Although the degree of uptake varies depending on histological type, tumor grade, and phenotype, the overwhelming majority of breast tumors are 18
The aim of this prospective study was to examine the yield of 18FDG-PET-CT as a single examination in a large population of patients with clinical stage II and III breast cancer and in each specific substage. Therefore, nuclear physicians were blind to all conventional imaging studies that could have been ordered in parallel (eg, BS, chest x-ray, CT, liver ultrasound).
Stage modification due to detection of N3 disease (infraclavicular, supraclavicular, or internal mammary nodes) and/or distant metastases occurred in 4.5% of stage IIA patients, 16.1% of stage IIB patients, 31.7% of stage IIIA patients, 51.4% of stage IIIB patients, and 47.1% of stage IIIC patients. We suggested that PET-CT might be justified starting with stage IIB.
The overall low yield in stage IIA (4.5%) might challenge the use in this group if considering cost of 18
FDG-PET-CT imaging, increased patient anxiety, potential for delaying care, risk of invasive procedures stimulated by false-positive results, and exposure to ionizing radiation (21
). Stage IIA was mainly represented by T2N0 disease; only two patients had T1N1 disease. Sentinel node-positive patients were not included.
The rate of distant metastases uncovered with 18
FDG-PET-CT showed a steady increase across subgroups: 2.3% in stage IIA patients, 10.7% in stage IIB patients, 17.5% in stage IIIA patients, 36.5% in stage IIIB patients, and 47.1% in stage IIIC patients. Within stage IIIA, the risk differed between patients with T3N1 disease and those with N2 disease (, ). Interestingly, management recommendations would usually distinguish between these entities (22
One advantage of 18
FDG-PET-CT is its ability to examine extra-axillary nodes, chest, abdomen, and bone in a single session (4–12
). We observed a higher accuracy for 18
FDG-PET-CT compared with planar BS, which is in agreement with reports from Fuster et al. (8
) and Morris et al. (23
). Not all patients in the present study received chest diagnostic CT or abdominal-pelvic diagnostic CT (or magnetic resonance imaging), making a comparison for other sites of involvement difficult.
The impact of 18FDG-PET-CT findings on prognosis was examined in patients with clinical stage IIB or higher disease. The 3-year DSS was statistically significantly shorter in women who were scored M1 on PET-CT in comparison with those scored M0 (57% vs 88%; P < .001). This impact was also apparent in the subset of patients with stage IIB and primary operable IIIA (T2N1/T3N0/T3N1).
Besides prognostic value, the information from 18
FDG-PET-CT can be helpful in adapting treatment. Early detection of distant metastases might lead to refinement in the type of systemic treatment. It can also lead to local treatments in some patients (eg, liver surgery, radiofrequency ablation, radiation therapy to bone metastases). Detection of N3 disease might influence the extent of surgery and the design of radiation fields (24
In the absence of distant metastases, the prognostic impact of N3 disease did not reach statistical significance (P
=.16). A possible explanation could be that patients with N3-detected nodes received a more aggressive treatment with curative intent (). Patients with supraclavicular metastases were previously categorized as stage IV. These patients are potentially curable in the era of multimodality imaging and therapy (24–26
In a multivariable analysis, two independent prognostic variables were highly statistically significant: M1-disease on 18
FDG-PET-CT and a triple-negative phenotype. Findings that patients with TNBC are at high risk, even in the absence of distant metastases on initial PET-CT staging, reinforces the feeling that monitoring tumor response during neoadjuvant chemotherapy is needed (27
The proportion of extra-skeletal metastases in patients with TNBC was high (Table 2
). TNBC is more likely to metastasize to viscera, particularly lungs, brain, and liver (28
). In that regard, it is important to note that some patients with isolated brain metastases might have escaped detection.
Our study has some limitations, mainly resulting from difficulties in performing confirmatory biopsies of distant metastases seen on 18FDG-PET-CT in every case. The remarkable progression in the yield of 18FDG-PET-CT with advancing clinical stage and the correlation between PET-CT findings and prognosis are strong arguments that the overwhelming majority of patients classified as M+ on the basis of 18FDG-PET-CT have true-positive metastases.
Another limit is the single-institution design. These results thus need to be validated in independent settings. We checked that our series was representative. Phenotype distribution (TNBC, 27%; HER2-enriched, 20%; estrogen receptor–positive and HER2-negative, 51%) is roughly similar to other reports (29
In conclusion, 18FDG-PET-CT has substantial yield in breast cancer patients with clinical stage IIB or higher breast cancer, and findings from this examination have prognostic value. It is hoped that the information provided at initial staging might lead to better management of these patients who account for the largest mortality rate from breast cancer.