DOI: 10.1148/rg.27si075507
RadioGraphics 2007;27:S197-S213
© RSNA, 2007
FDG PET/CT for the Detection and Evaluation of Breast Diseases: Usefulness and Limitations1
Hyo Soon Lim, MD,
Woong Yoon, MD,
Tae Woong Chung, MD,
Jae Kyu Kim, MD,
Jin Gyoon Park, MD,
Heoung Keun Kang, MD,
Hee Seung Bom, MD, and
Jung Han Yoon, MD
1 From the Departments of Diagnostic Radiology (H.S.L., W.Y., T.W.C., J.K.K., J.G.P., H.K.K.), Nuclear Medicine (H.S.B.), and Surgery (J.H.Y.), Chonnam National University Medical School, Chonnam National University Hwasun Hospital, 160 Ilsimri, Hwasuneup, Hwasungun, Jeollanam-do 519-809, South Korea. Presented as an education exhibit at the 2006 RSNA Annual Meeting. Received February 20, 2007; revision requested March 20 and received April 9; accepted April 18. All authors have no financial relationships to disclose.
Address correspondence to H.S.L. (e-mail: nico1220{at}dreamwiz.com).
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Abstract
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Positron emission tomography (PET) with fluorine 18 fluorodeoxyglucose (FDG) is used to diagnose, stage, and monitor breast cancer. FDG PET has the capability to depict abnormal metabolic activity before any anatomic change occurs; however, in the absence of identifiable anatomic structures on PET images, it may be impossible to identify the location of areas of increased radionuclide uptake. In such cases, the coregistration of PET images with images from computed tomography (CT) may help improve diagnostic accuracy and lead to better clinical management of patients with breast cancer. Although FDG PET/CT may have limited diagnostic value for detecting small primary breast tumors, well-differentiated breast cancer, or regional lymph node involvement, it is superior to conventional imaging modalities for detecting distant metastases and recurrences and for monitoring the response to therapy.
© RSNA, 2007
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LEARNING OBJECTIVES FOR TEST 6
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After reading this article and taking the test, the reader will be able to:- Define the advantages of FDG PET/CT over PET and other conventional imaging modalities in cancer staging.
- Describe the use of FDG PET/CT in patients with breast cancer.
- Identify the pitfalls of FDG PET/CT in evaluating breast disease.
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Introduction
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Positron emission tomography (PET) with fluorine 18 fluorodeoxyglucose (FDG) has become an essential imaging modality for the diagnosis, staging, and restaging of various cancers because it provides valuable metabolic information. PET can demonstrate abnormal metabolic activity in organs that do not appear abnormal morphologically. However, in the absence of identifiable anatomic structures, the accurate anatomic localization of foci of increased metabolic activity may be difficult or impossible with PET alone.
The coregistration of PET images with images from computed tomography (CT) allows combined anatomic and functional imaging with a single scanner. Combined PET/CT provides information that cannot be obtained with PET or CT alone and is rapidly assuming a critical role in the clinical evaluation of patients with cancer for staging and evaluating the effect of treatment. Equivocal CT findings can be evaluated better with the help of the additional functional information provided by FDG PET, especially in follow-up of cancer patients who have undergone surgery, radiation therapy, or chemotherapy. Conversely, subtle metabolic findings at FDG PET that might be confused with normal physiologic uptake may allow the detection of pathologic sites of FDG accumulation when combined with findings at CT.
In patients with breast cancer, FDG PET has been used for diagnosing, staging, and restaging cancers and for monitoring the response to therapy (1–4). PET/CT further improves the diagnostic accuracy and clinical management of patients with breast cancer (5,6). This article describes the normal physiologic pattern of FDG uptake in the breast, as well as pathologic patterns of FDG uptake in various breast diseases. The role of PET/CT in the diagnosis of breast cancer, evaluation of regional lymph nodes, monitoring of the treatment response, and restaging is discussed in detail. In addition, some common pitfalls and limitations of PET/CT, which may lead to false-negative or false-positive results in the evaluation of breast disease, are reviewed.
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FDG PET/CT for Tumor Imaging
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FDG Uptake
Tumor imaging with FDG PET is based on the fact that malignant tumors with high metabolic rates take up more glucose and FDG than do surrounding tissues. After FDG is administered intravenously, it is transported into the cells by glucose transporter proteins, just as unlabeled deoxyglucose would be. However, because malignant tumor cells express more-specific transporter proteins with a greater affinity for glucose than those expressed by normal cells, there is increased glucose flow into the cancerous cells (7).
Subsequently, the FDG is phosphorylated by hexokinase to form FDG-6-phosphate. The cell membrane is impermeable to both glucose-6-phosphate and FDG-6-phosphate. However, the latter cannot be further degraded via the glycolysis pathway, nor can it easily undergo dephosphorylation by glucose-6-phosphatase. Ultimately, FDG-6-phosphate remains trapped within the cell; and the more FDG there is in the cells, the greater the uptake in the tumor (8).
Tumor cells are not the only cells that exhibit increased FDG uptake. There are many reports of lesions with a high concentration of inflammatory cells, such as neutrophils and activated macrophages, which also show increased FDG uptake. Because of this effect, tissue areas that are normal and noncancerous but involved in processes of infection, inflammation, or healing may be mistaken for malignancies in patients with proved or suspected cancer (9).
FDG PET images are generally assessed qualitatively or quantitatively for pathologically increased radiotracer uptake. The standardized uptake value (SUV), a semiquantitative measurement, is widely used for this purpose. The SUV tends to be higher in tumors than in benign lesions; the higher the SUV of a mass, the more likely the mass is to be malignant.
Advantages of PET/CT over PET Alone
FDG PET is a strictly functional imaging modality; it produces images that lack anatomic landmarks for precise morphologic orientation. Therefore, it is often difficult to pinpoint the location of an area with increased FDG uptake. Unless anatomic images are available for correlation, sites of pathologic FDG accumulation easily may be confused with areas of normal physiologic uptake, and vice versa.
Integrated PET/CT was introduced in the late 1990s and is performed by using a CT scanner and a PET scanner that are assembled as a single unit. 
PET/CT has major advantages over PET alone: The coregistration of PET images with CT images helps accurately localize regions of abnormally increased uptake, a task that would be difficult or impossible on the basis of PET alone (Figs 1, 2). Conversely, equivocal CT findings may be interpreted more precisely with the help of the additional functional information provided by PET. As a result, the overall sensitivity and specificity of information provided by PET or CT alone is improved with PET/CT (10,11).
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Figure 1a. Invasive ductal carcinoma in a 52-year-old woman with a palpable breast mass. (a) US image shows an irregular hypoechoic mass (arrows) with a diameter of approximately 7 cm in the right breast. The posterior aspect of the mass could not be fully evaluated with US. A US-guided biopsy was performed, and cancer was diagnosed on the basis of pathologic analysis. PET/CT then was performed for pretreatment staging. (b) Axial CT attenuation–corrected PET image shows hypermetabolic lesions in the right breast and axilla. (c) Axial fused PET/CT image helped localize areas of FDG uptake (arrowheads) indicative of invasion of the pectoralis muscle.
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Figure 1b. Invasive ductal carcinoma in a 52-year-old woman with a palpable breast mass. (a) US image shows an irregular hypoechoic mass (arrows) with a diameter of approximately 7 cm in the right breast. The posterior aspect of the mass could not be fully evaluated with US. A US-guided biopsy was performed, and cancer was diagnosed on the basis of pathologic analysis. PET/CT then was performed for pretreatment staging. (b) Axial CT attenuation–corrected PET image shows hypermetabolic lesions in the right breast and axilla. (c) Axial fused PET/CT image helped localize areas of FDG uptake (arrowheads) indicative of invasion of the pectoralis muscle.
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Figure 1c. Invasive ductal carcinoma in a 52-year-old woman with a palpable breast mass. (a) US image shows an irregular hypoechoic mass (arrows) with a diameter of approximately 7 cm in the right breast. The posterior aspect of the mass could not be fully evaluated with US. A US-guided biopsy was performed, and cancer was diagnosed on the basis of pathologic analysis. PET/CT then was performed for pretreatment staging. (b) Axial CT attenuation–corrected PET image shows hypermetabolic lesions in the right breast and axilla. (c) Axial fused PET/CT image helped localize areas of FDG uptake (arrowheads) indicative of invasion of the pectoralis muscle.
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Figure 2a. Abscess in a 58-year-old woman with a palpable breast lesion and a previously detected lung mass. (a) Axial CT attenuation–corrected PET image shows a focus of intense FDG uptake (maximum SUV, 11.5) (arrow) in the right anterior thorax. Exact localization of the area of increased uptake (confined to the breast or extending to the chest wall) was difficult on the basis of PET images. (b) Axial CT image shows an isoattenuating lesion (arrow) in the chest wall beneath the breast. (c) Axial PET/CT image shows areas of increased FDG uptake indicative of hypermetabolic lesions in the chest wall (arrow) and lung (arrowhead). (d) US image shows an ill-defined hypoechoic lesion (arrows) in the chest wall. At pathologic analysis, the lesion was diagnosed as a tuberculous abscess. Inflammation surrounding the abscess led to the increased FDG uptake.
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Figure 2b. Abscess in a 58-year-old woman with a palpable breast lesion and a previously detected lung mass. (a) Axial CT attenuation–corrected PET image shows a focus of intense FDG uptake (maximum SUV, 11.5) (arrow) in the right anterior thorax. Exact localization of the area of increased uptake (confined to the breast or extending to the chest wall) was difficult on the basis of PET images. (b) Axial CT image shows an isoattenuating lesion (arrow) in the chest wall beneath the breast. (c) Axial PET/CT image shows areas of increased FDG uptake indicative of hypermetabolic lesions in the chest wall (arrow) and lung (arrowhead). (d) US image shows an ill-defined hypoechoic lesion (arrows) in the chest wall. At pathologic analysis, the lesion was diagnosed as a tuberculous abscess. Inflammation surrounding the abscess led to the increased FDG uptake.
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Figure 2c. Abscess in a 58-year-old woman with a palpable breast lesion and a previously detected lung mass. (a) Axial CT attenuation–corrected PET image shows a focus of intense FDG uptake (maximum SUV, 11.5) (arrow) in the right anterior thorax. Exact localization of the area of increased uptake (confined to the breast or extending to the chest wall) was difficult on the basis of PET images. (b) Axial CT image shows an isoattenuating lesion (arrow) in the chest wall beneath the breast. (c) Axial PET/CT image shows areas of increased FDG uptake indicative of hypermetabolic lesions in the chest wall (arrow) and lung (arrowhead). (d) US image shows an ill-defined hypoechoic lesion (arrows) in the chest wall. At pathologic analysis, the lesion was diagnosed as a tuberculous abscess. Inflammation surrounding the abscess led to the increased FDG uptake.
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Figure 2d. Abscess in a 58-year-old woman with a palpable breast lesion and a previously detected lung mass. (a) Axial CT attenuation–corrected PET image shows a focus of intense FDG uptake (maximum SUV, 11.5) (arrow) in the right anterior thorax. Exact localization of the area of increased uptake (confined to the breast or extending to the chest wall) was difficult on the basis of PET images. (b) Axial CT image shows an isoattenuating lesion (arrow) in the chest wall beneath the breast. (c) Axial PET/CT image shows areas of increased FDG uptake indicative of hypermetabolic lesions in the chest wall (arrow) and lung (arrowhead). (d) US image shows an ill-defined hypoechoic lesion (arrows) in the chest wall. At pathologic analysis, the lesion was diagnosed as a tuberculous abscess. Inflammation surrounding the abscess led to the increased FDG uptake.
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Another advantage of PET/CT over PET alone is the shorter image acquisition time. The total scanning time is reduced because PET/CT allows almost simultaneous acquisition of both anatomic and molecular information without moving the patient from one scanner to another. In addition, it allows the use of the CT scan data for attenuation correction, enabling a more accurate quantitative or semiquantitative assessment of the PET findings.
Normal Physiologic Uptake
After FDG is injected intravenously, it is distributed throughout the bloodstream and is taken up by glycolytically active tissues. Imaging is typically started at least 60 minutes after the injection, to allow sufficient blood pool clearance.
Normal physiologic uptake is observed in the brain, myocardium, and urinary tract. To a lesser extent, uptake is observed in the liver, spleen, bone marrow, gastrointestinal tract, testes, and skeletal muscles. Other less frequent sites of uptake include the endometrium, major and minor salivary glands, and brown fat in the supraclavicular and paraspinal regions (12).
Occasionally, uptake is observed in the breast. The lactating breast has been reported to show FDG uptake related to increased glucose trapping in active glandular tissue (13). Tissue density and hormonal status also affect the uptake of FDG in the breast (Fig 3); dense breasts have significantly greater FDG uptake than do fatty breasts (14). However, the ability to discriminate between benign and malignant breast lesions is unlikely to be affected by normal physiologic uptake in the breast, because the average SUV of normal breast tissue is low (14).
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Figure 3a. Increased FDG uptake in both breasts at whole-body PET/CT performed for cancer screening in a 43-year-old woman. (a) Axial PET/CT image shows areas of diffuse FDG uptake (maximum SUV, 2.2) in both breasts because of higher than normal tissue density. (b) Both craniocaudal mammograms show dense breast tissue, which has higher FDG uptake at PET than does fatty breast tissue.
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Figure 3b. Increased FDG uptake in both breasts at whole-body PET/CT performed for cancer screening in a 43-year-old woman. (a) Axial PET/CT image shows areas of diffuse FDG uptake (maximum SUV, 2.2) in both breasts because of higher than normal tissue density. (b) Both craniocaudal mammograms show dense breast tissue, which has higher FDG uptake at PET than does fatty breast tissue.
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FDG PET/CT in Breast Carcinoma
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Diagnosis of Primary Tumors
Early detection is the most effective strategy for reducing mortality from breast cancer. At present, mammography is the only screening method that has been shown to affect patient survival. Conventional imaging modalities such as mammography and US rely primarily on changes in anatomic structure for disease detection. FDG PET can help detect accelerated metabolic activity that occurs before anatomic structural changes; however, because of the expense of the examination and the radiation exposure involved, it is not generally suitable for routine screening purposes.
Various investigators have assessed the role of FDG PET in the detection of primary breast cancer and differentiation of malignancy from benign disease. The results of most studies of diagnostic performance with FDG PET have been encouraging, with sensitivity ranging between 80% and 96% and specificity between 83% and 100% (15–20). The specificity of FDG PET for differentiating benign from malignant lesions has approached 90% in most studies. An SUV range of 2.0–2.5 is frequently used as the cut-off for discriminating benign lesions from malignant ones (15,20).
The results of most studies show that the capability of PET to depict lesions smaller than 1 cm in diameter is constrained by limited spatial resolution. PET also is of limited use for identifying tumors that are well differentiated histologically, such as ductal carcinoma in situ, and slow-growing cancers such as tubular carcinoma (15,17, 18,20,21). PET is less sensitive for the detection of invasive lobular carcinoma than for that of invasive ductal carcinoma (Figs 4, 5). Different growth patterns of invasive lobular carcinoma, such as low tumor cell density and diffuse infiltration of the surrounding tissue, may help explain its lower FDG uptake (22).
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Figure 4a. Invasive ductal carcinoma in a 42-year-old woman. (a) US image shows a lobular hypoechoic mass (arrows) in the right breast. The mass was diagnosed as carcinoma on the basis of pathologic analysis of a specimen from US-guided biopsy. PET/CT was performed for pretreatment staging. (b) Axial PET/CT image shows markedly increased FDG uptake (maximum SUV, 8.9) indicative of hypermetabolism in the lesion (arrow).
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Figure 4b. Invasive ductal carcinoma in a 42-year-old woman. (a) US image shows a lobular hypoechoic mass (arrows) in the right breast. The mass was diagnosed as carcinoma on the basis of pathologic analysis of a specimen from US-guided biopsy. PET/CT was performed for pretreatment staging. (b) Axial PET/CT image shows markedly increased FDG uptake (maximum SUV, 8.9) indicative of hypermetabolism in the lesion (arrow).
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Figure 5a. Invasive lobular carcinoma in a 50-year-old woman. (a) US image shows an irregular hypoechoic mass (arrows) in the left breast. After a US-guided biopsy, the mass was diagnosed as carcinoma. PET/CT was performed for pretreatment staging. (b) Axial PET/CT image shows slight FDG uptake (maximum SUV, 2.0) in the mass (arrow), a finding characteristic of invasive lobular carcinoma; an invasive ductal carcinoma would have shown more marked uptake.
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Figure 5b. Invasive lobular carcinoma in a 50-year-old woman. (a) US image shows an irregular hypoechoic mass (arrows) in the left breast. After a US-guided biopsy, the mass was diagnosed as carcinoma. PET/CT was performed for pretreatment staging. (b) Axial PET/CT image shows slight FDG uptake (maximum SUV, 2.0) in the mass (arrow), a finding characteristic of invasive lobular carcinoma; an invasive ductal carcinoma would have shown more marked uptake.
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The role of PET/CT in patients with breast cancer has been assessed in only a few studies, but the specificity of FDG PET generally improves significantly with the use of PET/CT. Tatsumi et al (23) compared the performance of PET, CT, and PET/CT; diagnostic confidence was higher with PET/CT than with PET or CT alone in more than 50% of patients and more than 50% of regions with increased FDG uptake. Identification of the exact anatomic location of FDG uptake (whether within the breast or extending to the chest wall) is often difficult with PET alone but is achievable with the anatomic information provided by PET/CT.
Evaluating Regional Lymph Node Status
In patients with breast cancer, axillary nodal status is an important prognostic indicator. The best procedure for examining lymph nodes is axillary lymph node dissection, but it is associated with significant costs and potential morbidity, including lymphedema, restricted arm and shoulder movement, and numbness of the upper arm skin. Sentinel lymph node biopsy has become the accepted initial method for nodal evaluation. Nevertheless, sentinel lymph node biopsy is also an invasive procedure that prolongs surgery. The ability of a noninvasive test to predict nodal metastasis accurately could obviate sentinel node evaluation and lead directly to axillary dissection.
An important advantage of FDG PET is its ability to depict malignant disease in lymph nodes that do not appear pathologically enlarged at CT (Fig 6). However, although high sensitivity and specificity have been reported for axillary lymph node staging with FDG PET (20,24–26), the general opinion is that the modality is not sufficiently accurate to be used in place of axillary node sampling for routine staging of axillary involvement. Even microscopic metastases may be important for prognosis and treatment planning (27), but small axillary metastases are frequently missed at FDG PET because of the limited spatial resolution. The modality cannot demonstrate the number of lymph nodes involved, but that number is an important prognostic factor. In addition, FDG uptake in lymph nodes is not specific for malignancy; a generalized inflammatory response of regional lymph nodes to infection or recent biopsy or surgery is also a common source of increased FDG uptake.
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Figure 6a. Local metastasis at PET/CT performed for pretreatment staging of invasive ductal carcinoma in a 65-year-old woman. (a) Axial CT image shows an enlarged lymph node (arrow) in the left axillary area, a finding that was not considered to represent metastasis. (b) Axial PET/CT image shows high FDG uptake (maximum SUV, 4.2) in the lymph node (arrow), a finding suggestive of metastasis. Metastasis was confirmed at pathologic analysis.
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Figure 6b. Local metastasis at PET/CT performed for pretreatment staging of invasive ductal carcinoma in a 65-year-old woman. (a) Axial CT image shows an enlarged lymph node (arrow) in the left axillary area, a finding that was not considered to represent metastasis. (b) Axial PET/CT image shows high FDG uptake (maximum SUV, 4.2) in the lymph node (arrow), a finding suggestive of metastasis. Metastasis was confirmed at pathologic analysis.
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To our knowledge, no previously published study has concentrated on the value of PET/CT for the diagnosis of regional lymph node metastasis in patients with breast cancer. PET/CT may improve sensitivity and accuracy in the assessment of lymph node metastasis. A possible advantage of PET/CT for the evaluation of regional lymph nodes in particular is its greater accuracy for detecting and locating metastases in the internal mammary and supraclavicular lymph nodes (Fig 7). The main shortcoming of PET/CT is the difficulty of detecting lesions smaller than 1 cm because of the spatial resolution limits of PET.
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Figure 7a. Regional metastases at PET/CT performed for pretreatment staging of invasive ductal carcinoma in a 62-year-old woman. (a) Axial PET/CT image shows an area of high FDG uptake (maximum SUV, 12.0) (arrowhead) in the left breast. (b) Axial PET/CT image shows a left supraclavicular lymph node (arrow) with high FDG uptake (maximum SUV, 5.5). (c) Maximum intensity projection reconstruction of CT attenuation–corrected PET image data shows invasive ductal carcinoma (arrowhead) in the left breast and multiple metastases in the left axillary and supraclavicular lymph nodes (arrows).
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Figure 7b. Regional metastases at PET/CT performed for pretreatment staging of invasive ductal carcinoma in a 62-year-old woman. (a) Axial PET/CT image shows an area of high FDG uptake (maximum SUV, 12.0) (arrowhead) in the left breast. (b) Axial PET/CT image shows a left supraclavicular lymph node (arrow) with high FDG uptake (maximum SUV, 5.5). (c) Maximum intensity projection reconstruction of CT attenuation–corrected PET image data shows invasive ductal carcinoma (arrowhead) in the left breast and multiple metastases in the left axillary and supraclavicular lymph nodes (arrows).
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Figure 7c. Regional metastases at PET/CT performed for pretreatment staging of invasive ductal carcinoma in a 62-year-old woman. (a) Axial PET/CT image shows an area of high FDG uptake (maximum SUV, 12.0) (arrowhead) in the left breast. (b) Axial PET/CT image shows a left supraclavicular lymph node (arrow) with high FDG uptake (maximum SUV, 5.5). (c) Maximum intensity projection reconstruction of CT attenuation–corrected PET image data shows invasive ductal carcinoma (arrowhead) in the left breast and multiple metastases in the left axillary and supraclavicular lymph nodes (arrows).
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Initial Preoperative Staging
Current staging methods after the initial diagnosis of breast cancer include chest radiography, US, and bone scintigraphy. Positive or equivocal findings may lead to further evaluations with CT and MR imaging, biopsy, or both.
The most important advantage of FDG PET or PET/CT compared with other imaging modalities is the capability of detecting unsuspected distant metastases during a single whole-body examination. The reported overall sensitivity and specificity of PET for the detection of distant metastases were 86% and 90%, respectively (28). The additional information that PET/CT may provide about unsuspected distant metastases (Fig 8) could affect clinical management.
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Figure 8a. Extensive metastatic disease at PET/CT performed for pretreatment staging of invasive ductal carcinoma in a 48-year-old woman. (a–c) Axial fused PET/CT images of the upper thorax (a), abdomen (b), and pelvis (c) show multiple areas of increased FDG uptake. (d) Maximum intensity projection reconstruction of CT attenuation–corrected PET image data shows extensive metastases in the liver, bones (left clavicle, both scapulae, sternum, ribs, cervical spine, thoracolumbar spine, pelvis, and both femora), and lymph nodes (axillary, neck, aortocaval, and portacaval).
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Figure 8b. Extensive metastatic disease at PET/CT performed for pretreatment staging of invasive ductal carcinoma in a 48-year-old woman. (a–c) Axial fused PET/CT images of the upper thorax (a), abdomen (b), and pelvis (c) show multiple areas of increased FDG uptake. (d) Maximum intensity projection reconstruction of CT attenuation–corrected PET image data shows extensive metastases in the liver, bones (left clavicle, both scapulae, sternum, ribs, cervical spine, thoracolumbar spine, pelvis, and both femora), and lymph nodes (axillary, neck, aortocaval, and portacaval).
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Figure 8c. Extensive metastatic disease at PET/CT performed for pretreatment staging of invasive ductal carcinoma in a 48-year-old woman. (a–c) Axial fused PET/CT images of the upper thorax (a), abdomen (b), and pelvis (c) show multiple areas of increased FDG uptake. (d) Maximum intensity projection reconstruction of CT attenuation–corrected PET image data shows extensive metastases in the liver, bones (left clavicle, both scapulae, sternum, ribs, cervical spine, thoracolumbar spine, pelvis, and both femora), and lymph nodes (axillary, neck, aortocaval, and portacaval).
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Figure 8d. Extensive metastatic disease at PET/CT performed for pretreatment staging of invasive ductal carcinoma in a 48-year-old woman. (a–c) Axial fused PET/CT images of the upper thorax (a), abdomen (b), and pelvis (c) show multiple areas of increased FDG uptake. (d) Maximum intensity projection reconstruction of CT attenuation–corrected PET image data shows extensive metastases in the liver, bones (left clavicle, both scapulae, sternum, ribs, cervical spine, thoracolumbar spine, pelvis, and both femora), and lymph nodes (axillary, neck, aortocaval, and portacaval).
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The prevalence of distant metastases increases with an increase in the stage of the primary tumor at diagnosis, and it is relatively uncommon for a distant metastasis to be diagnosed in patients with early-stage breast cancer (stage I or II) at the time of diagnosis. Therefore, FDG PET/CT is likely to be more useful as a screening test for distant metastases in patients with an advanced stage of breast cancer than in those with an early stage.
Treatment Monitoring
Neoadjuvant chemotherapy is often used in the management of large, locally advanced primary breast cancers. A regimen of anthracycline and cyclophosphamide or of cyclophosphamide, methotrexate, and 5-fluorouracil is usually used for neoadjuvant chemotherapy. Preoperative chemotherapy is administered to reduce the size of the primary breast cancer before surgery, but the response to chemotherapy is variable. Knowledge about the effects of treatment is critical for determining whether the current treatment should be continued, stopped, or changed to a more aggressive regimen.
FDG PET is valuable for monitoring the effects of chemotherapy (29,30). Clinical examination and mammography are of limited use for monitoring the treatment response because of the difficulty in distinguishing fibrosis from residual tumor. PET can demonstrate changes in tumor metabolism before morphologic changes occur, so unresponsive tumors can be identified quickly. The uptake of FDG in a tumor after chemotherapy is predictive of the response to therapy; a treatment-induced reduction in metabolic activity correlates with a positive clinical response (Figs 9, 10) (31,32). By directly depicting metabolic and anatomic changes, PET/CT helps improve the accuracy of evaluations of treatment response beyond that achievable with PET alone.
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Figure 9a. Initial and follow-up imaging of recurrent invasive ductal carcinoma in a 60-year-old woman with a palpable right breast mass after a left total mastectomy. (a) Initial US image shows an irregular hypoechoic mass (arrows) in the right breast. The mass was diagnosed on the basis of US-guided biopsy as invasive ductal carcinoma. Because of the patient’s generally poor clinical condition, chemotherapy was administered. (b) Pretreatment coronal PET/CT image shows increased FDG uptake (maximum SUV, 8.7) indicative of hypermetabolism in the lesion (arrow). (c) Posttreatment coronal PET/CT image shows decreased FDG uptake (maximum SUV, 5.6) indicative of a chemotherapy-induced reduction in metabolic activity in the tumor (arrow).
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Figure 9b. Initial and follow-up imaging of recurrent invasive ductal carcinoma in a 60-year-old woman with a palpable right breast mass after a left total mastectomy. (a) Initial US image shows an irregular hypoechoic mass (arrows) in the right breast. The mass was diagnosed on the basis of US-guided biopsy as invasive ductal carcinoma. Because of the patient’s generally poor clinical condition, chemotherapy was administered. (b) Pretreatment coronal PET/CT image shows increased FDG uptake (maximum SUV, 8.7) indicative of hypermetabolism in the lesion (arrow). (c) Posttreatment coronal PET/CT image shows decreased FDG uptake (maximum SUV, 5.6) indicative of a chemotherapy-induced reduction in metabolic activity in the tumor (arrow).
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Figure 9c. Initial and follow-up imaging of recurrent invasive ductal carcinoma in a 60-year-old woman with a palpable right breast mass after a left total mastectomy. (a) Initial US image shows an irregular hypoechoic mass (arrows) in the right breast. The mass was diagnosed on the basis of US-guided biopsy as invasive ductal carcinoma. Because of the patient’s generally poor clinical condition, chemotherapy was administered. (b) Pretreatment coronal PET/CT image shows increased FDG uptake (maximum SUV, 8.7) indicative of hypermetabolism in the lesion (arrow). (c) Posttreatment coronal PET/CT image shows decreased FDG uptake (maximum SUV, 5.6) indicative of a chemotherapy-induced reduction in metabolic activity in the tumor (arrow).
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Figure 10a. Pretreatment staging and follow-up imaging of non-Hodgkin lymphoma in a 32-year-old woman. (a) Axial PET/CT image shows a hypermetabolic (maximum SUV, 21.0) lesion (arrow) in the right breast. US-guided biopsy revealed lymphomatous involvement of the right breast. (b) Axial PET/CT image, obtained after chemotherapy, shows a lessening of lymphomatous involvement.
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Figure 10b. Pretreatment staging and follow-up imaging of non-Hodgkin lymphoma in a 32-year-old woman. (a) Axial PET/CT image shows a hypermetabolic (maximum SUV, 21.0) lesion (arrow) in the right breast. US-guided biopsy revealed lymphomatous involvement of the right breast. (b) Axial PET/CT image, obtained after chemotherapy, shows a lessening of lymphomatous involvement.
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Detection of Recurrences
The accurate staging of local, regional, and distant recurrences after initial diagnosis and treatment is critical for therapeutic planning. In general, systemic therapy is used at almost all disease stages; however, isolated local-regional disease or a single site of metastatic recurrence is also treated with surgery and radiation therapy. After treatment, follow-up examinations are required for the early detection and accurate staging of recurrences.
FDG PET has high accuracy for the diagnosis of recurrent or metastatic breast cancer (33). Because FDG PET provides functional information, it often complements conventional imaging modalities, which are more dependent on morphologic changes to depict disease recurrence. FDG PET is particularly useful for discriminating between viable tumor and posttherapy changes such as necrosis or fibrotic scarring in patients with equivocal results of anatomic imaging. FDG PET also is useful in patients in whom the only indicator of cancer recurrence is an increase in the serum levels of tumor markers such as carcinoembryonic antigen or CA 15-3 antigen (Fig 11) (34,35).
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Figure 11. Extensive metastatic disease at PET/CT in a 38-year-old woman with elevated blood serum levels of tumor markers after a left total mastectomy for invasive ductal carcinoma. Axial fused PET/CT images at progressively lower levels (left and bottom) show multiple areas of increased FDG uptake. Maximum intensity projection reconstruction of CT attenuation–corrected PET image data (right) shows multiple metastases in the right lower internal jugular, right supraclavicular, paratracheal, internal mammary, and tracheobronchial lymph nodes; the left adrenal gland; and the left pubic bone and right acromion.
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Nevertheless, FDG PET is of limited use for the follow-up of breast cancer patients. Its disadvantages include a relatively low rate of detection of bone metastases, especially those of the osteoblastic subtype (36), and a relatively high rate of false-positive results because of FDG uptake in muscle, in areas of inflammation, in the blood pool (the great vessels), and in the bowel. PET/CT can help overcome these limitations. Osteoblastic, sclerotic lesions are readily identified on CT images even when PET findings are negative, and lesions in which uptake is slight can be localized and differentiated from areas of normal physiologic uptake. Integrated PET/CT in breast cancer patients has been shown to improve restaging accuracy over that possible with PET alone, through the accurate localization of functional data on anatomic CT images (6).
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Limitations of FDG PET/CT for Breast Cancer Evaluation
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False-Positive Uptake
FDG is not a tumor-specific substance. Increased FDG accumulation may be observed in a variety of benign entities and in some physiologic conditions, which may yield false-positive findings and reduce the accuracy of the technique. To interpret FDG PET/CT findings accurately, one must be familiar with the normal physiologic distribution of the tracer, frequently encountered physiologic variants, and benign pathologic causes of FDG uptake that may be confused with malignant neoplasms. There is usually less uptake in normal tissues and benign conditions than in neoplastic tissues. However, there is clearly some overlap in the degree of uptake, and, in some cases, normal uptake might even exceed neoplastic uptake.
FDG may accumulate in areas affected by various nonneoplastic pathologic conditions, including acute and chronic infections (Fig 12) (37). At sites of infection or inflammation, the glycolytic metabolism is elevated because of the leukocytic infiltration associated with inflammatory processes, with a consequent increase in FDG uptake (38).
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Figure 12a. False-positive finding at PET/CT during preoperative staging of rectal cancer in a 47-year-old woman. (a) Axial PET/CT image shows a hypermetabolic (maximum SUV, 5.7) lesion (arrow) in the right breast, a finding that was believed to represent breast cancer. (b) Subsequent US image shows an oval circumscribed mass (arrows) in the right subareolar area. A US-guided biopsy was performed, and the mass was diagnosed on the basis of pathologic analysis as a chronic abscess.
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Figure 12b. False-positive finding at PET/CT during preoperative staging of rectal cancer in a 47-year-old woman. (a) Axial PET/CT image shows a hypermetabolic (maximum SUV, 5.7) lesion (arrow) in the right breast, a finding that was believed to represent breast cancer. (b) Subsequent US image shows an oval circumscribed mass (arrows) in the right subareolar area. A US-guided biopsy was performed, and the mass was diagnosed on the basis of pathologic analysis as a chronic abscess.
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Increased FDG uptake may be observed in patients who recently underwent surgery or radiation therapy. Radiation therapy may cause inflammation in normal structures. After surgery, even in the absence of infection, healing involves an inflammatory reaction (Fig 13). Leukocytic infiltration with a consequent increase in FDG uptake is present in the granulation tissue associated with wound repair and the resorption of necrotic debris and hematoma (37,39). Uniform diffuse increased uptake in bone marrow also can be seen during bone marrow recovery after chemotherapy, but this usually resolves by 1 month after therapy (40).
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Figure 13a. False-positive finding at PET/CT during restaging and follow-up after breast-conserving surgery and radiation therapy for invasive ductal carcinoma in a 53-year-old woman. (a) Mammogram shows an area of postoperative and radiation-induced change (arrow) in the outer region of the left breast. (b) Axial PET/CT image shows a focus of FDG uptake (maximum SUV, 3.1) (arrow) in the upper outer region of the left breast. A US-guided biopsy was performed, and pathologic analysis showed no evidence of a recurrence.
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Figure 13b. False-positive finding at PET/CT during restaging and follow-up after breast-conserving surgery and radiation therapy for invasive ductal carcinoma in a 53-year-old woman. (a) Mammogram shows an area of postoperative and radiation-induced change (arrow) in the outer region of the left breast. (b) Axial PET/CT image shows a focus of FDG uptake (maximum SUV, 3.1) (arrow) in the upper outer region of the left breast. A US-guided biopsy was performed, and pathologic analysis showed no evidence of a recurrence.
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False-Negative Uptake
Among the many factors that affect the detection of breast cancers at PET, small tumor size (< 1 cm) and less aggressive histologic subtype (eg, tubular carcinoma, carcinoma in situ) are strong predictors of false-negative findings (41). Given the limited spatial resolution of FDG PET, its sensitivity depends largely on the lesion size. PET/CT does not reliably depict lesions smaller than 1 cm in diameter. In addition, there is greater heterogeneity with regard to the degree of FDG uptake between the different histologic subtypes of breast cancer than between other malignant tumors. Slow-growing cancers such as tubular carcinoma and noninvasive cancers such as ductal or lobular carcinoma in situ may be overlooked on FDG PET images (Figs 14, 15) (15, 17,18,20–22).
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Figure 14a. False-negative finding at PET/CT during staging of ovarian cancer in a 56-year-old woman. (a) Mammogram of the left breast, obtained before the administration of hormonal therapy, shows a cluster of pleomorphic and amorphous microcalcifications (arrows). The pathologic diagnosis after a wire localization biopsy was ductal carcinoma in situ. (b) Axial PET/CT image shows no corresponding area of increased FDG uptake.
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Figure 14b. False-negative finding at PET/CT during staging of ovarian cancer in a 56-year-old woman. (a) Mammogram of the left breast, obtained before the administration of hormonal therapy, shows a cluster of pleomorphic and amorphous microcalcifications (arrows). The pathologic diagnosis after a wire localization biopsy was ductal carcinoma in situ. (b) Axial PET/CT image shows no corresponding area of increased FDG uptake.
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Figure 15a. False-negative finding at PET/CT during restaging of ovarian cancer in a 63-year-old woman. (a) Image obtained at US, which was performed for evaluation of a palpable lesion in the left breast, shows an approximately 0.8-cm-diameter irregular mass (arrows) in the right breast. The diagnosis of the right breast lesion, based on pathologic analysis after a US-guided biopsy, was tubular carcinoma. (b) Axial PET/CT image shows no hypermetabolic lesion.
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Figure 15b. False-negative finding at PET/CT during restaging of ovarian cancer in a 63-year-old woman. (a) Image obtained at US, which was performed for evaluation of a palpable lesion in the left breast, shows an approximately 0.8-cm-diameter irregular mass (arrows) in the right breast. The diagnosis of the right breast lesion, based on pathologic analysis after a US-guided biopsy, was tubular carcinoma. (b) Axial PET/CT image shows no hypermetabolic lesion.
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Detection of an Unexpected Primary Cancer
The detection of an unexpected malignant lesion has clinical significance not only for asymptomatic individuals but also for patients with known malignant disease. Whole-body FDG PET/CT may be used to survey the entire body. In one study, the prevalence of pathology-proved additional primary malignancies at PET/CT performed for known or suspected malignancies was 1.2% (Figs 16, 17) (42). Unexpected focal hypermetabolic activity in the breast in patients undergoing PET/CT for reasons other than breast cancer may represent infiltrating ductal carcinoma (43). Further work-up for diagnosis of the additional lesion is essential because patient management frequently is altered by the new diagnosis. Lesions newly detected at PET/CT are often at an early stage and have an excellent likelihood of cure if they are treated promptly.
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Figure 16a. Unexpected primary breast cancer detected at PET/CT performed for restaging of rectal cancer in a 60-year-old woman. (a) Axial PET/CT image shows a hypermetabolic (maximum SUV, 10.4) lesion (arrow) in the right breast. Subsequent mammography and US were performed. (b) US image shows the lesion (arrows), which was diagnosed at pathologic analysis after US-guided biopsy as apocrine carcinoma of the breast.
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Figure 16b. Unexpected primary breast cancer detected at PET/CT performed for restaging of rectal cancer in a 60-year-old woman. (a) Axial PET/CT image shows a hypermetabolic (maximum SUV, 10.4) lesion (arrow) in the right breast. Subsequent mammography and US were performed. (b) US image shows the lesion (arrows), which was diagnosed at pathologic analysis after US-guided biopsy as apocrine carcinoma of the breast.
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Figure 17a. Unexpected primary cancer detected at PET/CT performed for restaging of invasive ductal carcinoma in a 62-year-old woman after a right total mastectomy. (a) Axial PET/CT image shows a hypermetabolic (maximum SUV, 5.5) lesion (arrow) in the right lobe of the thyroid gland. (b) US image shows a hypoechoic nodule (arrow) in the right thyroid lobe. A US-guided fine needle aspiration biopsy was performed. The pathologic diagnosis was thyroid papillary carcinoma.
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Figure 17b. Unexpected primary cancer detected at PET/CT performed for restaging of invasive ductal carcinoma in a 62-year-old woman after a right total mastectomy. (a) Axial PET/CT image shows a hypermetabolic (maximum SUV, 5.5) lesion (arrow) in the right lobe of the thyroid gland. (b) US image shows a hypoechoic nodule (arrow) in the right thyroid lobe. A US-guided fine needle aspiration biopsy was performed. The pathologic diagnosis was thyroid papillary carcinoma.
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FDG PET/CT in Benign Breast Disease
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In the presence of benign diseases such as fibro-adenoma, breast tissue usually shows low FDG uptake (Fig 18). However, an increased accumulation of FDG in the breast may be observed in some cases (eg, in the presence of fibrocystic change, atypical ductal hyperplasia, ductal ectasia, and phyllodes tumor) and may lead to false-positive findings (Fig 19) (21,44).
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Figure 18a. Fibroadenoma in the left breast of a 43-year-old woman. (a) US image obtained for routine monitoring of a previously diagnosed fibroadenoma shows a well-circumscribed oval mass (arrow). (b) Axial PET/CT image shows no significant uptake (maximum SUV, 1.6) in the mass (arrow).
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Abstract
LEARNING OBJECTIVES FOR TEST...
