1 Introduction

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is currently used in daily clinical practice for the evaluation of breast cancer (BC) patients. This chapter provides an overview of the current evidence-based data on the usefulness of PET/CT (using 18F-FDG and other radiotracers) for different indications in patients with BC.

2 Staging

A recent network meta-analysis comparing 19 different imaging methods demonstrated the relatively higher specificity of 18F-FDG PET/CT compared to other imaging methods for the detection of BC lesions [1].

Liang et al. [2] evaluated through a meta-analytic approach the accuracy of magnetic resonance imaging (MRI) and 18F-FDG PET/CT for lymph nodal (N) staging of early BC. The pooled specificities of MRI and PET/CT for diagnosing regional lymph nodal status in BC patients were similar (93%); however, the pooled sensitivity of MRI was significantly greater than PET/CT (82% versus 64%), respectively.

Hong et al. [3] performed a meta-analysis to evaluate the value of 18F-FDG PET/CT for diagnosis of distant metastases of BC. Pooled sensitivity and specificity of 18F-FDG PET/CT were 96% (95%CI: 90–98%) and 95% (95%CI: 92–97%), respectively. Compared with conventional imaging, 18F-FDG PET/CT has higher sensitivity for diagnosis of distant metastases in BC patients.

Similar findings were reported in another meta-analysis by Sun et al. [4]: pooled sensitivity and specificity of 18F-FDG PET or PET/CT were 99% (95%CI: 88–100%) and 95% (95%CI: 89–98%), respectively, confirming the excellent diagnostic performance of 18F-FDG PET/CT for distant metastasis staging in BC patients compared to conventional imaging.

Rong et al. [5] found that the pooled sensitivity and specificity of 18F-FDG PET/CT for detecting bone metastases of BC were 93% (95%CI: 82–98%) and 99% (95%CI: 95–100%), respectively. Compared with bone scintigraphy, 18F-FDG PET/CT has higher sensitivity and accuracy for detection of bone metastases in BC patients.

3 Restaging and Assessment of Response to Neoadjuvant Therapy

Evangelista et al. [6] performed a meta-analysis on the use of tumour markers in BC patients as a guide for 18F-FDG PET imaging. The meta-analysis provided the following results: pooled sensitivity 87.8% (95%CI: 83.8–90.9%) and pooled specificity 69.3% (95%CI: 55.3–80.5%), confirming the role of 18F-FDG PET/CT in detecting metastases in the presence of a progressive increase of serum tumour markers in BC patients.

Xiao et al. [7] found that the pooled sensitivity and specificity of 18F-FDG PET or PET/CT in detecting BC recurrence were 90% (95%CI: 88–90%) and 81% (95%CI: 78–84), respectively. Therefore, 18F-FDG PET/CT is a valuable imaging method to detect relapse in suspected recurrent BC patients.

Several meta-analyses evaluated the usefulness of 18F-FDG PET/CT in predicting the response to neoadjuvant therapy in BC patients. According to Wang et al. [8], the pooled sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT in this setting were 84% (95%CI: 78–88%), 66% (95%CI: 62–70%), 50% (95%CI: 44–55%) and 91% (95%CI: 87–94%), respectively. For regional lymph nodes, sensitivity and NPV of 18F-FDG PET/CT were 92% (95%CI: 83–97%) and 88% (95%CI: 76–95%), respectively. Overall, 18F-FDG PET/CT is useful to predict neoadjuvant therapy response in BC patients, but the relatively low specificity and PPV still call for caution. Cheng et al. [9] found similar results of 18F-FDG PET/CT in this setting reporting a pooled sensitivity and specificity of 84.7% (95%CI: 79.3–89.2%) and 66.1% (95%CI: 59.8–72.0%), respectively, indicating that 18F-FDG PET/CT has reasonable sensitivity in evaluating response to neoadjuvant chemotherapy in BC, but the specificity is relatively low. Mghanga et al. [10] found that 18F-FDG PET has moderately high sensitivity (80.5%; 95%CI: 75.9–84.5%) and specificity (78.8%; 95%CI: 74.1–83.0%) in early detection of responders from nonresponders, and it can be used for the evaluation of response to neoadjuvant chemotherapy in BC patients. Another meta-analysis [11] reported that the pooled sensitivity and specificity of 18F-FDG PET/CT in this setting were 81.9% (95%CI: 76.0–86.6%) and 79.3% (95%CI: 72.1–85.1%), respectively, confirming the moderate accuracy of 18F-FDG PET/CT in predicting neoadjuvant therapy response in BC patients.

Several meta-analyses compared 18F-FDG PET/CT and MRI for evaluation of treatment response to neoadjuvant chemotherapy (NAC) in BC patients. Liu et al. [12] reported that 18F-FDG PET/CT has a higher sensitivity and MRI has a higher specificity in assessing pathological complete response (pCR) after NAC in BC patients. The pooled sensitivity and specificity of 18F-FDG PET/CT were 86% (95%CI: 76–93%) and 72% (95%CI: 49–87%), respectively. Therefore, the combined use of these two imaging modalities may have great potential to improve the diagnostic performance in assessing pCR after NAC. Another meta-analysis [13] indicates that the timing of imaging for NAC-response assessment exerts a major influence on the estimates of diagnostic accuracy: 18F-FDG PET/CT outperformed MRI in intra-NAC assessment, whereas the overall performance of MRI was higher after completion of NAC, before surgery. The pooled estimates of sensitivity and specificity were 71% and 77% for 18F-FDG PET/CT and 88% and 55% for MRI, respectively. Chen et al. [14] found that the diagnostic performance of MRI is similar to that of 18F-FDG PET/CT for the assessment of BC response to NAC. For 18F-FDG PET/CT, the pooled sensitivity was 87% (95%CI: 71–95%) and pooled specificity was 85% (95%CI: 70–93%). For MRI, the pooled sensitivity was 79% (95%CI: 68–87%) and the pooled specificity was 82% (95%CI: 72–89%). However, 18F-FDG PET/CT is more sensitive than conventional contrast-enhanced MRI and more specific if the second imaging scan is performed before three cycles of NAC. Lastly, Li et al. [15] found that MRI had a higher sensitivity and 18F-FDG PET/CT had a higher specificity in predicting the pathologic response after NAC in patients with BC, with similar accuracy among the two methods. The pooled sensitivity and specificity of MRI were 88% (95%CI: 78–94%), and 69% (95%CI: 51–83%), respectively. The corresponding values for 18F-FDG PET/CT were 77% (95%CI: 58–90%) and 78% (95%CI: 63–88%), respectively.

4 Prognostic Value

Diao et al. [16] evaluated the prognostic value of maximum standardized uptake values (SUVmax) measured in the primary lesion and axillary lymph nodes (ALN) by pretreatment 18F-FDG PET or PET/CT in patients with BC. For event-free survival (EFS), patients with higher SUVmax in primary tumour and ALN showed a poorer prognosis with pooled hazard ratio (HR) of 1.96 (95%CI: 1.40–2.73) and 1.89 (95%CI: 0.70–5.07), respectively. In analysing invasive ductal carcinoma (IDC) patients, the pooled HR was 1.91 (95%CI: 1.40–2.64). For overall survival (OS), the pooled HR of SUVmax in primary lesion and ALN were 0.64 (95%CI: 0.23–1.84) and 1.09 (95%CI 0.07–16.53), respectively. Therefore, patients with BC and higher SUVmax in primary lesion or ALN may experience a higher risk for recurrence or a poor progression.

5 Incidental 18F-FDG Uptake

A meta-analysis calculated the prevalence and clinical significance of breast incidental 18F-FDG uptake (BIU) detected by PET or PET/CT in patients performing PET for other reasons than BC evaluation [17]. The pooled prevalence of BIU on all PET scans was 0.4% (95%CI: 0.23–0.61%), the pooled prevalence on PET scans on female patients only was 0.82% (95%CI: 0.51–1.2%), the pooled risk of malignancy of BIU when further evaluated was 48% (95%CI: 38–58%) and the pooled risk of malignancy of BIU with histological examination was 60% (95%CI: 53–66%). Despite being uncommon, the identification of BIU frequently signals the presence of an unsuspected subclinical lesion and the risk of malignancy is very high.

6 18F-FDG Positron Emission Mammography

The diagnostic performance of dedicated 18F-FDG positron emission mammography (PEM) in evaluating suspicious BC has been investigated by a meta-analytic study [18]: pooled sensitivity and specificity of 18F-FDG PEM in women with suspected breast malignancy were 85% (95%CI: 83–88%) and 79% (95%CI: 74–83%), respectively, on a per-lesion-based analysis. The detection of additional breast lesions and extensive intraductal involvement is improved by PEM, with comparable accuracy over that of MRI in the depiction of invasive BC.

7 PET/MRI

Lin et al. [19] performed a meta-analysis to assess the staging/restaging performance of hybrid 18F-FDG PET/MRI in BC patients. The pooled sensitivity and specificity of 18F-FDG PET/MRI for staging/restaging BC were 98% (95%CI: 95–99%) and 87% (95%CI: 76–95%), respectively, on a per-patient analysis and 91% (95%CI: 88–94%) and 95% (95%CI: 92–97%), respectively, on a per-lesion analysis. Overall, 18F-FDG PET/MRI has excellent diagnostic performance in staging/restaging BC patients.

8 Other PET Tracers Beyond 18F-FDG

Evangelista et al. [20] assessed the role of 18F-fluoroestradiol (18F-FES) PET in patients with BC. A pooled sensitivity of 82% (95%CI: 74–88%) and a pooled specificity of 95% (95%CI: 86–99%) for the evaluation of oestrogen receptor status in BC by 18F-FES PET were found, demonstrating a good accuracy of this method in this setting. Conversely, the pooled sensitivity and specificity of 18F-FES PET in predicting the response to hormonal therapy in patients with locally advanced or metastatic BC were unsatisfactory.

Deng et al. [21] evaluated the diagnostic performance of 18F-fluorothymidine (18F-FLT) PET and PET/CT for evaluating the response to chemotherapy in patients with BC. The pooled sensitivity and specificity of 18F-FLT PET in this setting were 77.3% (95%CI: 59.4–90%) and 68.5% (95%CI: 47.9–84.9%), respectively, with a moderate diagnostic accuracy.