Role of fluorodeoxyglucose positron emission tomography in the staging of patients with breast cancer candidated to surgery
Authors: A. Cardillo, C. De Cicco, G. Paganelli, R. Ghisini, G. Peruzzotti, A. Balduzzi, A. Goldhirsch, N. Rotmensz, P. Veronesi, A. Luini, M. Intra, M. Colleoni
Journal: Annals of Oncology (2006)

Medical efforts and financial expenditures devoted to initial breast cancer staging represent a heavy burden on health care resources. Staging the disease accurately is considered to be important before surgery, in order to spare unnecessary treatment to patients with metastatic disease [1.Norum J. Andreassen T. Screening for metastatic disease in newly diagnosed breast cancer patients. What is cost-effective?.Anticancer Res. 2000; 20: 2193-2196PubMed Google Scholar]. The role of 2-[fluorine-18]fluoro-2-deoxy-D-glucose–positron emission tomography (FDG-PET) in the staging has been studied recently [2.Van der Hoeven J.J. Krak N.C. Hoekstra O.S. et al.18F-2-fluoro-2-deoxy-d-glucose positron emission tomography in staging of locally advanced breast cancer.J Clin Oncol. 2004; 22: 1253-1259Crossref PubMed Scopus (113) Google Scholar]. Initial results on the role of FDG-PET in addition to the standard work-up of patient with LABC (locally advanced breast cancer) indicated that FDG-PET may contribute to proper stratification between LABC patients and those who are affected by metastatic disease. Preliminary results in a small group of 42 high-risk women with primary or recurrent breast cancer, where FDG-PET and conventional staging methods were compared, FDG-PET revealed additional confirmed lesions in five patients, leading to a significant change in patient management [3.Bellon J.R. Livingston R.B. Eubank W.B. et al.Evaluation of the internal mammary lymph nodes by FDG-PET in locally advanced breast cancer (LABC).Am J Clin Oncol. 2004; 27: 407-410Crossref PubMed Scopus (92) Google Scholar]. This, therefore, prompted us to ascertain the relevance of FDG-PET in detecting asymptomatic metastases in the perioperative staging of breast cancer patients. A retrospective review of 228 patients with operable breast cancer staged according to the TNM (tumor–node–metastasis) staging system as T1–3, N0–2 and all referred to the European Institute of Oncology (EIO) during the period from September 2002 to April 2005, was performed. Patients had histologically proven breast cancer, with definitive breast surgery, staging and preoperative PET scan performed at the EIO. PET scan was performed 1–15 days before surgery. Images were obtained 45 min after i.v. injection of 5.3 MBq/kg of [18F]-FDG, using a PET/computed tomography scanner. Stage of disease was defined by standard pathological examinations. All patients had conventional staging (chest X-ray, liver ultrasound and bone scan). Patient characteristics are showed in Table 1. All were asymptomatic at the time of PET scan. The primary tumors were identified in 179 (78%) cases. The positivity rate was different for lobular versus ductal invasive breast cancer patients (60 versus 79%, P = 0.08) and for grade 1 tumors versus grade 2–3 tumors (56% versus 82%, P = 0.003). Thirteen patients (6%) had an uptake at distant sites (bone, four; liver, two; thyroid, two; pleura, one; internal mammary node, one; contralateral breast, one; with two patients having no specific uptake in the lung and abdomen), with standard staging investigations negative. Further examinations confirmed the presence of metastasis in only two cases (Table 2). As shown in Table 2, a magnetic resonance imaging confirmed the presence of multiple bone lesions not detected by bone scan. In this patient multiple uptakes were present at the FDG-PET both in the bone and bone marrow. These results compare favorably with results achieved with bone scan and do not support previously published data, indicating a possible inferiority of FDG-PET in the detection of bone metastases, in particular due to possible missing blastic lesions [4.Wahl R.L. Current status of PET in breast cancer imaging, staging, and therapy.Semin Roentgenol. 2001; 36: 250-260Crossref PubMed Scopus (76) Google Scholar]. In conclusion, our results support a role for PET staging in particular for those patients whose tumors are of high grade and of ductal histology, as previously published [5.Buck A.K. Schirrmeister H. Mattfeldt T. Reske S.N. Biological characterisation of breast cancer by means of PET.Eur J Nucl Med Mol Imaging. 2004; 31: 80-87Crossref PubMed Scopus (83) Google Scholar]. Since baseline PET scans had a cost of &euro;1000 each, which compares with &euro;635.68 of conventional staging costs, the cost-effectiveness for the introduction of PET in the staging of patients with operable breast cancer should be further studied in larger trials.Table 1Major patients' characteristicsNumber of patientsPet positive in breast and/or axillary nodes (%)Pet positive in other sites (%)US, chest X-ray, bone scan positive at distant sites (%)Total228179 (78)13 (6)0 (-)PT1 node negative8854 (61)8 (9)0 (-)PT2–3 node negative3935 (90)0 (-)0 (-)PT1 node positive4839 (81)0 (-)0 (-)PT2–3 node positive5351 (96)5 (9)0 (-)ER/PgR negativeaER and/or PgR negative: 0% of the cells.6551 (78)4 (6)0 (-)ER/PgR other163128 (79)9 (5.5)0 (-)Grade 13218 (56)1 (3)0 (-)Grade 2–3196161 (82)12 (6)0 (-)Ductal invasive184146 (79)13 (7)0 (-)Lobular invasive2012 (60)0 (-)0 (-)Other histology2421 (88)0 (-)0 (-)ER, estrogen receptor; PET, positron emission tomography; PgR, progesteron receptor.a ER and/or PgR negative: 0% of the cells. Open table in a new tab Table 2Site of PET uptake and diagnosisPatient IDSite of PET uptakeFurther work-upFinal ReportFollow-up (months)1Internal mammary nodesBiopsyMetastasis17.02Bone (multiple lesions)MRIMetastasis24.93LiverCT scanNo metastasis27.34BoneMRINo metastasis29.95BoneMRINo metastasis20.36ThyroidFNABNo metastasis27.37ThyroidUSNo metastasis22.18Breast controlateralBiopsyNo metastasis24.49LiverMRI and USNo metastasis28.810BoneBone scanNo metastasis19.611PleuraCT scanNo metastasis18.9CT, computed tomography; FNAB, fine needle aspiration biopsy; MRI, magnetic resonance imaging; PET, positron emission tomography; US, ultrasound. Open table in a new tab Medical efforts and financial expenditures devoted to initial breast cancer staging represent a heavy burden on health care resources. Staging the disease accurately is considered to be important before surgery, in order to spare unnecessary treatment to patients with metastatic disease [1.Norum J. Andreassen T. Screening for metastatic disease in newly diagnosed breast cancer patients. What is cost-effective?.Anticancer Res. 2000; 20: 2193-2196PubMed Google Scholar]. The role of 2-[fluorine-18]fluoro-2-deoxy-D-glucose–positron emission tomography (FDG-PET) in the staging has been studied recently [2.Van der Hoeven J.J. Krak N.C. Hoekstra O.S. et al.18F-2-fluoro-2-deoxy-d-glucose positron emission tomography in staging of locally advanced breast cancer.J Clin Oncol. 2004; 22: 1253-1259Crossref PubMed Scopus (113) Google Scholar]. Initial results on the role of FDG-PET in addition to the standard work-up of patient with LABC (locally advanced breast cancer) indicated that FDG-PET may contribute to proper stratification between LABC patients and those who are affected by metastatic disease. Preliminary results in a small group of 42 high-risk women with primary or recurrent breast cancer, where FDG-PET and conventional staging methods were compared, FDG-PET revealed additional confirmed lesions in five patients, leading to a significant change in patient management [3.Bellon J.R. Livingston R.B. Eubank W.B. et al.Evaluation of the internal mammary lymph nodes by FDG-PET in locally advanced breast cancer (LABC).Am J Clin Oncol. 2004; 27: 407-410Crossref PubMed Scopus (92) Google Scholar]. This, therefore, prompted us to ascertain the relevance of FDG-PET in detecting asymptomatic metastases in the perioperative staging of breast cancer patients. A retrospective review of 228 patients with operable breast cancer staged according to the TNM (tumor–node–metastasis) staging system as T1–3, N0–2 and all referred to the European Institute of Oncology (EIO) during the period from September 2002 to April 2005, was performed. Patients had histologically proven breast cancer, with definitive breast surgery, staging and preoperative PET scan performed at the EIO. PET scan was performed 1–15 days before surgery. Images were obtained 45 min after i.v. injection of 5.3 MBq/kg of [18F]-FDG, using a PET/computed tomography scanner. Stage of disease was defined by standard pathological examinations. All patients had conventional staging (chest X-ray, liver ultrasound and bone scan). Patient characteristics are showed in Table 1. All were asymptomatic at the time of PET scan. The primary tumors were identified in 179 (78%) cases. The positivity rate was different for lobular versus ductal invasive breast cancer patients (60 versus 79%, P = 0.08) and for grade 1 tumors versus grade 2–3 tumors (56% versus 82%, P = 0.003). Thirteen patients (6%) had an uptake at distant sites (bone, four; liver, two; thyroid, two; pleura, one; internal mammary node, one; contralateral breast, one; with two patients having no specific uptake in the lung and abdomen), with standard staging investigations negative. Further examinations confirmed the presence of metastasis in only two cases (Table 2). As shown in Table 2, a magnetic resonance imaging confirmed the presence of multiple bone lesions not detected by bone scan. In this patient multiple uptakes were present at the FDG-PET both in the bone and bone marrow. These results compare favorably with results achieved with bone scan and do not support previously published data, indicating a possible inferiority of FDG-PET in the detection of bone metastases, in particular due to possible missing blastic lesions [4.Wahl R.L. Current status of PET in breast cancer imaging, staging, and therapy.Semin Roentgenol. 2001; 36: 250-260Crossref PubMed Scopus (76) Google Scholar]. In conclusion, our results support a role for PET staging in particular for those patients whose tumors are of high grade and of ductal histology, as previously published [5.Buck A.K. Schirrmeister H. Mattfeldt T. Reske S.N. Biological characterisation of breast cancer by means of PET.Eur J Nucl Med Mol Imaging. 2004; 31: 80-87Crossref PubMed Scopus (83) Google Scholar]. Since baseline PET scans had a cost of &euro;1000 each, which compares with &euro;635.68 of conventional staging costs, the cost-effectiveness for the introduction of PET in the staging of patients with operable breast cancer should be further studied in larger trials. ER, estrogen receptor; PET, positron emission tomography; PgR, progesteron receptor. CT, computed tomography; FNAB, fine needle aspiration biopsy; MRI, magnetic resonance imaging; PET, positron emission tomography; US, ultrasound.