ANTICANCER RESEARCH 27: 2949-2952 (2007) Axillary Lymph Node Metastases Detection with 99mTc-sestamibi Scintimammography in Patients with Breast Cancer Undergoing Curative Surgery* FRANCO LUMACHI1, GUIDO FERRETTI2, MICHELE POVOLATO2, FRANCO BUI3, DIEGO CECCHIN3, MARIA CRISTINA MARZOLA3, PIETRO ZUCCHETTA3 and UMBERTO BASSO4 1Breast Surgery Unit, Department of Surgical and Gastroenterological Sciences, 3Nuclear Medicine Service, Department of Diagnostic Medical Sciences, University of Padua, School of Medicine, 35128 Padova; 2Nuclear Medicine Service, S.M. Misericordia Hospital, 33100 Udine; 4Division of Medical Oncology, Istituto Oncologico Veneto, IRCCS, 35128 Padova, Italy Abstract. Background: Axillary lymph node (AN) status is of the tumour (R=0.24, p<0.01) and number of positive the primary prognostic discriminant in patients with breast nodes (R=0.33, p<0.01). The sensitivity, specificity, positive cancer (BC). Although axillary dissection represents the predictive value, negative predictive value and accuracy of method of choice for obtaining such information, less SSM in detecting AN metastases were 81.4%, 91.0%, 84.2%, invasive procedures have been suggested. The aim of this 91.0% and 87.4%, respectively. The sensitivity was higher in study was to evaluate the usefulness of 99mTc-sestamibi patients with three or more positive nodes (27 out of 28, scintimammography (SSM) in detecting AN involvement in 96.4%), while in patients with two (n=25) or one (n=7) patients with confirmed primary BC undergoing surgery. positive nodes, the sensitivity decreased to 80% and 28.6%, Patients and Methods: A series of 159 consecutive women respectively. Conclusion: SSM may be useful in patients (median age 54 years, range 36-78 years) with confirmed BC undergoing surgery for BC when a preoperative assessment of undergoing curative surgery were enrolled in the study. Each axillary lymph node status is required. Unfortunately, the patient underwent SSM, from 4 to 12 days prior to surgery. sensitivity of SSM in detecting node metestases in patients According to the tumour staging, modified radical with BC is low when the number of involved nodes is two or mastectomy was performed in 41 (25.8%) patients, while 118 less. This suggests that other imaging techniques should be (74.2%) patients underwent breast conserving surgery with used is conjunction with SSM, with the aim of increasing dissection of the axilla. The results of SSM were compared both sensitivity and specificity. against the final histological evaluation of the axillary nodes. Results: The final pathology showed 33 (20.8%) pT1b, 90 Axillary lymph node (AN) status is the primary prognostic (56.6%) pT1c, and 36 (22.6%) pT2 breast carcinomas. The discriminant in patients with breast cancer (BC). greatest diameter of the tumour ranged from 8 to 30 mm Although axillary dissection represents the method of (median 16 mm). Sixty patients (37.7%) had axillary node choice for obtaining such information, less invasive metastases (N1), and 99 (60.3%) had negative nodes (N0). procedures have been suggested. Preoperative non- The age of the patients significantly correlated with both size surgical techniques include axillary ultrasonography (US) with or without US-guided fine-needle aspiration cytology (FNAC) or core-biopsy, fluorine-18-fluorodeoxyglucose (18-FDG) positron emission tomography (PET) and *Presented in part at the 12th European Cancer Conference 99m (ECCO 12), Copenhagen (Denmark), September 21-25, 2003. Tc-sestamibi scintimammography (SSM). The aim of this study was to evaluate the usefulness of Correspondence to: Prof. F. Lumachi, University of Padua, School SSM in detecting AN involvement in patients with of Medicine, Breast Surgery Unit, Department of Surgical and confirmed primary BC undergoing surgery. Gastroenterological Sciences, via Giustiniani 2, 35128 Padova, Italy. Tel: +39 049 821 1812, Fax: +39 049 656 145, e-mail: Patients and Methods [email protected] Study population. A series of 159 consecutive women (median age Key Words: Breast cancer, scintimammography, axillary node 54 years, range 36-78 years) with BC confirmed by FNAC, core metastases. biopsy or open biopsy undergoing curative surgery were enrolled 0250-7005/2007 $2.00+.40 2949 ANTICANCER RESEARCH 27: 2949-2952 (2007) Table I. Histological type of the tumour, and pathological staging at final Table II. Results of 99mTc-sestamibi scintimammography in detecting pathology. axillary node metastases. Characteristics N0 % N1 % Overall % TP FP TN FN Sensitivity Specificity PPV NPV Accuracy Overall patients 99 62.3% 60 37.7% 159 48 9 91 11 81.4% 91.0% 84.2% 91.0% 87.4% Histological type TP=true-positives, FP=false-positives, TN=true-negatives, FN=false- Infiltrating ductal 83 83.8% 56 93.3% 139 87.4% negatives, PPV=positive predictive value, NPV=negative predictive Infiltrating lobular 7 7.1% 1 1.7% 8 5.0% value. Medullary 3 3.0% 0 - 3 1.9% Other and mixed 6 6.1% 3 5.0% 9 5.7% Table III. Main differences between patients with true-positive and false- Pathological tumour stage negative scintimammorgaphy. pT1b 31 31.3% 2 3.3% 33 20.8% pT1c 66 66.7% 24 40.0% 90 56.6% Characteristics True-positives p-value False-negatives pT2 2 2.0% 34 56.7% 36 22.6% Number of patients 48 - 11 N0=number of patients with negative nodes, N1=number of patients Age (years) 58.8±7.7 <0.001 48.6±10.3 with involved nodes. Size of the tumour (mm) 21.2±4.5 0.06 18.2±5.4 Number of removed nodes 19.9±2.1 0.77 19.7±2.0 Number of positive nodes 3.0±1.2 <0.001 1.6±0.7 in the study. In patients with non-palpable masses the biopsy was pT2=21-50 mm; pN0=no lymph node metastases, pN1=metastases performed using a wire needle localization, under US or in at least one axillary node (5). stereotactic guidance. There were 44 (27.7%) premenopausal and A positive result of SSM identified the presence of one or more 115 (73.3%) post-menopausal women. metastatized AN. Sensitivity was defined as true-positives (TP)/TP Once they had given informed consent, each patient underwent + false-negatives (FN), specificity as true-negatives (TN)/TN + SSM, from 4 to 12 days prior to surgery. According to the tumour false-positives (FP), positive predictive values (PPV) as TP/(TP + staging, modified radical mastectomy was performed in 41 (25.8%) FP), negative predictive values (NPV) as TN/(TN + FN), and patients, while 118 (74.2%) patients underwent breast conserving accuracy as (TN + TP)/overall patients. surgery with AN dissection. The reported data are in part expressed as mean±standard The greatest diameter (size) of the tumour (pT) was deviation (SD). The Mann-Whitney U-test and the Pearson’s measured by the pathologist, and the final diagnosis was correlation coefficient (R) calculation were used for the obtained by routinely stained serial sections (1 mm of comparison of qualitative variables in the case of non-normal thickness). The results of SSM were compared against final distribution and to evaluate the linear relationship between pairs histological evaluation of AN. of variables, respectively. Comparisons between groups were performed using the Student’s t-test, when required. The 99mTc-sestamibi scintimammography. According to the procedure differences were considered significant at a p-value <0.05. guidelines suggested by The Society of Nuclear Medicine (SNM), a single dose (750 MBq) of 99mTc-sestamibi (methoxyiso- Results butylisonitrile) was injected in the arm contralateral to the side of the lesion (1). A triple head gamma camera (Philips Irix) equipped with a parallel-hole low-energy high-resolution collimator The size of the tumours ranged from 8 mm to 30 mm (resolution 7.5 mm at 10 cm), a 140 keV (10% window) energy (median 16 mm). Table I reports the histological type of the setting and a 256x256 matrix was used. tumours, and the pathological staging at final pathology. To improve the visualization of the axilla, patients were in prone Sixty patients (37.7%) had axillary node metastases (N1) position, with arms raised above the head, and the images were acquired 5-10 min after intravenous injection of the radio- and 99 (60.3%) had negative nodes (N0). The average pharmaceutical (2). number of removed nodes was 19.9±2.1 and the mean Planar (prone lateral, anterior and posterior oblique) images number of positive nodes was 2.7±1.2. combined with SPECT (128 x 128 matrix, 64 steps, 30 sec/step, The age of the patients significantly correlated with both size 180Æ acquisition) images were obtained. A focal uptake of the of the tumour (R=0.24, F=9.55, p=0.002) and number of 99m Tc-sestamibi, and a mass-to-background ratio of more than 1.4 positive nodes (R=0.33, F=7.11, p<0.009). As expected, there was considered as a positive result, as previously reported (3, 4). was a direct relationship (R=0.31, F=6.08, p=0.016) between Definitions and statistical analysis. The tumours were classified the size of the tumour and the number of positive nodes. according to the TNM classification: pT1b=6-10 mm in size The sensitivity, specificity, PPV, NPV, and accuracy of (greatest diameter measured by the pathologist), pT1c=11-20 mm, SSM in detecting AN metastases are reported in Table II. 2950 Lumachi et al: Axillary Scintimammography in Breast Cancer Patients with false-negative SSM were significantly (p<0.01) Acknowledgements younger than those in whom the imaging technique correctly detected involved AN (Table III). Moreover, the The authors are grateful to Dr. Annamaria Grigio and Miss number of removed AN did not differ (p=NS) between Federica De Lotto for help in writing the manuscript and for patients with true-positive and false-negative SSM, while the reviewing the English.