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Breast Imaging |
1 Departments of Radiology (P.B.H., D.A.M., K.R.M., A.A.C., C.E.H.)
2 Radiation Oncology (M.M.A.S.)
3 Division of Medical Oncology (G.K.E., J.R.G.)
4 Department of Surgery (R.E.M.), University of Washington School of Medicine, Box 356113, Room NN203, 1959 NE Pacific St, Seattle, WA 98195-7115.
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Abstract |
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 TOP Abstract IntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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MATERIALS AND METHODS: Upper-body FDG PET and axillary and supraclavicular MR imaging were performed in 10 patients (age range, 45–71 years) with clinical findings suggestive of breast cancer metastases. Medical records were reviewed retrospectively. Imaging findings were correlated with clinical data and follow-up findings in all patients. Surgical findings were available in four patients.
RESULTS: Nine patients had local-regional breast cancer metastases. MR imaging was diagnostic for tumor in five patients and was indeterminate in four patients with axillary or chest wall metastases. With FDG PET, metastatic tumor was positively identified in all nine patients. MR imaging was useful for determining the relationship of metastatic tumor to axillary and supraclavicular neurovascular structures. FDG PET helped confirm metastases in patients with indeterminate MR imaging findings and depicted unsuspected metastases outside the axilla.
CONCLUSION: MR imaging and FDG PET are complementary in detecting and characterizing local-regional breast cancer metastases. Combined FDG PET and MR imaging provide useful treatment-planning data for patients clinically suspected of having recurrent axillary or supraclavicular breast cancer.
Index terms: Axilla, 07.12163, 07.33 • Breast neoplasms, emission CT (ECT), 07.12163, 09.12163 • Breast neoplasms, metastases, 07.33, 09.33 • Breast neoplasms, MR, 07.1214, 09.1214 • Fluorine, 07.12163 • Glucose, 07.12163
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Introduction |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Physical examination in these patients is frequently limited by the delayed effects of surgery and radiation therapy, which include restriction of shoulder motion, pain in the irradiated breast or chest wall, scar tissue formation, radiation-induced fibrosis, lymphedema, and arm weakness (7). Moreover, the signs and symptoms of local-regional recurrence of breast cancer often overlap with the side effects of treatment, including peripheral neuropathy, brachial plexopathy, arm pain, and lymphedema (8,9).
The diagnosis of local-regional recurrence of breast cancer usually is an indication for renewed treatment with irradiation for control of local disease and systemic chemotherapy for presumed occult disseminated metastases. If invasion of neurovascular structures is not extensive, tumor masses in the axilla and chest wall may be surgically resected, with improved control of local-regional disease and decreased morbidity (10–14). Alternatively, if recurrent cancer can be excluded as a cause of symptoms, the presumed side effects of therapy can be treated symptomatically.
Exploratory surgery of the axilla has been used to confirm or exclude malignant disease in patients with breast cancer who have brachial plexopathy, but exploration may yield inconclusive results and sometimes worsens the effects of axillary scarring (6). Although advanced breast cancer with axillary vein or artery encasement may be amenable to palliative surgery, invasion of the brachial plexus generally precludes gross total resection. Because of the frequent ambiguity of the results from clinical evaluation and the potential for unnecessary or nonbeneficial axillary exploration, a reliable noninvasive method for the diagnosis of regionally metastatic breast cancer is desirable, particularly when surgical resection is contemplated.
Magnetic resonance (MR) imaging with high-detail techniques based on the use of specially designed phased-array surface coils is the modality of choice for evaluating the brachial plexus (8,15,16). MR imaging has been used successfully by several investigators to detect and characterize regionally recurrent breast cancer (15,17,18). MR imaging of the brachial plexus with high-detail techniques and specially designed surface coils has resulted in better direct imaging of the brachial plexus and surrounding structures, including characterization of nerve branches (18–20). However, even state-of-the-art MR imaging can result in indeterminate or nondiagnostic findings; the signal characteristics and morphologic appearance of diffusely infiltrating tumor sometimes overlap with those of radiation- or surgery-related scarring (18).
Positron emission tomography (PET) with the radiolabeled glucose analogue 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) is a technique based on the presence of altered metabolism within neoplastic tissues; FDG PET has been shown to be useful in the detection of a wide range of tumors, including breast cancer (21–30). Despite the high contrast between FDG uptake by tumors and that by most benign tissues, the limited spatial resolution of PET hinders the use of FDG PET to detect small tumors (22) and prohibits precise determination of the relationship of tumor masses to the chest wall and regional neurovascular structures.
Our hypothesis in this study is that MR imaging and FDG PET are complementary in the staging of recurrent axillary breast cancer. In particular, surface coil MR imaging can be used to delineate detailed anatomy, including tumor involvement of the axillary neurovascular structures, but the importance of abnormalities can be difficult to determine. Although FDG PET cannot resolve detailed axillary anatomy, it can clarify the nature of MR imaging abnormalities as metabolically active tumor versus scarring from previous treatment. FDG PET can also be used to identify sites of disease outside the suspected axillary recurrence.
We present a retrospective analysis of our initial findings with this combined approach. The purpose of this analysis was to examine the performance and potential clinical effects of combined FDG PET and MR imaging in patients who have disturbing but inconclusive clinical features of recurrent breast cancer in the axilla and surrounding regions.
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MATERIALS AND METHODS |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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All patients underwent both MR imaging of the axilla and supraclavicular region and FDG PET of the neck and thorax, with the two studies performed within 36 days of each other (mean interval between studies, 14 days; range, 0–35 days). Patients were referred for MR imaging as part of the clinical routine for patients with symptoms suggestive of recurrent axillary breast cancer. Patients underwent PET as part of a study of the application of FDG PET to diagnosis in oncology. All patients signed informed consent for the PET study under a protocol approved by the University of Washington Human Subjects Committee. No patients were excluded because of technically inadequate examinations.
The medical records of all patients were reviewed retrospectively. Surgical confirmation was available in four patients. In an additional five patients, follow-up FDG PET studies were performed to determine the change over time in the extent and metabolic activity of detected lesions. Clinical information was available for all patients, with follow-up ranging from 2 months to 2 years (mean, 11.8 months). Four patients died during the follow-up period. The clinical data are summarized in Table 1.
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Three patients had already developed symptoms suspicious for regionally advanced breast cancer at the time of presentation and initial staging. All three of these patients experienced arm pain or weakness or both; one also had upper-extremity lymphedema.
In the remaining seven patients, the time between initial diagnosis and the development of symptoms and signs suggestive of axillary recurrence ranged between 1 month and 10 years (mean, 5.1 years). Six of these patients complained of arm or shoulder pain or both; four also had symptoms suggestive of nerve dysfunction, including arm weakness, sensory loss, or painful dysesthesias; three also had developed upper-extremity lymphedema. The seventh patient developed upper-extremity lymphedema alone, without arm pain or weakness. The histologic diagnosis was infiltrating carcinoma in nine patients; there was one infiltrating lobular carcinoma.
Imaging Protocols
PET imaging.—FDG was produced at our institution by means of a standard technique that uses nucleophilic fluorination (31). The FDG radiochemical purity was 95%, and its specific activity was more than 47 GBq/mmol. All patients fasted for at least 4 hours before undergoing FDG PET. Blood glucose measurements were obtained before FDG injection to identify hypoglycemia. No patient had a measured blood glucose level of less than 80 mg/100 mL or more than 140 mg/100 mL at the time of injection. A dose of 260–370 MBq (7–10 mCi) of FDG was injected into an arm vein through a peripheral intravenous or central venous catheter on the side contralateral to the site of suspected tumor involvement. Emission scans were obtained beginning at 45–60 minutes after the start of the injection of FDG.
Imaging was performed with a commercially available whole-body PET scanner (Advance; GE Medical Systems, Milwaukee, Wis) that was operating in the high-sensitivity mode. PET was performed from the neck to the upper abdomen. Data were acquired two-dimensionally with an axial field of view of 15 cm, with 10-minute emission and 15-minute transmission scans obtained for each axial field of view. Thirty-five axial sections were acquired per axial field of view; three fields were acquired to yield a total axial extent of 45 cm.
Attenuation-corrected emission data were reconstructed with filtered back-projection with a Hanning filter, which yielded a reconstructed in-plane spatial resolution of 10–12 mm (32,33). Radioactive decay was corrected for with the time of tracer injection as a reference. Images were normalized to the injected dose and body weight, which resulted in regional standardized uptake values (SUVs): SUV = A/(ID/BW), where A is the tissue tracer uptake in microcuries per gram, ID is the injected dose in millicuries, and BW is the body weight in kilograms. Standardized uptake value images were reformatted into 12-mm-thick coronal planes. Axial images were reviewed as necessary to evaluate confusing or questionable findings seen on the coronal images.
MR imaging.—MR imaging was performed with a 1.5-T superconducting magnet (Signa; GE Medical Systems). Detailed images of the supraclavicular and axillary regions were obtained with a specialized phased-array surface coil that was custom-built in our laboratory and designed specifically for imaging of the brachial plexus and regional supraclavicular-axillary structures (34).
After a coronal localizing image of the upper thorax and shoulders was obtained by using a body coil, detailed T1-weighted spin-echo (SE) images (600/10 [repetition time msec/echo time msec]; field of view, 26 cm; section thickness, 4 mm; matrix size, 512 x 256; two signals acquired) and short inversion time inversion-recovery (STIR) images (4,000/34–43/160 [repetition time msec/echo time msec/inversion time msec]; field of view, 26 cm; section thickness, 4 mm; matrix size, 512 x 256; two signals acquired) were obtained in coronal and oblique sagittal orientation perpendicular to the long axis of the trunks and divisions of the brachial plexus. In selected patients, axial T1-weighted and STIR images were obtained with similar parameters.
Patients with findings suspicious for recurrent tumor were also studied after the injection of gadopentetate dimeglumine (0.1 mmol/kg; Magnevist; Berlex Laboratories, Wayne, NJ) by using a fat-suppressed SE T1-weighted sequence (600–750/10–16; field of view, 26 cm; section thickness, 4 mm; matrix size, 512 x 256; two signals acquired) in coronal and oblique sagittal planes.
Image Interpretation
The findings from PET examinations were interpreted prospectively by a nuclear medicine physician experienced in clinical PET imaging (D.A.M.). By using a combination of qualitative visual image interpretation and comparison of standardized uptake values to normal structures, radiotracer distribution in the axilla, breast, and chest was characterized as either abnormal or normal.
For each focus of abnormal uptake, the standardized uptake value of the maximum pixel in the focus was recorded. This value was not used to provide a cutoff for benign versus malignant lesions but to facilitate a comparison with uptake in normal structures. This value is also useful in following changes in uptake in serial scans of patients undergoing treatment.
The findings from MR examinations were interpreted by a single neuroradiologist (K.R.M.) experienced with MR imaging of the brachial plexus. Tumor spread or metastasis in the axilla or supraclavicular region was diagnosed with MR imaging if masslike soft-tissue accumulations were present, with or without abnormal soft-tissue enhancement. Indeterminate findings for the presence of tumor included ill-defined increased STIR signal intensity or nonspecific tissue enhancement when these occurred in the absence of a mass.
The diagnosis of vascular or brachial plexus invasion was made when encasement or obliteration of neurovascular structures was present. When a definite fat plane was present separating a tumor mass and the neurovascular structures of the axilla and supraclavicular region, the study was interpreted as showing no evidence of neurovascular encasement or invasion. If an intervening fat plane was absent but there were no definite signs of neurovascular encasement, the study was interpreted as showing probable neurovascular invasion. The presence of increased STIR signal intensity within nerves of the axilla was interpreted as consistent with radiation-induced plexitis or diffuse tumor invasion when no accompanying mass was present.
PET and MR images were interpreted initially without information from the complementary imaging examination. After initial interpretation, cross-correlation between the results of the two imaging modalities was performed (D.A.M., K.R.M.), and a final diagnosis was made by consensus. For comparison of images, there was a high reliance on printed coronal PET images and coronal MR images, with subjective coregistration of anatomic landmarks.
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RESULTS |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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In two (patients 8 and 9) of these four patients, abnormal MR signal intensity involved the brachial plexus, and surgery was deferred. Axillary and chest wall resections were performed on the other two patients in whom no evidence of brachial plexus invasion was seen on MR images. MR imaging was used to predict axillary vein encasement in patient 2, but the surgical finding of brachial plexus and axillary artery encasement showed that the extent of diffusely infiltrating tumor in this patient had been underestimated with MR imaging; invasion of the brachial plexus prevented gross total resection (Fig 3). In the other patient (patient 6), surgical findings were consistent with the imaging diagnosis of axillary vein encasement without brachial plexus involvement.
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One patient (patient 8) has shown a complete clinical response to systemic chemotherapy, and repeat PET imaging performed 4 months after the reinstatement of therapy showed no evidence of residual metabolically active tumor. The condition of three patients (patients 4, 7, and 10) has remained clinically stable while they are undergoing chemotherapy or radiation therapy or both, with no evidence of progression of regional or metastatic disease.
Five patients (patients 1, 2, 5, 6, and 9) have shown progression of disseminated metastatic disease; four of these five patients have died of complications of disseminated breast cancer. In the one patient in whom combined PET–MR imaging showed no evidence of recurrent tumor, no clinical evidence of recurrence has been found for 1 year, and the severity of lymphedema has decreased markedly with conservative therapy.
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DISCUSSION |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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In most of our patients, the diagnosis of metastatic disease in the axilla was considered likely by the referring physicians because of symptoms that were suspicious for such disease and because of the combined results of the history, physical examination, and abnormal nerve conduction studies. In these patients, FDG PET alone may have been sufficient to answer the simple clinical question of recurrence. However, the additional information provided by detailed MR imaging was helpful in identifying patients whose condition might be suitable for local surgical resection to control the disease.
Our MR imaging included the use of phased-array coils to improve the signal-to-noise ratio and permit imaging with a 512 x 256 resolution matrix. We used T1-weighted imaging to outline nerve structures and fat, together with STIR imaging to assess abnormal signal intensity changes in the tumor mass or brachial plexus nerves or both. In most patients, postcontrast T1-weighted imaging combined with fat saturation was also performed to help detect the extent of tumor in relation to neural structures.
With these techniques, MR imaging alone would have been sufficient to establish a diagnosis and determine resectability in five patients. In four patients, however, the MR findings were indeterminate, and PET was necessary to definitely confirm the presence of axillary and chest wall tumor.
Chemotherapy or radiation therapy or both were begun in all nine patients in whom recurrent breast cancer was diagnosed. The presence and extent of neurovascular invasion were critical in determining whether tumor masses were surgically resectable; on the basis of the findings from imaging, surgical treatment was attempted in four patients and deferred in five. Potentially morbid treatments were avoided in one patient with negative findings on imaging studies, and conservative therapy has resulted in marked symptomatic relief of lymphedema.
FDG PET also was able to depict unsuspected metastases outside the axilla in five patients. Although the identification of additional foci of metastatic disease with PET did not affect initial treatment (all five would have received chemotherapy anyway), several patients whose condition responded to local therapy for their axillary disease had subsequent progression at another site. The identification of these other sites on the initial PET study facilitated the assessment of the subsequent response to systemic therapy. Systemic therapy would have been difficult to evaluate on the basis of the response of axillary disease because most patients received local therapy for their axillary disease for palliation of symptoms.
In this preliminary retrospective study, we did not evaluate factors such as the interobserver variability of image interpretation, nor did we provide a comparison to other standard staging modalities such as computed tomography (CT). In addition, because in many patients the findings from combined PET–MR imaging suggested that the patients were not surgical candidates, our study is limited by a frequent lack of histologic confirmation of imaging diagnoses. In most patients, however, subsequent progression of local disease and distant metastases has supported the imaging diagnosis of tumor.
The limited usefulness of MR imaging to differentiate diffusely infiltrating cancer from scarring or radiation-induced fibrosis in our patients is similar to that reported by others (18). The additional information provided with FDG PET improved our ability to make a correct positive diagnosis, but accurate identification of neurovascular invasion was imperfect. Of the four patients who underwent surgical exploration and debulking, the extent of disease depicted by MR imaging was correct in three, but in one patient MR imaging yielded an underestimation of the extent of tumor in the axilla and failed to depict the presence of brachial plexus encasement.
Despite this shortcoming, we believe that it is unlikely that any patients with axillary recurrence and no involvement of the brachial plexus and axillary blood vessels were denied effective surgical debulking because they were falsely identified as having neurovascular invasion.
A potential limitation of this approach is the high monetary cost of these imaging modalities and the limited availability of PET and brachial plexus MR coils at most hospitals. We suggest that the cost of these studies is offset by (a) the early identification of patients who may benefit from surgery or radiation therapy or both before the dire consequences of shoulder and neurovascular encasement occur and (b) the avoidance of unnecessary surgery in patients with marked neurovascular invasion by tumor.
Furthermore, the patients in our series are typical of those referred to tertiary cancer-specialty hospitals such as our own, where these modalities often already are available. A rigorous assessment of the cost-effectiveness of this combined approach would require a more detailed prospective study, as well as a comparison with other available lower-cost techniques, such as CT.
In conclusion, MR imaging can provide high-spatial-resolution images of the brachial plexus and axilla, but the accuracy of tumor detection with MR imaging can be limited by the presence of diffusely infiltrating tumor. PET, with the use of quantitative tissue characterization, can be used to detect the extent of disease with potentially more specific tumor identification than is possible with MR imaging and may reveal the presence of unsuspected metastases outside the axilla. Correlation of PET data with the anatomic information derived from MR imaging resulted in data that were helpful in determining the approach to both local and systemic therapy in patients suspected of having recurrent or advanced axillary disease.
In summary, our initial experience suggests that the combination of MR imaging and PET is extremely useful in assessing recurrent axillary breast cancer. Further investigation into the accuracy and clinical value of these imaging techniques is warranted.
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Acknowledgments |
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Footnotes |
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Address reprint requests to D.A.M.
Abbreviations: FDG = 2-[fluorine 18]fluoro-2-deoxy-D-glucose SE = spin echo STIR = short inversion time inversion recovery
Author contributions: Guarantors of integrity of entire study, P.B.H., D.A.M.; study concepts and design, P.B.H., D.A.M., K.R.M.; definition of intellectual content, P.B.H., D.A.M., K.R.M.; literature research, P.B.H., D.A.M.; clinical studies, D.A.M., K.R.M.; data acquisition, P.B.H., A.A.C., D.A.M.; data analysis, P.B.H.; manuscript preparation and editing, P.B.H.; manuscript review, M.M.A.S., G.K.E., J.R.G., C.E.H., R.E.M.
Received March 19, 1998;
revision requested June 5, 1998; revision received August 31, 1998;
accepted October 7, 1998.
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References |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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