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Breast Cancer

Current Status of Positron Imaging for Breast Cancer 
  Submitted By: Jacqueline Brunetti

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Current Status of Positron Imaging for Breast Cancer


Article Authored by: Jacqueline Brunetti, M.D.



Positron emission tomography, PET,is currently accepted to be the most accurate way to stage and monitor many types of cancer. PET is a Nuclear Medicine imaging technique that uses very short-lived radioactive compounds that localize in cancer cells. Recent advances in molecular biology research have identified many abnormalities of cellular function in tumors. Cancer cells have alterations in the normal metabolism of the sugar, glucose, and have increased glucose uptake and decreased glucose clearance. Glucose can be bound to the positron 18-F to make a compound 18 F-fluorodeoxyglucose, FDG. When injected into a patient's blood stream, FDG is taken up by the cancer cells at a more rapid rate than normal cells and allows cancers to be seen as “hot spots” on the PET scan. A typical PET scan usually images the body from the head to the upper thighs. Because the brain uses glucose for metabolism, high background activity can mask small lesions, and so, PET has limited value for diagnosing brain metastases.
Blood sugar level affects tumor uptake on PET scans. With high blood glucose, tumor uptake of FDG may be decreased and so patients are asked to fast before the scan. Also, since muscles also use glucose for metabolism, patients are required to lie still for about 60-90 minutes after FDG injection. It is also necessary to curtail any vigorous exercise, just as jogging or weight lifting, for at least 48 hours prior to a PET scan as the recovering muscles will continue to take up glucose for about 24 hours.
Scanners are now available that can perform both PET and CT scans in the same imaging session. The images that are obtained can be overlaid or fused so the functional information of the PET scan can be accurately localized on the high-resolution anatomic images of the CT scan. Fusion imaging performed on these hybrid scanners has been shown to improve whole body scan diagnostic accuracy.

BREAST CANCER DIAGNOSIS:

Although positron imaging is very useful in identifying recurrent of metastatic disease, Medicare coverage for diagnosis of primary breast tumors is currently not approved by HCFA. Tumor size and cell type are factors that effect PET scan accuracy. Although accuracy in detecting tumors larger than 2cm is high, PET may miss approximately one third of invasive cancers smaller that 1 centimeter. PET is more likely to identify invasive ductal carcinoma, to miss invasive lobular carcinomas, and is not helpful for identification of non-invasive tumors. Although the basic mechanism of uptake is via glucose metabolism, other factors that result in this variation in FDG uptake in breast tumors have not been clearly identified. When positive, however, the intensity of PET uptake in a primary breast tumor has been shown to correlate with the degree of tumor aggressiveness.
Care must be taken in interpreting PET scans of patients after biopsy of surgery, as sites of inflammation of infection will also display increased uptake of FDG. With these limitations, PET is not useful as a screening tool. It may, however, provide some benefit when used for problem solving. For example, the value of mammography is often limited after breast augmentation, and in this situation, PET might offer some advantage in screening for cancer. Combining PET and dynamic MRI information in assessment of breast lesions found on mammography may decrease the number of biopsies of benign lesions, as the high specificity of PET complements the high sensitivity of dynamic breast MRI. Currently, a few research centers are evaluating dedicated positron emission mammography devices that may potentially improve identification of small breast cancers.




Figure 1. Normal PET scan. Regions of most intense normal uptake are in the brain, the heart and in the kidneys and bladder.





(Fig. 2)Red arrows indicates a metastatic lesion in the spine in a patient with breast cancer. Fusion image shows the exact location of the positive region seen on the PET scan.





Figure 3: Arrow indicates a focus of positive PET uptake in an invasive ductal cancer.





Figure 4. Arrow shows a metastatic internal mammary lymph node.


STAGING:

Axillary lymph node dissection (ALND) is an accepted as part of the surgical staging of breast cancer. At initial diagnosis of breast cancer, the presence of tumor in axillary lymph nodes and the number of positive nodes govern prognosis and therapy choice. Sentinel node mapping and biopsy is now the procedure of choice for patient's who are ALND candidates. This procedure involves an injection into the breast of a small amount of radioactive material that is then taken up by the lymphatic system. The radioactivity will then travel to the lymph nodes located under the arm. At surgery, the surgeon uses a probe to locate and biopsy these radioactive lymph nodes. If the nodes are negative for tumor, radial ALND does not need to be performed.
Due to the same reasons as discussed above regarding small breast tumors, PET scan has not replaced sentinel node mapping and biopsy. Moreover, no imaging technique is capable of identifying microscopic tumor spread. When positive, however, PET is very specific for the presence of tumor in the axilla. It has been suggested that if pre-operative PET scan is positive in axillary nodes that the extra intraoperative procedure of sentinel node mapping and lymph node biopsy can be deferred in patients who are candidates for axillary node dissection. Although results in the axilla are unsatisfactory, PET is more accurate that CT scan for identification of lymph node spreads in the mediastinum, the area around the heart and great vessels and internal mammary nodal regions that are located at either side of the breast bone.

RESTAGING:

Accuracy in staging and early identification of recurrent tumor is critical for therapy choice. Keeping in mind the limitations of PET with very small lesions, whole-body PET scan, nevertheless, is an excellent method for follow-up imaging of breast cancer patients. PET is more accurate than bone scan in patients who have predominantly lytic, or destructive bone metastases. When bone lesions are dense or blastic, they may be better seen on conventional bone scan. In studies evaluating asymptomatic patients with rising serum tumor markers, PET has an accuracy of 87-90% in detecting sites of metastatic disease. Furthermore, in patients with negative serum tumor markers but suspicious clinical findings, PET scanning appears to be a more reliable than conventional imaging for identifying relapsed tumor.

MONITOR THERAPY:

Uptake of FDG in metastases can be evaluated after chemotherapy or radiation for assessment of therapy response. Some researchers have shown that it is possible to identify patients who will respond to chemotherapy if PET scanning is performed immediately after a first cycle of chemotherapy. Responders will show a rapid decline in FDG uptake in metastases, whereas, non-responders will show little or no change in FDG uptake.
PET and combined PET/CT scanners are also being used to direct radiation therapy in patients who have localized metastatic disease in areas such as the chest wall or in bone.




Figure 5. Image A shows positive uptake on PET scan (left) in the sternum and in mediastinal nodes in a patient with metastatic breast cancer. Image B is the same patient after chemotherapy and radiation showing complete response to treatment.


CONCLUSION:

PET imaging is a clear advance in the approach to staging and monitoring breast cancer. Positron imaging offers better accuracy than conventional imaging in the identification of metastatic disease both in the initial staging of breast cancer and in follow-up. In the future, further refinements in scanner technology and new radiopharmaceuticals will likely result in better identification of smaller lesions. Dedicated breast PET/CT or PET/Mammography units show promise in improved detection in primary breast cancer, while also providing a method for image guided biopsy. Ongoing research in the molecular basis of cancer will likely result in new agents that may better identify tumors currently not well imaged by FDG. Potentially, molecular therapies that target specific cell receptors or processes may be tagged with a positron and imaged, thereby allowing not only imaging but also treatment.

Jacqueline Brunetti, M.D.
Medical Director Department of Radiology, Holy Name Hospital
Associate Professor of Clinical Radiology, Columbia University
Teaneck, New Jersey 07666 


 


Additional Authors:  

Works Cited:  
  Wu D, G SS Positron Emission Tom,ography in Diagnosis and Management of Invasive Breast Cancer: Current Status and Future Perspectives. Clinical Breast Cancer 2003;4(1)S55-S63.
Wahl RL, Helvie MA, et al. Detection of Breast Cancer in Women After Augmentation Mammoplasty Using Fluorine-18-Fluorodeoxyglucose-PET. J Nucl Med 1994;35(5):872-875.
Walter C, Scheidhauer WC, et al. Clinical Diagnostic Value of Preoperative MR Mammography and FDG-PET in suspicious breast lesions. Eur Radiol 2003;13(7):1651-1666.
Levine EA, Freimanis RI, et al. Positron Emission Mammography: Initial Clinical Results. Ann Surg Oncol 2003;10(1):86-91
Barranger E, Grahek D, et al. Evaluation of Fluorodeoxyglucose Positron Emission Tomography in the Detection of Axillary Lymph Node Metastases in Patients With Early- Stage Breast Cancer. Ann Surg Oncol2003;10(6):622-627.
Gennari A, Donati S, et al. Role of 2-[18F]-Fluorodeoxyglucose (FDG) Positron Emission Tomography in the Early Assessment of Response to Chemotherapy in Metastatic Breast Cancer. Clinical Breast Cancer 2000;1(2):156-161.


 
 


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