Defining the role of PET-CT in staging early breast cancer.
ABSTRACT Currently, there is a lack of data on the role of combined positron emission tomography-computed tomography (PET-CT) in the staging of early invasive primary breast cancer. We therefore evaluated the role of (18)F-fluorodeoxyglucose ((18)F-FDG)-PET-CT in this patient population.
We prospectively recruited 70 consecutive patients (69 women, one man; mean age, 61.9 ± 8.1 years) with early primary breast cancer for staging with (18)F-FDG-PET-CT. All PET-CT images were interpreted by two readers (independently of each other). A third reader adjudicated any discrepancies. All readers had ≥5 years of specific experience. Ethics board approval and informed consent were obtained.
The mean clinical follow-up was 22.7 ± 12.6 months. The primary tumor was identified with PET-CT in 64 of 70 patients. Of the unidentified lesions, surgical pathology revealed two intraductal carcinomas, one invasive tubular carcinoma, and three invasive lobular carcinomas. Undiagnosed multifocal breast disease was shown in seven of 70 patients. PET-CT identified avid axillary lymph nodes in 19 of 70 patients, compared with 24 of 70 confirmed during surgery. There were four patients who were axillary node positive on PET but had no axillary disease at surgery. Five patients were reported with avid metastases. Two of those patients were treated for metastatic disease (nodal, lung, and liver in one and bone metastases in the other) following further imaging and clinical assessment. In the other three patients, lesions (lung, n = 1; pleural, n = 1; paratrachael node, n = 1) were subsequently diagnosed as benign lesions.
Integrated (18)F-FDG-PET-CT may have a role in staging patients presenting with early breast cancer.
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ABSTRACT: It is widely believed by both doctors and patients that regular follow-up with imaging is important for patients who have been treated for early breast cancer. In reality, current evidence does not support this. Randomised trials have shown no benefit for intensive versus routine follow-up and studies have also shown that follow-up by a general practitioner or nurse specialist is likely to be as effective as by a breast cancer specialist. Specifically there is no evidence that specialised imaging including PET/CT is of any benefit. Newer approaches including the assessment of circulating tumour cells and/or circulating tumour DNA may eventually prove advantageous, but currently must be considered experimental. In summary, current evidence suggests that there is no basis for intensive follow-up beyond standard regular clinical assessment and annual mammography following treatment of early breast cancer. There may be better models for follow-up than the traditional resource-intensive hospital outpatient visit, including nurse-led open access follow-up. Monitoring for long-term sequelae of treatment is becoming as important as the detection of recurrence in an era where long-term survival is increasingly common.Breast (Edinburgh, Scotland) 08/2013; 22S2:S156-S160. · 2.09 Impact Factor
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ABSTRACT: Although positron emission tomography (PET) imaging may not be used in the diagnosis of breast cancer, the use of PET/computed tomography is imperative in all aspects of breast cancer staging, treatment, and follow-up. PET will continue to be relevant in personalized medicine because accurate tumor status will be even more critical during and after the transition from a generic metabolic agent to receptor imaging. Positron emission mammography is an imaging proposition that may have benefits in lower doses, but its use is limited without new radiopharmaceuticals.Radiologic Clinics of North America 09/2013; 51(5):781-98. · 1.95 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the clinical impact of the preoperative (18)F-FDG PET/CT in the initial workup of breast cancer with clinically negative axillary nodes. Whether the status of the clinical axillary nodal involvement can be considered a parameter for making a decision to omit the preoperative (18)F-FDG PET/CT in the situation reported herein was also determined. A total of 178 patients who had newly diagnosed breast cancer and for whom the conventional diagnostic modalities showed no sign of axillary node metastasis were retrospectively enrolled in this study. All the patients underwent preoperative (18)F-FDG PET/CT. The images and histologic results that were obtained were analyzed. (18)F-FDG PET/CT detected primary lesions in 156 of the 178 patients, with an overall sensitivity of 87.6 %, and false negative results were obtained for 22 patients (12.4 %). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of (18)F-FDG PET/CT in the detection of axillary nodes were 20.8, 86.9, 37.0, 74.8, and 69.1 %, respectively. Extra-axillary node metastasis was identified in two patients (1.1 %) who had internal mammary nodes. There was no distant metastasis, but coexisting primary tumor was detected in five patients (2.8 %). In total, the therapeutic plan was changed based on (18)F-FDG PET/CT in seven (3.9 %) of the 178 patients, but considering only the cases confined to breast cancer, the change occurred in only two patients (1.1 %). (18)F-FDG PET/CT almost did not affect the initial staging and treatment plan in breast cancer with clinically negative axillary node. If the axillary node is clinically negative in the preoperative workup of breast cancer, then (18)F-FDG PET/CT can be omitted.Breast Cancer Research and Treatment 03/2014; · 4.47 Impact Factor
Defining the Role of PET–CT in Staging Early Breast Cancer
ASHLEY M. GROVES,aMANU SHASTRY,aSIMONA BEN-HAIM,aIRFAN KAYANI,aANMOL MALHOTRA,b
TIMOTHY DAVIDSON,bTINA KELLEHER,bDIANE WHITTAKER,bMARIE MEAGHER,aBRIAN HOLLOWAY,b
RUTH M. WARREN,cPETER J. ELL,aMOHAMMED R. KESHTGARb
aInstitute of Nuclear Medicine, University College London, London, United Kingdom;bBreast Unit Royal
Free Hospital, UCL, London, United Kingdom;cDepartment of Radiology, Addenbrooke’s Hospital,
University of Cambridge, Cambridge, United Kingdom
Key Words. Breast cancer • Computed tomography • Spiral • Positron emission tomography • Staging
Disclosures: Simona Ben-Haim: Spectrum-Dynamics (C/A). The other authors indicated no financial relationships.
(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (H) Honoraria received; (OI) Ownership interests; (IP)
Intellectual property rights/inventor/patent holder; (SAB) Scientific advisory board
combined positron emission tomography–computed to-
mography (PET–CT) in the staging of early invasive pri-
mary breast cancer. We therefore evaluated the role of
Methods. We prospectively recruited 70 consecutive pa-
tients (69 women, one man; mean age, 61.9 ? 8.1 years)
with early primary breast cancer for staging with18F-
FDG-PET–CT. All PET–CT images were interpreted by
two readers (independently of each other). A third reader
specific experience. Ethics board approval and informed
consent were obtained.
Results. The mean clinical follow-up was 22.7 ? 12.6
months. The primary tumor was identified with PET–CT in
64 of 70 patients. Of the unidentified lesions, surgical pathol-
ogy revealed two intraductal carcinomas, one invasive tubu-
lar carcinoma, and three invasive lobular carcinomas.
70 patients. PET–CT identified avid axillary lymph nodes in
19 of 70 patients, compared with 24 of 70 confirmed during
surgery. There were four patients who were axillary node
positive on PET but had no axillary disease at surgery.
those patients were treated for metastatic disease (nodal,
lowing further imaging and clinical assessment. In the
other three patients, lesions (lung, n ? 1; pleural, n ? 1;
paratrachael node, n ? 1) were subsequently diagnosed as
Conclusion. Integrated18F-FDG-PET–CT may have a
Breast cancer is a common disease with a highly variable out-
come , and therefore accurate tumor staging is important.
18F-fluorodeoxyglucose positron emission tomography (18F-
malignancies . This reflects PET’s inherent sensitivity over
other imaging modalities . However, the role of PET in the
staging of primary breast cancer is less clear and there is only
limited evidence, as recently highlighted . Initial studies
showed the potential for PET in this respect, but most studies
PET–CT over stand-alone PET has shown added value for
many malignancies [10, 11], and such findings have also been
suggested for breast cancer . These findings are intuitive;
the CT component aids localization of PET findings, whereas
it may identify soft tissue and bone changes beyond the spatial
resolution of radionuclide imaging . The role of18F-FDG-
Telephone: 44-207-380-9206; Fax: 44-207-436-0603; e-mail: firstname.lastname@example.org
publication February 28, 2012; first published online in The Oncologist Express on April 26, 2012. ©AlphaMed Press 1083-7159/2012/
Received August 10, 2011; accepted for
recognized [14–16], and the use of PET–CT to phenotype
breast cancer by imaging metabolic flow relationships has
been shown [17, 18].
Current recommendations do not incorporate the routine
use of18F-FDG-PET–CT for staging primary breast cancer
. However, the direct scientific evidence to support this rec-
ommendation is limited. There have been prospective investi-
gations with18F-FDG-PET–CT in patients with advanced
primary breast cancer [19, 20] and in high-risk or recurrent pa-
tients [21–23]. Other studies combined whole-body18F-FDG-
PET–CT with PET–CT mammography  or compared
diffusion-weighting magnetic resonance imaging (MRI) and
PET–CT , but the data were obtained in patients with
known metastatic disease.
The lack of evidence for the role of PET–CT in primary
tive data suggesting that PET–CT may indeed have a role in
breast cancer staging have recently become available, which
further highlighted the need for prospective investigations
. Here, we present the findings from a prospective study
investigating the role of18F-FDG-PET–CT in the staging of
patients with early primary breast carcinoma.
MATERIALS AND METHODS
We prospectively recruited 70 consecutive eligible consenting
patients (69 women and one man; mean age, 61.9 ? 8.1 years)
with early primary unilateral invasive breast cancer for18F-
FDG-PET–CT staging. Eligibility included patients with pri-
mary tumors sized 1.0–3.5 cm (mean size, 2.1 ? 0.7 cm) as
measured on imaging. Patients aged ?45 years, pregnant pa-
tients, and patients with inflammatory breast carcinoma were
excluded. The only other exclusion was patients declining to
take part. All patients had undergone triple assessment includ-
ing mammography, ultrasound, and core biopsy prior to re-
cruitment. These tests were performed before the PET–CT
study. The mean time from PET–CT to surgery was 2.4 ? 2.1
weeks. Although some patients at our institutions receive MRI
clinically, breast MRI was not part of this study. In this patient
cohort, bone scintigraphy, liver ultrasound, and CT were not
performed because these patients had early disease.
Axillary node staging was performed using sentinel lymph
node scintigraphy (performed after the PET–CT exam) in 59
patients. In nine patients, ultrasound-guided nodal biopsy con-
firmed metastasis (prior to the PET–CT examination). The re-
maining two patients had large multicentric lesions with
enlarged axillary nodes on ultrasound. However, subsequent
axillary clearance showed no metastasis. A clinical and histo-
logical profile of the study patients is presented in Table 1 and
in supplemental online Table 1.
Ethics board approval and informed consent was obtained.
Following 6 hours of fasting prior to examination (ensuring a
blood glucose level ?10 mmol/L in all patients), images were
acquired 1 hour after injecting 200 MBq of18F-FDG using a
dedicated combined PET–64-detector-CT (VCT-XT Discov-
ery; GE-Healthcare Technology, Waukesha, WI). A CT scan
was performed (for attenuation correction) using 64-mm ?
kVp and 80 mA in 0.8 seconds) from vertex to mid-thigh. Oral
but not i.v. CT contrast medium was administered. Maintain-
ing the patient position, an18F-FDG-PET scan was performed
that covered an area identical to that covered by the CT scan.
All PET acquisitions were carried out in two-dimensional
mode (8 minutes per bed position, compensating for the re-
duced administered activity, minimizing radiation exposure).
Transaxial emission images of 3.27 mm thickness (pixel size,
3.9 mm) were reconstructed using ordered subsets expectation
maximization with two iterations and 28 subsets. The axial
sition. The images were reconstructed as a 128 ? 128 matrix.
Table 1. Profile of the patient population
3064 (? 6
24 (versus 19
N1 24 (versus 19
Type of tumor
Abbreviations: ER, estrogen receptor; HER-2, human
epidermal growth factor receptor 2; PET–CT, positron
emission tomography–computed tomography; PR,
PET–CT in Staging Early Breast Cancer
PET–CT Image Interpretation
(GE Healthcare Technology, Waukesha, WI). On the dual-
screen work station, the PET and CT datasets were both dis-
played as separate but coregistered images and also displayed
using color (PET) images fused with CT. All readers had ac-
cess to all these datasets. All the PET–CT images were inter-
preted by two readers (independently of each other). A third
of specific experience. The only clinical data provided to the
readers was primary breast carcinoma. The readers were un-
and CT images were reviewed by all readers. The PET–CT re-
porting and acquisitions used current European cancer guide-
line criteria and standardizations .
Histology was performed as per routine clinical management
using the surgically excised specimens (mastectomy in 20 pa-
tients and wide local excision in 50 patients).
The population size was determined as 70 using a proportion of
p ? 90% and a precision of 6% (in our estimation), including an
illary node metastasis. ? statistics were used to assess interob-
server variability in the staging of early breast cancer with PET–
for axillary node metastasis calculation. All statistics were per-
formed using SPSS 2011 software (IBM; Armonk, NY).
The primary tumor was identified in 64 of 70 patients. The mean
two invasive ductal carcinomas, one invasive tubular carcinoma,
and three invasive lobular carcinomas (Table 2).
Undiagnosed multifocal disease was shown on PET–CT in
seven of 70 patients (Table 3 and Fig. 1). This was not identi-
fied by mammography or ultrasound. Multifocal disease was
confirmed by histopathology in all cases.
Axillary Lymph Node Staging
All patients were staged using histology as the gold standard.
PET–CT identified avid axillary lymph nodes in 19 of 70 pa-
tients, compared with 24 of 70 confirmed on histology. There
were four patients who were axillary node positive on PET but
had no axillary disease at surgery (Table 4). In total, 18 nodes
were obtained at surgery and histologically analyzed. The
maximum short axis diameter (in mm) in the nodes of these
four patients on CT were 6.4, ?5, 11.2, and 15.6.
ROC curve analysis revealed an SUVmaxthreshold of 1.4
Extra-Axillary FDG-Avid Foci
70 patients. One of these patients, aged 75 years with a 2.2-cm
intermediate-grade lobular estrogen receptor–positive carci-
noma, had widespread avid skeletal disease, which was also
identified on CT (Fig. 2). The most avid skeletal lesion had an
SUVmaxof 19.5. The second patient, aged 54 years with a
Table 2. Size on imaging and histology of the six tumors
not identified by PET–CT
Tumor Size (cm)
Many of these tumors were at the lower end of the
inclusion criteria and thus close to the limits of spatial
resolution for PET [33, 34].
Abbreviations: IDC, invasive ductal carcinoma; ILC,
invasive lobular carcinoma; ITC, invasive tubular
carcinoma; PET–CT, positron emission tomography–
Table 3. Location of multifocal disease in the seven
patients in whom this was diagnosed on a case-by-case
(histology) main tumor
Location of Location of second
Case 1 (NST)Left breast close
Posterior to main
Medial and superficial
to the main lesion
Adjacent to main
Superficial and medial
to the main lesion
One lesion medial and
a second lesion lateral
to the main lesion
Adjacent to the main
lesion in the upper
Adjacent lesion in
inner quadrant and
second one in outer
Case 2 (IDC)
Case 3 (IDC)Right central
Left upper outerCase 4 (IDC)
Case 5 (IDC) Left upper inner
Case 6 (IDC)Left upper outer
Case 7 (IDC)Right lower
Abbreviations: IDC, invasive ductal carcinoma; NST,
Groves, Shastry, Ben-Haim et al.
3.5-cm intermediate-grade ductal estrogen receptor–positive
carcinoma, had nodal disease above and below the diaphragm
with lymph node, liver, and lung nodule (the largest was 7 mm
and avid) involvement. The most avid distant lesion in that pa-
tient had an SUVmaxof 6.0.
In the remaining three patients, the lesions were subse-
quently believed to be benign. In one of those patients, biopsy
of a moderately avid pleural nodule revealed a fibroma. In the
second patient (treated with trastuzumab), who had a mildly
lung nodules and the patient remained disease free 25 months
after the PET–CT study. In the last patient, with a moderately
avid paratracheal lymph node on PET–CT imaging, clinical
follow-up for 31 months showed no evidence of disease recur-
rence off treatment.
The mean clinical follow-up period was 22.7 ? 12.6
months. To date there is no evidence of false-negative meta-
The ? statistic for tumor, node, and metastasis reporting were
0.91, 0.83, and 0.86, respectively.
Original, prospective18F-FDG-PET–CT data from 70 patients
with primary early breast carcinoma are presented. Over 95%
of the invasive ductal carcinomas were identified on PET–CT,
study, distant PET findings that were reported as metastatic
were found in 7% of patients and previously undetected mul-
tifocal disease was identified in 9% of patients. Patient breast
cancer management was directly affected in nine (13%) pa-
with multifocal disease. Our findings from early breast cancer
mirror the results of18F-FDG-PET–CT scanning in patients
 of cases. Given the useful biological correlates of FDG-
PET in primary breast cancer , there is a need for further
assessment of FDG-PET–CT for primary breast cancer.
metastases alter patient management and provide additional
ease also significantly alter the management pathway and
again impact prognosis, and thereby aid targeted individual-
ized treatment for the patient . In both these cases, sys-
temic therapy is indicated. In one case in this study, a pleural
abnormality detected on PET required additional ultrasound
and biopsy to determine the etiology; these showed a benign
pleural tumor, illustrating the effort needed to obtain the cor-
rect diagnosis. The findings of unidentified multifocal breast
disease in seven patients also impacted patient management;
these patients require mastectomy instead of wide local exci-
sions. MRI and mammography are useful to diagnose multifo-
cal disease, but their diagnostic accuracy is limited . MRI
has nonetheless been shown to be useful in the management of
breast cancer with the potential of reducing unnecessary sur-
gery [31, 32].
Table 4. Axillary nodal PET–CT and surgical histology
No nodal metastasis
The sensitivity was 62.5% (95% CI, 40.7%–80.5%) and
the specificity was 91.3% (95% CI, 78.3%–97.2%).
Abbreviations: CI, confidence interval; PET–CT, positron
emission tomography–computed tomography.
mography–computed tomography of a patient with newly diag-
nosed primary breast cancer. The maximum intensity projection
image shows multifocal disease in the left breast (solid arrows).
Avid left axillary nodal uptake is also identified (dashed arrow).
No distant FDG-avid disease is identified.
18F-fluorodeoxyglucose (FDG) positron emission to-
PET–CT in Staging Early Breast Cancer
. Both the size of the lesion and the intensity of tracer up-
take are important determinants for lesion detectability with
PET. Phantom studies show that lesions ?5 mm are not reli-
ably detected on PET . Thus, it is not surprising that mi-
crometastases (?2 mm) are not detected, and indeed a recent
technology assessment showed that the smallest axillary node
detected was 3 mm . One can improve the sensitivity of
axillary nodal metastasis detection by reducing the SUV
threshold, but this can negatively impact specificity. There-
fore, low-grade18F-FDG nodal uptake may simply represent
inflammatory (reactive) changes and thus give rise to false-
positive findings. Our findings confirm the presence of both
false-negative and false-positive lymph nodes, which is con-
sistent with a large multicenter study using stand-alone PET
. The sensitivity and specificity in our study were higher,
and this may reflect the contribution of the CT component of
PET–CT over PET-only scanners. Compared with a recent
health technology assessment, our data showed similar accu-
racy in diagnosing axillary disease, with high specificity but
limited sensitivity . Although PET–CT is limited for axil-
lary staging, a recent study showed that PET/CT may extend
the use of sentinel lymph node biopsy over more invasive
Generally, conventional imaging modalities such as
whole-body CT and liver ultrasound are not routinely used in
astatic disease at the time of breast cancer diagnosis is ?4%
[36, 37], then the rationale for such a strategy may be justified.
However, the detection of anatomical changes using conven-
tional cross-sectional imaging is less sensitive than the pico-
molar sensitivity of PET . Moreover, whole-body PET–CT
gives the potential of synergistic diagnostic performance by
combining the spatial resolution of multidetector CT data with
the metabolic sensitivity of PET. Our findings in patients with
early breast cancer, along with PET–CT findings in patients
with more advanced primary disease [19, 20], confirm that, in
many cases, there is potential to change patient management.
In order to evaluate the usefulness of PET–CT for early
breast cancer management, many factors need to be assessed.
First, the true incidence of18F-FDG-PET–CT–detectable dis-
ease in various stages of primary breast cancer needs to be de-
termined and systematically measured. Then, how this
detection alters patient management, survival, and quality of
avidity that are later found to be benign should not be over-
also give important prognostic information, for example,18F-
FDG uptake has been shown to predict survival and angiogen-
esis in lung cancer patients [38–40]. This type of additional
information is needed, but is limited in breast cancer. Second,
the cost to patients of undergoing PET–CT needs to be as-
sessed, such as radiation exposure and inconvenience. Finally,
the cost of performing18F-FDG-PET–CT to the health service
provider needs to be accurately calculated. These factors are
complex, and much more data are needed than presently exist
to perform a health technology assessment. There would ap-
primary breast cancer. The maximum intensity projection image (A) shows widespread avid disease including the right scapula, right 6th
rib and the T6 vertebra (see arrows). The fused PET–CT image (B) shows that focal avidity in the pelvis coregisters to the bony pelvis.
Groves, Shastry, Ben-Haim et al.
such as the recent COMICE (comparative effectiveness of
MRI in breast cancer) study that evaluated MRI staging .
Studies of the type undertaken here have inherent limita-
tions. Breast cancer is a heterogeneous disease . In this re-
spect, we were able to obtain a relatively homogeneous cohort
in terms of early disease, histology, and lack of presurgical
neoadjuvant chemotherapy or radiotherapy. A larger patient
population would have been helpful, but this would have sig-
nificantly increased the recruitment and follow-up periods. It
ence of metastatic disease than to exclude it. Therefore, a lon-
ger follow-up period would have been ideal, but this should be
balanced against the need to obtain data that are lacking in the
We present original prospective data on the use of18F-FDG-
limited literature on advanced primary breast cancer, PET–CT
early primary breast carcinoma. Given that the current recom-
mendations for primary breast cancer do not routinely advocate
the use of PET–CT for staging, our findings highlight the recent
call for a randomized, controlled trial to further investigate the
role of PET–CT in breast cancer staging .
We thank Dr. Manuel Rodriguez-Justo for histopathological
support. We thank Dr. John Dickson for his academic physics
assistance and Nick Papathanasiou for his statistical input.
The majority of the funding in this study was provided by
portion of funding from the Department of Health’s NIHR
Biomedical Research Centre’s funding scheme.
J. Ell, Mohammed R. Keshtgar
Collection and/or assembly of data: Ashley M. Groves, Manu Shastry, Tina
Kelleher, Diane Whittaker, Marie Meagher, Ruth M. Warren, Peter J. Ell,
Mohammed R. Keshtgar
Data analysis and interpretation: Ashley M. Groves, Manu Shastry,
Simona Ben-Haim, Irfan Kayani, Anmol Malhotra, Timothy Davidson,
Brian Holloway, Ruth M. Warren, Peter J. Ell, Mohammed R. Keshtgar
Manuscript writing: Ashley M. Groves, Manu Shastry, Simona Ben-Haim,
Irfan Kayani, Anmol Malhotra, Timothy Davidson, Brian Holloway, Ruth
M. Warren, Peter J. Ell, Mohammed R. Keshtgar
Final approval of manuscript: Ashley M. Groves, Manu Shastry, Simona
Ben-Haim, Irfan Kayani, Anmol Malhotra, Timothy Davidson, Tina
Kelleher, Diane Whittaker, Marie Meagher, Brian Holloway, Ruth M.
Warren, Peter J. Ell, Mohammed R. Keshtgar
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