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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 10  |  Page : 661-666

2-fluoro-2-deoxy-D-glucose positron emission tomography versus conventional imaging for the diagnosis of breast cancer and lymph node metastases


1 Department of Surgery, Linyi People's Hospital, Linyi 276003, Shandong Province, China
2 Department of Nuclear Medicine, Jinhua Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua 321000, Zhejiang, China

Date of Web Publication24-Sep-2018

Correspondence Address:
Guanghua Wen
Department of Nuclear Medicine, Jinhua Central Hospital, Jinhua Hospital of Zhejiang University, Mingyue Road 351, Jinhua 321000, Zhejiang
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.207069

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 > Abstract 


Context: Proper preoperative staging is vital in the treatment of breast cancer patients. Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) and conventional diagnostic modalities including ultrasonography (US), mammography (MG), and magnetic resonance imaging (MRI) play a greater role.
Aims: To evaluate the diagnostic accuracy of FDG-PET in detecting primary breast cancer as compared with US, MG, and MRI, and in axillary lymph nodes (ALNs) staging in Chinese women.
Settings and Design: It is a study of diagnostic accuracy.
Subjects and Methods: Thirty-one female patients, with biopsy established breast carcinoma, were recruited and analyzed retrospectively. All patients underwent 18F-FDG-PET, MG, US, and MRI. FDG-PET/CT for the diagnosis of primary breast cancer and detecting ALNs metastases were compared with MG, US, and MRI.
Statistical Analysis Used: Sensitivity, specificity, positive-predictive value (PPV), and negative-predictive value (NPV) of FDG-PET imaging for primary breast cancers and ALN staging were analyzed using standard statistical analyses.
Results: In 31 patients with cytologically established invasive breast carcinoma, the sensitivities of US, MG, MRI, and FDG-PET/CT were 90% (28/31), 84% (26/31), 97% (30/31), and 94% (29/31), respectively. The sensitivity, specificity, overall accuracy, PPV, and NPV of US, MRI, and FDG-PET/CT in ALN staging (maximum standardized uptake value cutoff at 1.5) were 80%, 86%, 84%, 80%, and 90%; 90%, 95%, 94%, 90%, and 95%; and 90%, 86%, 87%, 90%, and 95%, respectively.
Conclusions: US and MRI should remain the first line for the diagnosis of breast cancer. Both MRI and FDG-PET/CT could accurately diagnose the primary breast cancer and stage the axilla lymph nodes, but further large population study is needed.

Keywords: 2-fluoro-2-deoxy-D-glucose positron emission tomography, breast cancer, magnetic resonance imaging, mammography, ultrasonography


How to cite this article:
Shao M, Zi J, Wen G. 2-fluoro-2-deoxy-D-glucose positron emission tomography versus conventional imaging for the diagnosis of breast cancer and lymph node metastases. J Can Res Ther 2018;14, Suppl S3:661-6

How to cite this URL:
Shao M, Zi J, Wen G. 2-fluoro-2-deoxy-D-glucose positron emission tomography versus conventional imaging for the diagnosis of breast cancer and lymph node metastases. J Can Res Ther [serial online] 2018 [cited 2020 Oct 24];14:661-6. Available from: https://www.cancerjournal.net/text.asp?2018/14/10/661/207069




 > Introduction Top


Proper preoperative staging is vital in the treatment of breast cancer patients. Conventional diagnostic modalities including ultrasonography (US), mammography (MG), and magnetic resonance imaging (MRI) are used in the initial diagnosis of breast cancer and axillary lymph nodes (ALNs) involvement. Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) had the advantages of allowing chest, abdomen, and bone to be examined in a single session[1] which has been expected to evaluate patients with breast cancer and ALN involvement with a sensitivity from 20% to 96%.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11] In this study, we retrospectively compared the diagnostic efficacy of FDG-PET/CT with US, MG, and MRI in detecting primary breast cancer and lymph node metastases.


 > Subjects and Methods Top


Ethics

The study was carried out with Hospital Ethics Committee Approval and oral informed consent from each patient with regard to 18F-FDG-PET/computed tomography (CT) and the entry into the present study.

Study design

Selection and description of participants

Thirty-one patients with cytologically established breast carcinoma were retrospectively enrolled in the study. It is a study of diagnostic accuracy. The median age of the patients was 45 years (23–70 years). All patients underwent preoperative FDG-PET/CT, US, MG, and MRI.

Conventional imaging techniques

Ultrasonography

An expert radiologist performed bilateral US of the breast and axilla with a high-frequency linear array transducer (L8-14 MHz) on a Siemens Acuson Sequoia 512 (USA). The solid lesions of the shape, boundary, echogenicity, calcification, enhancing or decreasing of postlesion and color Doppler signal in breast were observed. The location, size, shape, internal echo, lymph hilum, corticomedullary structure, and flow pattern of lymph node were explored. Lymph nodes were categorized as suspicious if they exhibited one or more of the following characteristics: overall enlargement, cortical thickening, or eccentric cortical lobulation with obliteration of echogenic hilum, irregular shape, loss of fatty hilum, or round shape.[12]

Magnetic resonance imaging

MRI was performed with two different scanners: a 1.5-T dedicated spiral breast MRI system with a single-channel quadrature breast coil (Aurora Systems, USA) and a 3.0-T whole-body MRI scanner with an eight-channel phase-array breast coil (Signa HDxt, GE Medical System). All patients were placed in the prone position, feet first, on the table inside the MRI scanner. For the dynamic imaging, the gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA; Magnevist; Bayer Schering Pharma AG, Berlin, Germany) was intravenously administered at a dose of 0.2 mmol/kg of body weight as a bolus at a flow rate of 2 mL/s followed by a 20-mL normal-saline flush. Dynamic imaging of both breasts was obtained before and at 180 s, 360 s, and 540 s after the injection of Gd-DTPA.[13]

Mammography

Mediolateral oblique and craniocaudal digital MG of the breast were performed using a molybdenum-rhodium target full-field digital MG system (Senographe 2000D, General Electric, Pittsburgh, PA, USA). If required, additional MG views were obtained. The imaging interpretation was based on the American College of Radiology Breast Imaging Reporting and Data System lexicon.[14]

Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography imaging techniques

A PET/CT scan was carried out 3–7 days before surgery. The patients were fast for a minimum of 6 h before injection. Blood glucose level was measured in each patient to verify that blood glucose was <11 mmol/L. Intravenous administration of 5.3 MBq/kg ± 10% of 18F-FDG was administered in the forearm opposite the primary breast tumor. After injection, patients stayed in the PET preparation room and rested for 1 h. Just before the end of the 1 h uptake period, the patients emptied their urine bladder.

Image acquisition was performed using an integrated PET/CT system (Biograph, Siemens, Germany). Images were obtained 1 h after injection from head basis to mid-thigh; 5–7-bed positions were acquired, for a total of 5,000,000 counts. Standard protocol: emission time/bed position, 3 min; attenuation correction, 137Cs; rotations/bed position. Attenuation-corrected images were reconstructed in transaxial, coronal, and sagittal planes. CT scan was performed with a four-slice multidetector helical scanner. The emission images were reconstructed with the ordered subset expectation maximization implementation of iterative reconstruction (two iterations, 28 subsets). Attenuation-corrected emission data were obtained using the CT reconstructed with filtered back projection, a bilinear fit of attenuation coefficients, and a Gaussian filter with 8 mm full width at half maximum to match the PET resolution.

The 18F-FDG-PET/CT images were reviewed by two experienced nuclear medicine physicians, and images were considered positive if there was focal uptake in breast and axillary basin. To establish the maximum standardized uptake value (SUVmax) cutoff points and PET diagnostic accuracy in determining ALN involvement, SUVs ranging from 1 to 2.5 were set. The cutoff point or greater was defined as positive, and SUV less than the point was defined as negative. Based on each SUVmax cutoff point, the diagnostic accuracy of 18F-FDG-PET (positive or negative) was evaluated by means of sensitivity, specificity, positive-predictive value (PPV), and negative-predictive value (NPV). The interpreting physicians were blinded to any pathological assessment of primary breast tumor and ALN.

Surgery and pathologic review

The protocol for pathology review was developed by the pathology review committee. The size of breast tumor was measured, and tumors were classified according to the American Joint Committee on Cancer (Edition 5) staging criteria: T1a–b (≤10 mm), T1c (11–20 mm), T2 (21–50 mm), or T3 (>50 mm). The number, maximum size, and nuclear grade of involved primary breast cancer and ALNs were also histopathologically examined. Pathologists were blinded to FDG-PET interpretations.

Statistical analysis

The SUVmax cutoff values for the semiquantitative assessment of 18F-FDG-PET/CT were set at 2.5, 2, 1.5, and 1. The sensitivity, specificity, PPV, and NPV of FDG-PET imaging for primary breast cancers and ALN staging were analyzed using standard statistical analyses. The diagnostic performances of FDG-PET/CT in detecting primary breast tumor and lymph node metastases, MG, US, and MRI were analyzed based on the calculation of sensitivity (true positive [TP]/[TP + false negative (FN)]), specificity (true negative [TN]/[TN + false positive (FP)]), PPV (TP/[TP + FP]), and NPV (TN/[TN + FN]). The overall accuracy was calculated as the percentage of all TP and TN cases out of the total number of cases.


 > Results Top


Patient characteristics

The characteristics of 31 patients including age, pathological factor, histological type, nuclear grade, hormone receptor status, and human epidermal growth factor receptor 2 status of the primary tumors, median SUVmax of the primary tumors, and axillary uptake are listed in [Table 1]. Two patients (6.5%) had pT1mic/1a of breast cancer, 28 (90.3%) cases at pT1-2, and 1 (3.2%) case at pT3. Nineteen (61.3%) patients had no lymph node metastases of breast cancer while 12 (38.7%) cases had lymph node metastases. Twenty-one (68%) patients had menopause. Two patients had multifocal lesions in a breast which were showed by PET/CT and conventional imaging [Figure 1].
Table 1: Thirty-one patients' characteristics

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Figure 1: (a) A 58-year-old female patient had invasive lobular carcinoma in the left breast. Axial fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography showed two nodules in the left breast with maximum standardized uptake value 4.99. (b) Diffusion-weighted imaging magnetic resonance imaging showed two masses with irregular margin and a heterogeneous signal at left upper outer breast. (c) Ultrasound revealed two low echo areas at the left breast. (d) Mammography also displayed two focal nodules with high density at left upper outer breast (Breast Imaging Reporting and Data System 4C) (d)

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2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography for the diagnosis of primary breast cancer compared with ultrasonography, mammography, and magnetic resonance imaging

In 31 patients with cytologically established breast carcinoma, the sensitivities of US, MG, MRI, and FDG-PET/CT were 90% (28/31), 84% (26/31), 97% (30/31), and 94% (29/31), respectively [Table 2].
Table 2: 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography and conventional imaging modalities in detection of primary breast carcinomas

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2-fluoro-2-deoxy-D-glucose positron emission tomography for axillary lymph node staging and maximum standardized uptake value cutoff points

The sensitivity, specificity, overall accuracy, PPV, and NPV of US, MRI, and FDG-PET/CT in ALN staging (SUVmax cutoff at 1.5) were 80%, 86%, 84%, 80%, and 90%; 90%, 95%, 94%, 90%, and 95%; and 90%, 86%, 87%, 90%, and 95%, respectively. The FP and FN rates were 27% (3/11) and 10% (2/20) by US; 9% (1/11) and 5% (1/21) by MRI; and 25% (3/12) and 5% (1/19) by FDG-PET/CT, respectively [Table 3].
Table 3: Axillary node staging by ultrasonography, magnetic resonance imaging, and 2-fluoro-2-deoxy-D-glucose positron emission tomography

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The diagnostic accuracy of FDG-PET was evaluated using various SUVmax cutoff points ranging from 1 to 2.5. As SUVmax increased from 1 to 1.5, specificity increased from 79% to 94% and sensitivity decreased from 39% to 35%. As SUVmax increased from 1 to 2.5, specificity increased from 79% to 99%, but sensitivity decreased from 39% to 11%. Therefore, the SUVmax of 1.5 achieved better specificity and PPV [Table 4].
Table 4: Maximum standardized uptake value cutoff points in the diagnostic performance of 2-fluoro-2-deoxy-D-glucose positron emission tomography computed tomography in axillary lymph nodes staging

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 > Discussion Top


Preoperative US, MG, contrast-enhanced breast and axilla magnetic resonance imaging (cMRI) and 18F-FDG-PET/CT are noninvasive methods that are usually conducted for the evaluation of patients with breast cancer.[15] 18F-FDG-PET/CT protocol had similar accuracy to MRI for the detection of breast cancer lesions. FDG-PET/CT has been expected to evaluate patients with suspicious of breast cancer with a sensitivity varying from 63% to 93% in detecting primary breast cancer, of 63%,[3],[11] 76.2%,[16] 93%[17] and 96% (24/24),[18] 94% obtained in our study. It is of note that the studies were also conducted in a relatively small patient group, varying from 15 to 86. Moreover, we included patients with cytologically established breast cancer while patients with suspicious of tumor were included in other studies. MG (84%) had a slight lower sensitivity than US (90%), MRI (97%), and FDG-PET/CT (94%) in our study. Corresponding to our study, the sensitivity of US (95.9%) was better than MG (88.5%) in the preoperative evaluation of breast diseases of Chinese women.[19] In nonfatty breasts, US and MR imaging were more sensitive than MG for invasive cancer, but both MR imaging and US involved risk of overestimation of tumor extent.[20] The diagnostic accuracy of MRI in our small sample showed a high sensitivity (97%), which is in concordance with that by Rieber et al. (100%)[17] and Heinisch et al. (95.2%).[16] Therefore, the initial assessment of the 18F-FDG-PET/CT protocol indicates similar accuracy to MRI for the detection of breast cancer lesions.[21]

Noninvasive evaluation of multifocality is challenging. Invasive lobular carcinoma (ILC) is more often multifocal and multicentric[22] as well as bilateral than invasive ductal carcinoma (IDC).[23] In the current study, cMRI, US, MG, and FDG-PET/CT are all helpful for the evaluation of the multiplicity in the breast for two patients.[24] cMRI has been shown to be more accurate in terms of preoperative staging and determining the extent of ILC than MG or US. A recent study found that the detection rates of MRI and 18F-FDG-PET/CT for the primary cancer do not differ between the ILC and IDC groups.[25],[26] Choi et al.[27] reported that the sensitivity of 18F-FDG-PET/CT for multiple additional lesions was lower than that of both MRI and US (12.5%, 80%, and 78.4%, respectively); however, the specificity was highest among the three modalities (99.1%, 92.1%, and 86.3%, respectively). The authors reported that they did not find a diagnostic role of 18F-FDG-PET/CT in differentiating multiple tumors from a single tumor, with its low sensitivity of 12.5%. Computer-aided detection MRI is feasible to assess multifocality in invasive breast cancer patients.[28] Both MG and US tend to underestimate lesion size and miss multifocal or multicentric lesions.[24],[29] The high sensitivity of MRI for multiple additional lesions of ILC has been reported previously.[25],[29],[30]

In the assessment of ALNs, controversial results have been reported.[31],[32] PET/CT has higher sensitivity, NPV, and accuracy values than cMRI and may guide a surgical decision to proceed or not to sentinel lymph node biopsy or ALN dissection.[31] PET/CT is able to assess axillary lymphatic status more accurately than traditional diagnostic methods and change the treatment plan established upon the results of traditional imaging modalities in 18 patients (15.6%).[33] Contrarily, both PET/CT and US have poor sensitivity and cannot replace staging by using the sentinel node procedure.[32] In our study, FDG-PET/CT indicated similar accuracy to MRI for the detection of axillary nodes metastasis with a sensitivity of 90% while 80% for US. Both MRI and FDG-PET/CT are relatively accurate methods for the evaluation of ALN metastasis as well.[24],[34],[35]

The main limitation of the current study was the small number of cases. Second, the study is retrospective. Third, a number of patients had a low-risk breast cancer (patients, pT1a/b/c in >75% of patients; N0/1 in >80% of patients) in the study which may have a selection bias.


 > Conclusion Top


US and MRI should remain the first line for the diagnosis of breast cancer. Both MRI and FDG-PET/CT could accurately diagnose the primary breast cancer and stage the axilla lymph nodes, but further large population study is needed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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