine whether they are exudative. A cell
block should be requested and will improve the diagnostic yield
of fluid cytology. A second attempt at pleural fluid cytology may
be attempted, or the patient may be referred for diagnostic tho-
racoscopy. Closed pleural needle biopsy is seldom warranted,
although it may be performed by experienced practitioners during
the second thoracentesis, especially if diagnostic thoracoscopy is
not readily available. Thoracoscopy has a very high diagnostic
yield and can allow simultaneous therapeutic drainage of effusion
and effective pleurodesis by mechanical means or by talc insuffla-
tion. Open surgical biopsy or drainage thoracotomy is seldom
necessary. More recently, indwelling pleural catheters have shown
great promise for MPE management and have been shown to be
highly effective with talc administration as a sclerosant agent for
pleurodesis.
Selected References
1. Light RW. Pleural Diseases. 3rd ed. Baltimore: Williams & Wilkins;
1995.
2. Anthony VB, et al. Management of malignant pleural effusions:
official statement of the American Thoracic Society. Am J Respir Crit
Care Med. 2000;162:1987.
16. Stathopoulos GT, Kalomenidis I. Malignant pleural effusion:
tumor-host interactions unleashed. Am J Respir Crit Care Med.
2012;186:487-492.
50. Daniels CE, Ryu JH. Improving the safety of thoracentesis. Curr
Opin Pulm Med. 2011;17:232-236.
51. Abusedera M, Alkady O. Ultrasound-guided pleural effusion drain-
age with a small catheter using the single-step trocar or modified Seld-
inger technique. J Bronchol Intervent Pulmonol. 2016;23:138-145.
53. Clive AO, Jones HE, Bhatnagar R, Preston NJ, Maskell N. Interven-
tions for the management of malignant pleural effusions: a network
meta-analysis. Cochrane Database Syst Rev. 2016;(5):CD010529.
62. Putnam JB Jr, et al. Outpatient management of malignant pleural
effusion by a chronic indwelling pleural catheter. Ann Thorac Surg.
2000;69:369.
80. Dresler CM, Olak J, Herndon JE II, et al. Phase III intergroup study
of talc poudrage vs talc slurry sclerosis for malignant pleural effusion.
Chest. 2005;127:909-915.
86. Cozzi S, Montanara S, Luraschi A, et al. Management of neoplastic
pericardial effusions. Tumori. 2010;96:926.
A full reference list is available online at ExpertConsult.com.
 CHAPTER 72  Diagnosis and Management of Pleural Metastases and Malignant Effusion in Breast Cancer 941.e1
References
1. Light RW. Pleural Diseases. 3rd ed. Baltimore: Williams & Wilkins;
1995.
2. Anthony VB, et al. Management of malignant pleural effusions:
official statement of the American Thoracic Society. Am J Respir Crit
Care Med. 2000;162:1987.
3. Anderson CB, Philpott GW, Ferguson TB. The treatment of malig-
nant pleural effusions. Cancer. 1974;33:916.
4. Chernow B, Sahn S. Carcinomatous involvement of the pleura: an
analysis of 96 patients. Am J Med. 1977;63:695.
5. Johnston WW. The malignant pleural effusion: a review of cytopa-
thologic diagnosis of 584 specimens from 472 consecutive patients.
Cancer. 1985;56:905.
6. Apfelstaedt JP, Muller AG. Breast cancer complicated by pleural
effusions. J Surg Oncol. 1995;58:173.
7. Kreisman H, et al. Breast cancer and thoracic metastasis: review of
119 patients. Thorax. 1983;38:175.
8. Weichselbaum R, Marck A, Hellman S. Pathogenesis of pleural
effusion in carcinoma of the breast. Int J Radiat Oncol Biol Phys.
1977;2:963.
9. Monte SA, Ehya H, Lang WR. Positive effusion cytology as the
initial presentation of malignancy. Acta Cytol. 1987;31:448.
10. Van de Molengraft FJ, Vooijs GP. The interval between the diagnosis
of malignancy and the development of effusions, with reference to
the role of cytologic diagnosis. Acta Cytol. 1988;32:183.
11. Fentiman IS, et al. A pleural effusion in breast cancer: a review of
105 cases. Cancer. 1981;61:295.
12. Abrams HC, Spiro R, Goldstein N. Metastases in carcinoma: analy-
sis of 1000 autopsied cases. Cancer. 1950;3:74.
13. Cho SY, Choi HY. Causes of death and metastatic patterns in
patients with mammary cancer: ten-year autopsy study. Am J Clin
Pathol. 1980;73:232.
14. Fracchia AA, et al. Intrapleural chemotherapy for effusion from
metastatic breast carcinoma. Cancer. 1970;26:626.
15. Goldsmith HS, et al. Pulmonary lymphangitic metastases from
breast carcinoma. Arch Surg. 1967;94:483.
16. Stathopoulos GT, Kalomenidis I. Malignant pleural effusion:
tumor-host interactions unleashed. Am J Respir Crit Care Med.
2012;186:487-492.
17. Sahn SA. Malignant pleural effusion. In: Fishman AP, ed. Pul-
monary Diseases and Disorders. 2nd ed. New York: McGraw-Hill;
1988.
18. Estenne M, Yernault JC, DeTroyer A. Mechanism of relief of
dyspnea after thoracentesis in patients with large pleural effusions.
Am J Med. 1983;74:813.
19. Hagemeister FB, et al. Causes of death in breast cancer. Cancer.
1980;46:162.
20. McKenna RJ, et al. Pleural and pericardial effusions in cancer
patients. Curr Probl Cancer. 1985;9:2.
21. Swanepoel E, Apffelstaedt JP. Malignant pericardial effusion in
breast cancer: terminal event or treatable complication? J Surg Oncol.
1997;64:308.
22. Bonomo L, et al. Malignant pleural disease. Eur J Radiol. 2000;
34:98.
23. Aquino SL, Webb WR, Gushiken BJ. Pleural exudates and
transudates: diagnosis with contrast-enhanced CT. Radiology.
1994;192:803.
24. Traill Z, Davies R, Gleeson F. Thoracic computed tomography in
patients with suspected malignant pleural effusions. Clin Radiol.
2001;56:193.
25. Banerjee AK, et al. Pleural effusion in breast cancer: a review of the
Nottingham experience. Eur J Surg Oncol. 1994;20:33.
26. Raju RN, Kardinal CG. Pleural effusion in breast carcinoma: analy-
sis of 122 cases. Cancer. 1981;48:2524.
27. Canto-Armengod A. Macroscopic characteristics of pleural metasta-
ses arising from the breast and observed by diagnostic thoracoscopy.
Am Rev Respir Dis. 1990;142:616.
28. Fentiman IS, Rubens RD, Hayward JL. The pattern of metastatic
disease in patients with pleural effusions secondary to breast cancer.
Br J Surg. 1982;69:193.
29. Marom EM, et al. The role of imaging in malignant pleural meso-
thelioma. Semin Oncol. 2002;29:26.
30. Gupta N, et al. Clinical role of F-18 fluorodeoxyglucose positron
emission tomography imaging in patients with lung cancer and
suspected malignant pleural effusion. Chest. 2002;122:1918.
31. Wahl RL. Current status of PET in breast cancer imaging, staging,
and therapy. Semin Roentgenol. 2001;3:250.
32. Cook GJ, Fogelman I. Skeletal metastases from breast cancer:
imaging with nuclear medicine. Semin Nucl Med. 1999;29:69.
33. Suarez M, et al. Early diagnosis of recurrent breast cancer with
FDG-PET in patients with progressive elevation of serum tumor
markers. Q J Nucl Med. 2002;46:113.
34. Prakash UB, Reiman HM. Comparison of needle biopsy with cyto-
logic analysis for the evaluation of pleural effusion: analysis of 414
cases. Mayo Clin Proc. 1985;60:158.
35. Sallach SM, et al. Volume of pleural fluid required for diagnosis of
pleural malignancy. Chest. 2002;122:1913.
36. Dekker A, Bupp PA. Cytology of serous effusions: an investigation
into the usefulness of cell blocks versus smears. Am J Clin Pathol.
1978;70:855.
37. Rodriguez-Panadero F, Anthony VB. Pleurodesis: state of the art.
Eur Respir J. 1997;10:1648.
38. Harris L, et al. American Society of Clinical Oncology 2007 update
of recommendations for the use of tumor markers in breast cancer.
J Clin Oncol. 2007;25:33.
39. Lee BH, et al. WT1, estrogen receptor, and progesterone receptor
as markers for breast or ovarian primary sites in metastatic adeno-
carcinoma to body fluids. Am J Clin Pathol. 2002;117:745.
40. Saleh H, Bober P, Tabaczka P. Value of Ki67 immunostain in
identification of malignancy in serous effusions. Diagn Cytopathol.
1998;20:24.
41. Verheul HM, et al. Targeting vascular endothelial growth factor
blockade: ascites and pleural effusion formation. Oncologist. 2000;
5(suppl 1):45.
42. Boutin C, et al. Thoracoscopy in malignant pleural effusions. Am
Rev Respir Dis. 1981;124:588.
43. Hori T, et al. Therapeutic and life-prolonging effect of intra-
pleural injection with a streptococcal preparation, OK-432, and
IL2-cultured effusion lymphocytes to breast cancer patients with
malignant pleural effusion. Biotherapy. 1992;5:21.
44. Poe RH, et al. Survival of patient with pleural involvement by breast
carcinoma. Am J Clin Oncol. 1983;6:523.
45. Leff A, Hopewell PC, Costello J. Pleural effusion from malignancy.
Ann Intern Med. 1978;88:532.
46. Ratliff JL, et al. Reexpansion pulmonary edema. Chest. 1973;64:654.
47. Mahfood S, et al. Reexpansion pulmonary edema. Ann Thorac Surg.
1988;45:340.
48. Tarver RD, Broderick LS, Conces DJ Jr. Reexpansion pulmonary
edema. J Thorac Imaging. 1996;11:198.
49. Karnofsky DA, Burchenal JH. Clinical evaluation of chemothera-
peutic agents in cancer. In: MacLeod CM, ed. Evaluation of Chemo-
therapeutic Agents. New York: Columbia University Press; 1949.
50. Daniels CE, Ryu JH. Improving the safety of thoracentesis. Curr
Opin Pulm Med. 2011;17:232-236.
51. Abusedera M, Alkady O. Ultrasound-guided pleural effusion drain-
age with a small catheter using the single-step trocar or modified Seld-
inger technique. J Bronchol Intervent Pulmonol. 2016;23:138-145.
52. Havelock T, Teoh R, Laws D, et al. Pleural procedures and thoracic
ultrasound: British Thoracic Society Pleural Disease Guideline 2010.
Thorax. 2010;65:61-76.
53. Clive AO, Jones HE, Bhatnagar R, Preston NJ, Maskell N. Interven-
tions for the management of malignant pleural effusions: a network
meta-analysis. Cochrane Database Syst Rev. 2016;(5):CD010529.
54. Heffner JE, et al. Clinical efficacy of doxycycline for pleurodesis.
Chest. 1994;105:1743.
941.e2 S E C T I O N XV  Management of Advanced Local, Regional, and Systemic Disease
55. Yim AP, et al. Thoracoscopic talc insufflation versus talc slurry
for symptomatic malignant pleural effusion. Ann Thorac Surg.
1996;62:1655.
56. Zimmer PW, et al. Prospective randomized trial of talc slurry vs
bleomycin in pleurodesis for symptomatic malignant pleural effu-
sions. Chest. 1997;112:430.
57. Clementsen P, et al. Treatment of malignant pleural effusion:
pleurodesis using a small percutaneous catheter—a prospective ran-
domized study. Respir Med. 1998;92:593.
58. Morrison MC, et al. Sclerotherapy of malignant pleural effusion
through sonographically placed small-bore catheters. AJR Am J
Roentgenol. 1992;158:41.
59. Parker LA, Charnock GC, Delany DJ. Small bore catheter drain-
age and sclerotherapy for malignant pleural effusions. Cancer.
1989;64:1218.
60. Pollak JS, et al. Treatment of malignant pleural effusions with
tunneled long-term drainage catheters. J Vasc Intervent Radiol.
2001;12:201.
61. Putnam JB Jr, et al. A randomized comparison of indwelling pleural
catheter and doxycycline pleurodesis in the management of malig-
nant pleural effusions. Cancer. 1999;86:1992.
62. Putnam JB Jr, et al. Outpatient management of malignant pleural
effusion by a chronic indwelling pleural catheter. Ann Thorac Surg.
2000;69:369.
63. Ohri SK, et al. Early and late outcome after diagnostic thoracoscopy
and talc pleurodesis. Ann Thorac Surg. 1992;53:1038.
64. Schulze M, et al. Effective treatment of malignant pleural effusion
by minimal invasive thoracic surgery: thoracoscopic talc pleurode-
sis and pleuroperitoneal shunts in 101 patients. Ann Thorac Surg.
2001;71:1809.
65. Lee KA, et al. Management of malignant pleural effusions with
pleuroperitoneal shunting. J Am Coll Surg. 1994;178:586.
66. Tsang V, Fernando HC, Goldstraw P. Pleuroperitoneal shunt for
recurrent malignant pleural effusions. Thorax. 1990;45:369.
67. Feuilhade F, et al. Efficacy and toxicity of intrapleural mitoxan-
trone: apropos of 18 cases of pleural metastases of breast cancer. Bull
Cancer. 1989;76:361.
68. Figlin R, et al. Intrapleural chemotherapy without pleurodesis for
malignant pleural effusions. LCSG Trial 861. Chest. 1994;106:363S.
69. Colleoni M, et al. Intracavitary chemotherapy with thiotepa in
malignant pericardial effusions: an active and well-tolerated regimen.
J Clin Oncol. 1998;16:2371.
70. Kikuchi K, et al. Intrapleural administration of CDDP against
malignant pleural effusions in breast cancer. Gan to Kagaku Ryoho.
1990;17:1905.
71. Contegiacomo A, et al. The treatment of metastatic pleural effusion
in breast cancer: report of 25 cases. Tumori. 1987;73:611.
72. de Campos JR, et al. Thoracoscopy talc poudrage: a 15-year experi-
ence. Chest. 2001;119:801.
73. Diacon AH, et al. Prospective randomized comparison of thoraco-
scopic talc poudrage under local anesthesia versus bleomycin instil-
lation for pleurodesis in malignant pleural effusions. Am J Respir Crit
Care Med. 2000;162:1445.
74. Fentiman IS, Rubens RD, Hayward JL. Control of pleural effu-
sions in patients with breast cancer: a randomized trial. Cancer.
1983;52:737.
75. Fentiman IS, Rubens RD, Hayward JL. A comparison of intracavi-
tary talc and tetracycline for the control of pleural effusions second-
ary to breast cancer. Eur J Cancer Clin Oncol. 1986;22:1079.
76. Hamed H, et al. Comparison of intracavitary bleomycin and talc for
control of pleural effusions secondary to carcinoma of the breast. Br
J Surg. 1989;76:1266.
77. Milanez RC, et al. Intrapleural talc for the treatment of malignant
pleural effusions secondary to breast cancer. Cancer. 1995;75:2688.
78. Sanchez-Armengol A, Rodriguez-Panadero F. Survival and talc
pleurodesis in metastatic pleural carcinoma, revisited: report of 125
cases. Chest. 1993;104:1482.
79. Viallat JR, et al. Thoracoscopic talc poudrage pleurodesis for malig-
nant effusions: a review of 360 cases. Chest. 1996;110:1387.
80. Dresler CM, Olak J, Herndon JE II, et al. Phase III intergroup study
of talc poudrage vs talc slurry sclerosis for malignant pleural effusion.
Chest. 2005;127:909-915.
81. Brant A, Eaton T. Serious complications with talc slurry pleurodesis.
Respirology. 2001;6:181.
82. Light RW. Talc for pleurodesis? Chest. 2002;122:1506.
83. Rehse DH, Aye RW, Florence MG. Respiratory failure following talc
pleurodesis. Am J Surg. 1999;177:437.
84. Ferrer J, et al. Talc preparations used for pleurodesis vary markedly
from one preparation to another. Chest. 2001;119:1901.
85. Maskell NA, Lee YCG, Gleeson FV, et al. Randomized trials describ-
ing lung inflammation after pleurodesis with talc of varying particle
size. Am J Respir Crit Care Med. 2004;170:377-382.
86. Cozzi S, Montanara S, Luraschi A, et al. Management of neoplastic
pericardial effusions. Tumori. 2010;96:926.