Patients
Patient characteristics are summarized in . The median follow-up time for the 225 patients in the study after initial diagnosis of breast cancer was 26.7 months (range, 1–68 months). The reasons for performing PET/CT were equivocal or suspicious findings on conventional imaging (116 patients), locally advanced breast cancer (98 patients), to rule out primary cancer (seven patients), unknown (two patients), and patient request (two patients).
Distant Metastasis Rate and Patient Outcomes as per Distant Metastasis
The numbers of patients with and without distant metastases, as well as the outcomes of patients in these two groups, are summarized in . Seventy-eight patients were judged to have distant metastases on the basis of histological confirmation (27 patients), subsequent imaging (30 patients), or clinical follow-up (21 patients). One hundred forty-seven patients were judged not to have distant metastases. Of these, 56 patients were initially suspected of having metastases on the basis of PET/CT alone (eight patients), conventional imaging (43 patients), or both PET/CT and conventional imaging (five patients), but were judged not to have distant metastases on the basis of histological confirmation (10 patients), subsequent imaging (28 patients), or clinical follow-up (18 patients). The median follow-up time for the 18 patients with distant metastases ruled out on the basis of clinical follow-up was 42 months (range, 24–68 months).
Of the 147 patients judged not to have distant metastases, no patients died during follow-up, 20 patients relapsed, and 127 patients remained progression free. The sites of relapse in the 20 patients with relapse were local lymph node (n = 4), distant lymph node (n = 3), bone (n = 4), brain (n = 4), lung (n = 4), and liver (n = 4) (some patients had relapse at more than one site).
Conventional Imaging
Findings on conventional imaging are summarized in .
| Table 2.Conventional imaging rates and findings |
The utility of conventional imaging in the detection of distant metastases from breast cancer is outlined in . On conventional imaging, 115 patients (51%) had suspected distant metastases, and 67 (58%) of these 115 patients were judged positive for distant metastases. The sensitivity of conventional imaging in the detection of distant metastases was 85.9% and the specificity was 67.3% ().
| Table 3.Sensitivity and specificity of PET/CT and conventional imaging |
PET/CT
On PET/CT, 136 patients were not suspected of having distant metastases. Two of those patients actually had distant metastases as indicated by biopsy (one of two) or subsequent imaging (one of two). The sensitivity of PET/CT in the detection of distant metastases was 97.4% (). One of the two patients with false-negative PET/CT findings had a bone metastasis that was suggested by bone scan and confirmed by MRI. That patient had no disease progression over a follow-up time of 26 months. The other patient with false-negative PET/CT findings had mediastinal pleural metastasis suggested by CT of the chest and confirmed by cytology. That patient experienced progression of disease after 11 months.
On PET/CT, 89 patients had suspected distant metastases. Thirteen of these 89 patients did not actually have distant metastases as indicated by biopsy (one of 13), additional imaging (four of 13), or clinical follow-up (eight of 13). The specificity of PET/CT in the detection of distant metastases was 91.2% ().
In the 13 patients with false-positive PET/CT findings, the sites of false-positive findings on PET/CT were bone (n = 7), ovary (n = 3), lung (n = 2), mediastinal lymph node (n = 1), and liver (n = 1), with some patients having multiple false-positive sites. None of the 13 patients with false-positive PET/CT findings had a recurrence, and all were alive at a median follow-up time of 23.2 months. In seven of the 13 patients with false-positive PET/CT findings, systemic therapy was given as though there was stage IV disease.
Sensitivity and Specificity of PET/CT and Conventional Imaging
The sensitivity of PET/CT (97.4%) was significantly higher than the sensitivity of conventional imaging (85.9%) (p = .009). The specificity of PET/CT (91.2%) was significantly higher than the specificity of conventional imaging (67.3%) (p < .001).
We also analyzed sensitivity and specificity in three different subgroups of patients in our series. First, we excluded the 25 patients with stage IV disease at presentation prior to primary staging. In the remaining 200 patients, the sensitivity and specificity of PET/CT were 96% and 91%, respectively, and those of conventional imaging were 84% and 67%, respectively. There was a significant difference in accuracy between PET/CT and conventional imaging (p < .001) (supplemental online Table S1). Second, we limited the analysis to patients without stage IV disease at presentation who had locally advanced breast cancer (n = 134). In this group, the sensitivity and specificity of PET/CT were 98% and 90%, respectively, and those of conventional imaging were 83% and 85%, respectively (supplemental online Table S2). Again, there was a significant difference in accuracy between PET/CT and conventional imaging (p = .0411). Third, we limited the analysis to patients without stage IV disease at presentation who had early breast cancer (n = 66). In this group, the sensitivity and specificity of PET/CT were 91% and 93%, respectively, and those of conventional imaging were 91% and 38%, respectively (supplemental online Table S3). There was again a significant difference in accuracy between the two diagnosis methods (p < .001).
Cases Detected by FDG-PET/CT and Not by Conventional Imaging
In 15 patients, PET/CT findings suggested distant metastases that were not suspected on the basis of conventional imaging findings, and these PET/CT findings prompted administration of systemic therapy for presumed stage IV disease. In other words, in 15 patients, the results of PET/CT changed the clinical management. In 11 of those patients, distant metastases were confirmed by subsequent biopsy or conventional imaging studies (). However, in the other four patients, distant metastases were not confirmed by subsequent biopsy or imaging. The follow-up durations in these four patients were 12 months, 24 months, 26 months, and 25 months.
| Table 4.Cases with distant metastases detected by PET/CT but not detected on conventional imaging |
Performance of PET/CT and Conventional Imaging by Disease Site
shows the performance of PET/CT compared with conventional imaging in the detection of metastases in bone, in lymph nodes in the chest, in the lungs, and in the liver.
| Table 5.Comparison of PET/CT and conventional imaging at individual sites of metastasis |
Fifty-six patients in our study had bone metastases. PET/CT detected bone metastases in 55 of those patients, failed to detect bone metastases in one of those patients, and incorrectly suggested bone metastases in seven patients. SS detected bone metastases in 38 patients, failed to detect bone metastases in 12 patients (six patients did not undergo SS), and incorrectly suggested bone metastases in 21 patients. The sensitivity and specificity of PET/CT for detecting bone metastases were 98% and 96%, respectively, compared with 76% and 86%, respectively, for SS.
Twenty-five patients in our study had metastases in the lymph nodes of the chest, and 14 patients had lung metastases. The only chest or lung metastasis not detected by PET/CT and detected by chest CT was a lesion of the mediastinal pleura. PET/CT detected two mediastinal nodal metastases and one hilar nodal metastasis not detected by chest CT.
Twenty patients in our study had liver metastases. Both PET/CT and abdominal CT accurately detected liver metastases in all cases. PET/CT incorrectly indicated liver metastases in one patient, and abdominal CT incorrectly indicated liver metastases in nine patients. In the detection of liver metastases, the sensitivity and specificity of PET/CT were 100% and 99%, respectively, compared with 100% and 95%, respectively, for CT.