| [Objective]1. To acess the value of F-FDG PET/CT in diagnosing breast cancer.2. To evaluate the role of PET/CT in detection of recurrent metastasis, monitoring and restaging on postoperative breast cancer[Materials and Methods]1. Study objective1.1 breast masses group66 patients with breast masses who underwent 18F-FDG PET/CT in Nanfang PET centre, Nanfang Hospital during January 2007 to November 2010 were enrolled in this study aged from 29 to 86 years old, with a mean age of 48.3 years old. All of patients underwent whole body 18F-FDG PET/CT scan. Of the 66 patients,36 were primary breast cancer and 30 were benign diseases. The diagnosis of 36 malignant tumors and 17 benign diseases was established based on the histopathology examination, the diagnosis of 17 benign diseases was established according to B-ultrasound, CT scan, MRI, molybdenum target and clinical follow- up more than 6 months. 1.2 postoperative breast cancer group104 patients after breast surgery who underwent 18F-FDG PET/CT in Nanfang PET centre, Nanfang Hospital during January 2007 to November 2010 were enrolled in this study aged from 27 to 69 years old, with a mean age of 45.2 years old. All of patients underwent whole body 18F-FDG PET/CT scan at least one time. The diagnosis of 13 positive patients in 18F-FDG PET/CT scan were established based on the histopathology examination,99 patients'diagnosis was according to multi-modalities of imaging and cytological examination.The image diagnosis of metastasis was established based on more than twice imaging change:(1) when indicated the metastasis biger or discover another on by B-ultrasound, CT scan and/or SPECT. (2) when indicated the metastasis smaller or disappear in the course of treatment and consistent with better condition. The diagnosis of benign diseases was established according to B-ultrasound, CT scan, MRI, molybdenum target and clinical follow-up more than 6 months.2. Main equipments and imaging agentThe examinations were carried out using a GE Discovery LS PET/CT scanner (GE, Healthcare, and Waukesha, WI). The positron emitter was produced using the cyclotron of PETtracer (GE, Healthcare, Waukesha, WI).The tracer 18F-FDG, was manufactured automated by the tracer synthesis system of FDG Microlab (GE, Healthcare, Waukesha, WI), with a radiochemical purity> 95%.3. Imaging methods and conditionsAll patients and healthy Subjects underwent PET/CT scans after fasting at least 6 hours prior to examination. Patients also received orally 600ml and 200ml of 1.5% diatrizoate meglumine at an hour and 5 minute before the scans.5.5MBq/kg of 18F-FDG was then administrated intravenously via a T tube. After about 60 minutes of relaxed rest in a supine position in dark rooms without visual or acoustic stimulations, the patients were asked to void and were then placed into the PET/CT scanner for image acquisition. The image acquisition included non-enhanced CT scan and PET scan covered the range from the head to the middle thigh (6-8 bed position). CT scan was performed initially with a voltage of 140 kV, a current intensity of 160 mA, and 0.8-second tube rotation, and 5-mm section thickness. After CT scan finished, the scanner was repositioned to the landmark position and PET scan was then acquired with 4 min/bed position. Delayed scan was performed in the patients who needed to exclude the influence of the physiological uptake in the gastrointestinal tract.4. Image reconstruction and fusionPET images were reconstructed by using a standard iterative algorithm (ordered subset expectation maximization) with CT data being used for attenuation correction. The CT images were reconstructed by using a standard method.The thickness of each slice of PET and CT after reconstruction was 4.25mm. The acquired images of PET and CT were sent to the Xeleris (GE Medical Systems) workstation for image registration and fusion.5. Image analysis and Diagnostic CriteriaPET images and CT images were fused by frame to frame. And the images were analyzed by two experienced senior physicians in the filed of PET/CT diagnosis.(1) Diagnostic criteria for primary tumor in breast cancer1) Qualitative analysis①The focus uptake of breast mass higher than normal liver, soft tissue mass in the corresponding parts, and what ever finding lymph nodes and/or-distant disease was defined malignancy.②The focus uptake lower than normal liver, soft tissue mass in the corresponding parts, but finding lymph nodes and/or distant disease was defined malignancy. ③The focus uptake lower than normal liver, soft tissue mass in the corresponding parts, and did not finding lymph nodes and/or distant disease was defined benign.2) the the semi-quantiative analysisLesion with abnormal 18F-FDG uptake was identified by two experienced senior physicians of PET/CT. The maximum standardized uptake value (SUVmax) was calculated automatically by the workstation by setting the regions of interest (ROI) on the lesion.(2) Diagnostic criteria for recurrence and metastasis of postoperative breast cancer 6. ImmunohistochemistryImmunohistochemical detection using EliVisionTM two steps. ER, PR, Her-2 antibodies were purchased from Fuzhou Mai new biotechnology companies. With PBS instead of primary antibody as negative control, breast cancer specimens with known positive control, normal breast tissue as control.7. Staging criteriaAccording to AJCC cancer staging manual8. Statistical analysisStatistical Package for the Social Sciences (SPSS) 13.0 (SPSS Inc., Chicago, IL) was used for statistical analysis. SUVmax was expressed as mean±standard deviation (X±S). The different diagnostic efficacy of the qualitative analysis and the semi-quantiative analysis were compared and tested by McNemar's test. The agreement between different diagnostic methods was assessed with the weightedκstatistic for establishing their reliability in our study. The degrees of agreement were categorized as follows:κvalues between 0.00 to 0.40 was considered to be a poor agreement,κvalues between 0.41 to 0.70 to be a moderate agreement andκvalues between 0.71 to 1.00 to be a good agreement. Regression analysis was performed to determine the relationship between the SUV and the maximum diameter of tumor and the age of patients. Pearsonχ2 tests were performed on the cross-tables of different receptors to test any association among ER, PR and Her-2 states. Factorial ANOVA were performed to compared SUVmax measurement for different receptor states. P<0.05 was considered statistically significant.[Results]1. Diagnosis of breast cancer1.1 Breast mass group1.1.1 The diagnosis of primary tumor(1) Qualitative analysis①Based on patientsIt was detected 81 breast mass on 66 patients. If based on patients,40 breast lesions were were equal to or higher than liver uptake.1 were lower than liver uptake, but with lymph node metastasis.25 breast lesions were lower than liver uptake, and no lymph node metastasis and no distant metastasis. In the total of 66 patients enrolled,34 were ture positive lesions,7 were false positive,23 were ture negative and 2 were false negative by histopathology and multi-modalities of imaging follow- up. By the patient based, using the qualitative analysis the diagnostic sensitivity, specificity, accuracy, positive predictive and negative predictive of 18F-FDG PET/CT were 94.4%,76.7%,86.4%,82.9% and 92.0%, respectively.②Based on lesionsIt was detected 81 breast mass on 66 patients.51 were equal to or higher than liver uptake.3 were lower than liver uptake, but with lymph node metastasis or distant metastasis.27 breast lesions were lower than liver uptake, and no lymph node metastasis and no distant metastasis. In the total of 81 lesions enrolled,44 were ture positive lesions,10 were false positive,25 were ture negative and 2 were false negative by histopathology and multi-modalities of imaging follow- up. By the lesion based, using the qualitative analysis the diagnostic sensitivity, specificity, accuracy, positive predictive and negative predictive of 18F-FDG PET/CT were 95.7%,71.4%,85.2%,81.5% and 92.6%, respectively.(2) The semi-quantiative analysis①Based on patientsIn the total of 66 patients enrolled,36 of them were proven to be malignant by the histopathology examination. and 30 were proven to be benign lesions. SUVmax of breast mass in malignant group were 10.39±6.00, significantly higher than benign group 2.32±1.37 (t=7.834, P=0.000).Semi-quantitative analysis was done by determining the the Cut-off point of SUVmax using the ROC curve method. According to the ROC curve, when SUVmax≥3.3 5was set as the cut-off point for diagnosing breast cancer, youden indes was the largest and Area under the curve were 0.959, SE=0.021, (P=0.000), asymptotic 95% confidence interval were 0.918～0.999. Therefore, in the total of 66 patients enrolled,33 were ture positive lesions,5 were false positive,25 were ture negative and 3 were false negative. By the patient based, using the semi-quantitative analysis, the diagnostic sensitivity, specificity, accuracy, positive predictive and negative predictive of 18F-FDG PET/CT were 91.7%,80.0%,83.3%,87.9%,86.8% and 89.3%, respectively.②Based on lesionsIn the total of 81 breast mass enrolled,46 of them were proven to be malignant by the histopathology examination. and 35 were proven to be benign lesions. SUVmax of breast mass in malignant group were 9.600±5.848, significantly higher than benign group 2.400±1437 (t=7.992, P=0.000).Semi-quantitative analysis was done by determining the the Cut-off point of SUVmax using the ROC curve method. According to the ROC curve, when SUVmax≥3.3 was set as the cut-off point for diagnosing breast cancer, youden indes was the largest and Area under the curve were 0.917, SE=0.032, (P=0.000), asymptotic 95% confidence interval were 0.854～0.979. Therefore, in the total of 81 lesions enrolled,41 were ture positive lesions,7 were false positive,28 were ture negative and 5 were false negative. By the lesion based, using the semi-quantitative analysis, the diagnostic sensitivity, specificity, accuracy, positive predictive and negative predictive of 18F-FDG PET/CT were 89.1%,80.0%,85.2%,85.4% and 84.8%, respectively.(3) Comparison of qualitative analysis and semi-quantitative analysisBy the patient based, the agreement between the qualitative analysis and the histopathology examination was good (κ=0.721), And the semi-quantiative analysis and the histopathology examination was good too (κ=0.754). McNemar test show that the sensitivity, specificity of qualitative analysis did not differ significantly from that of the semi-quantitative analysis(94.4% vs.91.7%, P= 1.000; 76.7% vs. 86.4%, P=0.005).By the lesion based, the agreement between the qualitative analysis and the histopathology examination was moderate (κ=0.690). And the semi-quantiative analysis and the histopathology examination was moderate too (κ=0.696). McNemar test show that the sensitivity, specificity of qualitative analysis did not differ significantly from that of the semi-quantitative analysis(95.7% vs.89.1%, P=0.250; 71.47% vs.80.0%, P=0.250).(4) Correlation annlysis SUVmax and factorsIn the total of 66 patients enrolled,36 of them were proven to be malignant, and 30 were proven to be benign lesions. The age of breast mass in malignant group were 53.03±14.26, significantly higher than benign group 42.60±5.78 (t=4.011, P=0.000). The maximum diameter of breast mass in malignant group were 3.822±3.465, significantly higher than benign group 1.910±1.707 (t=2.914,P=0.005). Regression annlysis showed that the size of breast mass significantly correlated with the SUVmax (r=0.999,P=0.000). However there was no significant different between age and SUVmax (P=0.613).(5)The relationship between the state of ER, PR and Her-2 and SUVmax36 patients with breast cancer,16 (17 lesions,1 case of bilateral breast cancer) of them were examined by immunohistochemistry.Pearsonχ2 test were performed on the cross-tables of different receptor to test for any association among ER, PR and Her-2. Between ER and PR states, it was found that if one is positive the other tends to be positive as well (γ=0.964, P=0.000). However, no correlation was detected between ER and Her-2 (P=0.313) or PR and Her-2 (P=0.313).Only considered the main effect of three factors, ANOVA show that the SUVmax of the Her-2+ lesions and the SUVmax of the Her-2- lesions were significantly different (F=5.835, P=0.034), However, no significantly differences were found between the SUVmax of the ER+ and ER- lesions (F=0.025, P=0.877) or the PR+ and PR-lesions (F=0.410, P=0.535). ER and PR states had no effect on 18F-FDG uptake, but the Her-2 state alone had an effect on F-FDG uptake.ER excluded, ANOVA show that the SUVmax of PR+ and Her-2+ lesions were significantly different from the SUVmax of PR- and Her-2-lesions (F=5.966, P=0.030; F=7.863, P=0.015). But no interaction was detected between ER and PR states(F=2.437, P=0.143).1.1.2 Lymph node metastasis36 patients with breast cancer,21 patients with lymph node metastasis: Ipsilateral axillary lymph node metastasis in 6 patients (N1+N2); ipsilateral axillary lymph node metastasis and ipsilateral parasternal (internal mammary) lymph node metastasis in 4 patients, ipsilateral supraclavicular fossa lymph node metastasis in 1 patient, and ipsilateral subclavian lymph node metastasis in 1 patients (N3); Distant lymph node metastasis in 9 patients, including the bilateral axillary, mediastinum, the hilar and retroperitoneal lymph nodes metastasis. The smallest diameter of lymph node metastasis detected by 18F-FDG PET/CT was 0.5.1.1.3 Distant metastasis36 patients with breast cancer,8 patients with distant metastasis. It were detected 11 metastasis, including 4 (11.1%) liver metastasis,4 (11.1%) bone metastasis,1 (2.8%) lung metastasis,1 (2.8%) pancreas metastasis and 1 (2.8%) adrenal metastasis.2. The role of 18F-FDG PET/CT in detection of recurrent, metastasis and restaging on postoperative breast cancer2.1 The role of 18F-FDG PET/CT in detection of recurrent on postoperative breast cancer2.1.1 Based on patientsOf 104 postoperative breast cancer,8 paitients recurrent. By the patient based, The sensitivity, specificity, accuracy positive predictive and negative predictive of PET/CT in detecting recurrent tumor were 100.0%,100.0%,100.0%,100.0%and 100.0% respectively.2.1.2 Based on lesionsOf 104 postoperative breast cancer,8 lesion recurrent. By the lesions based, the sensitivity, specificity, accuracy positive predictive and negative predictive of PET/CT in detecting recurrent tumor were 100.0%,100.0%,100.0%,100.0%and 100.0%, respectively.2.2 The role of 18F-FDG PET/CT in detection of metastasis on postoperative breast cancer2.2.1 Based on patientsBy the patient based, the diagnosis of metastasis on 104 postoperative breast cancer by 18F-FDG PET/CT show that there were 51 ture positive lesions,1 false positive,52 ture negative and no false negative. The sensitivity, specificity, accuracy positive predictive and negative predictive of PET/CT in detecting recurrent tumor and/or metastasis were 100.0%,98.1%,99%,98.1% and 100.0%,respectively.2.2.2 Based on lesions119 positive lesions were detected on 104 postoperative breast cancer by 18F-FDG PET/CT, and there were 8 lesions on the residual or chest,48 lymph node metastasis including 10 ipsilateral axillary,18 ipsilateral supraclavicular or subclavian fossa,12 hilar or mediastinal,3 parasternal,2 contralateral axillary or contralateral subclavian fossa,1 retroperitoneal area and 1 pelvic area lymph node metastasis, and 63 organ metastasis including 17 lung,15 liver,22 bone,5 pleeral,4 brain,2 contralateral breast,1 colon and 1 bone marrow cavity metastasis.2 positive lesion were proven to be inflammatory by pathology.8 negative lesions were detected on 104 postoperative breast cancer by 18F-FDG PET/CT, including 3 chest, 2 liver and 3 bone lesions.2 bone lesions were proven to be false negative lesions. They were detected by SPECT. By the lesions based, the sensitivity, specificity, accuracy positive predictive and negative predictive of PET/CT in detecting metastasis were 98.2%,75.0%,96.8%,98.3%and 75.0%,respectively.2.3 The role of 18F-FDG PET/CT restaging on postoperative breast cancerOf 104 postoperative breast cancer,51 patients had recurrence or metastasis. There were 3 patients in stageⅡ,10 patients in stageⅢand 38 patients in stageⅣby clinical examinnation. Howerer, there were 1 patients in stage 0,8 patients in stageⅢand 43 patients in stageⅣby PET/CT.18F-FDG PET/CT upstaged 6 cases because of lymph node metastasis or distant metastasis:1 case in stage II raised to stageⅢ,2 case in stageⅡraised to stage IV and 3 case in stageⅢraised to stage IV. 1 case downstage because of no node metastasis.5 cases changed the treatment including 1 case changed the chemotherapy regimen,4 cases changed to systemic chemotherapy and radiotherapy which were follow-up.1 case which did no change the clinical stage changed chemotherapy because of appearancing new lesions repeatly.[Conclusions]1. 18F-FDG PET/CT imaging in the diagnosis of breast mass, has important value and can effectively distinguish between malignant and benign lesions. Qualitative analysis, quantitative analysis and CT can complement and reflect each other, and has goog for diagnosising breast cancer.2. Primary breast cancer and metastasis have similar biological behavior, and have similar 18F-FDG uptake. Because of whole body imaging, PET/CT has obvious advantages on the evaluation of the whole body of breast canncer.3. The size of breast mass significantly correlated with the SUVmax, small lesions usually underestimated SUVmax.4. The relationship between the state of ER, PR and Her-2 and SUVmax: Between ER and PR states, it was found that if one is positive the other tends to be positive as well. However, no correlation was detected between ER and Her-2 or PR and Her-2. The SUVmax of the Her-2+ lesions and the SUVmax of the Her-2-lesions were significantly different. However, no significantly differences were found between the SUVmax of the ER+ and ER- lesions or the PR+ and PR- lesions. ER excluded, the SUVmax of PR+ lesions were significantly different from the SUVmax of PR- 5. 18F-FDG PET/CT in detection of recurrent and(or) metastasis and restage on postoperative breast cancer has important clinical value.6. Part of intraductal papilloma, breast fibroadenoma and accute inflammation is usually be misdiagnosed, and the early breast cancer with smaller lesions would be ignored in PET/CT scans because of low 18F-FDG uptake, so it is key to analyze the synthetic examinations for diagnosing. |
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