Is 99mTc-Sestamibi Scintimammography Complementary to Conventional Mammography for Detecting Breast Cancer in Patients with Palpable Masses? Omar Alonso, Teresa Massardo, Lucı´a B. Delgado, Jorge Horvath, Levent Kabasakal, Augusto Llamas-Olier, Khamza K. Maunda, Rosanna Morales, Ajit K. Padhy, and Uma Ravi Shankar Nuclear Medicine Center, Medical Oncology Department, Medicine Department, and Mammography Unit of Radiology Department, University of Uruguay, Montevideo, Uruguay; Nuclear Medicine Center, University of Chile, Santiago, Chile; Nuclear Medicine Department, Istanbul University, Istanbul, Turkey; Nuclear Medicine Department, National Cancer Institute, Bogota´, Colombia; Department of Nuclear Medicine, Ocean Road Cancer Institute, Dar es Salaam, Tanzania; Nuclear Medicine Department, Peruvian Institute of Nuclear Energy, Lima, Peru; Nuclear Medicine Section, Department of Human Health, International Atomic Energy Agency, Vienna, Austria; and Nuclear Medicine Department, Indraprastha Apollo Hospitals, New Delhi, India Key Words: 99mTc-sestamibi; scintimammography; breast The aim of this trial was to evaluate in developing countries from cancer different regions the diagnostic performance of 99mTc-sestamibi J Nucl Med 2001; 42:1614–1621 scintimammography (SM) in palpable breast lesions and to ver- ify the clinical usefulness of a joint evaluation with mammogra- phy and SM. Methods: From 10 countries, a total of 238 pa- tients with palpable breast masses (n ϭ 245) were included in this prospective multicenter trial. Prone SM was performed 10 Breast cancer is by far the most common malignancy min and 60–90 min (157 patients) after injection using an isotime among women worldwide, and 41% of all new cases are acquisition of 10 min. Mammography was assessed by the diagnosed in developing countries (1). In these countries, same dedicated imaging radiologist according to breast imag- 323,000 cases were detected in 1990, leading to 140,000 ing reporting and data system (BI-RADS) categories for malig- deaths (1,2). Furthermore, as the population increases and nancy and breast density. Masked SM findings and mammog- ages, the number of new cases in these countries is expected raphy findings were checked for a correlation with to increase dramatically (3). histopathology findings for excisional biopsy samples. Diagnos- tic values for breast cancer detection were calculated per le- Mammography represents the only validated imaging sion. Results: Histopathology revealed 189 cancerous lesions technique for breast cancer screening. Several randomized and 56 benign lesions. The sensitivity and specificity of SM were controlled trials have reported about a 30% mortality reduc- 0.83 and 0.77, respectively. SM diagnostic values did not de- tion in women older than 50 y using this procedure (4). pend on the incidence of breast cancer in the country of origin However, the technique is less reliable for detecting lesions or on the timing of imaging (early vs. delayed scans). On mam- in women younger than 50 y, in whom dense, glandular mography, the technique yielded a sensitivity and specificity of breasts are a common radiographic finding, yielding a false- 0.85 and 0.66, with 27 mammograms classified as BI-RADS category 1, 33 as category 2, 5 as category 3, 56 as category 4, negative rate of 25%–45% (5). Therefore, frequent delays and 124 as category 5. Thirty-seven lesions were considered to in the diagnosis of breast cancer are seen in this group and show increased radiologic density. No significant difference was are associated with significantly shorter survival (6). Fur- found in SM diagnostic values among different BI-RADS cate- thermore, the positive predictive value of mammography is gories or between the groups with low and high breast density. reported to be Ͻ40% (7), resulting in many unnecessary A sensitivity of 96% was calculated when SM and mammogra- biopsies. phy results were combined, with 75% of all false-negative mam- Since the publication of the encouraging results of mography findings classified as true-positive results by SM. 99m Conclusion: SM complements mammography in patients with Khalkhali et al. (8) for Tc-sestamibi scintimammography palpable masses and negative mammography findings. (SM), several investigators have reported on the clinical value of the technique and its possible complementary role to mammography for the evaluation of primary breast can- Received Feb. 22, 2001; revision accepted Jul. 13, 2001. cer (9–12). One of the proposed clinical indications for SM For correspondence or reprints contact: Omar Alonso, MD, Centro de Medicina Nuclear, Hospital de Clı´nicas,Avenida Italia s/n, Montevideo 11600, was palpable masses not clearly seen or classified as inde- Uruguay. terminate or benign on mammography (10,11). Therefore, a 1614 THE JOURNAL OF NUCLEAR MEDICINE • Vol. 42 • No. 11 • November 2001 multicenter trial sponsored by the International Atomic En- SM ergy Agency was set up to evaluate—in developing coun- Labeling and quality control of 99mTc-sestamibi were performed tries from different geographic regions—the diagnostic val- according to the manufacturer’s instructions (DuPont Pharmaceu- ues of SM in palpable breast lesions and the clinical ticals Co., Billerica, MA). The radiochemical purity of the radio- usefulness of an imaging protocol based on the joint appli- pharmaceutical was always Ն90%. 99mTc-sestamibi was injected through an indwelling catheter cation of mammography and SM. into the arm contralateral to the palpable breast lesion, and the catheter was then flushed with 10 mL saline. In patients with MATERIALS AND METHODS bilateral lesions, the injection was into a dorsal vein of the foot. The dose ranged from 740 to 1,110 MBq (20–30 mCi). Trial Design and Patients Planar scanning was started 10 min after injection of the tracer, The study was organized as a prospective open-label multi- beginning with the affected breast. Lateral views were acquired center trial. To be included, a patient had to be a nonpregnant with the patient lying prone, using a commercially available pad woman who had given informed consent and who had a palpable set (Pinestar Technology, Greenville, PA) designed to support the breast lesion as determined by an experienced surgeon, mammo- patient’s head, shoulders, and arms, allowing the imaged breast to grams obtained within 4 wk of SM, and a histopathologic report on depend while compressing the opposite breast. An anterior tho- an excisional biopsy specimen. Exclusion criteria included previ- racic view including both axillae was also obtained while the ous surgery for a palpable breast lesion, fine-needle biopsy within patient was supine with her arms raised behind her head. Delayed 1 wk before SM or core biopsy during the preceding 4 wk, prior imaging, 60–90 min after injection, was performed on 157 patients chemo- or radiotherapy, and lack of a histopathologic report. We (160 lesions). Images were acquired on a 256 ϫ 256 matrix, using received data for 346 patients from 10 countries in Africa, Asia, a 10% window centered on an energy peak of 140 keV. We used Europe, Latin America, and the Middle East: Chile (n ϭ 44), an isotime acquisition of 10 min for each view. A low-energy China (n ϭ 36), Colombia (n ϭ 39), Cuba (n ϭ 16), Greece (n ϭ high-resolution collimated gamma camera was used, with appro- 42), India (n ϭ 23), Peru (n ϭ 44), Tanzania (n ϭ 13), Turkey priate zooming for lateral views to include axillae, breast, and (n ϭ 52), and Uruguay (n ϭ 37). The age-standardized annual chest wall. The distance between the breast and the detector was incidence rates of breast cancer, as estimated in 1990 (1), in minimized. participating countries is summarized in Table 1 and ranges from 11.77 (China) to 87.59 (Uruguay), with a median of 29.19. Mammography The efficacy population of the trial consisted of 238 patients For all patients, mammography was performed using craniocau- (245 lesions, 7 patients with bilateral tumors), after 108 patients dal and mediolateral oblique views. Mammograms were sent to a were excluded because of inappropriate scintigraphy technique core-center dedicated breast-imaging radiologist, who evaluated (n ϭ 14), lack of mammograms (n ϭ 49), incomplete mammo- them according to the breast imaging reporting and data system grams with a recommendation for additional imaging (n ϭ 8), lack (BI-RADS) developed by the American College of Radiology of tissue diagnosis (n ϭ 20), or nonpalpable lesions (n ϭ 17). (Reston, VA) (13). The radiologist was unaware of histopathology The median age of the patients was 50 y (range, 19–84 y). In and SM findings, but physical examination data were available to 12% of patients, a family history of breast cancer was documented. him. Mammograms were considered positive for malignancy if the Oral contraceptives and hormone replacement therapy had been BI-RADS score was Ն4. When additional imaging was recom- used in 16% and 8% of patients, respectively. Prior surgery for mended, patients were scored as BI-RADS category 0 and ex- cancer of the contralateral breast had been performed on 4% of cluded from the efficacy population (n ϭ 8). Breast density was patients. Pre-, peri-, and postmenopausal status was present in also scored according to the BI-RADS system, with 1 ϭ entirely 41%, 7%, and 52% of patients, respectively. fatty, 2 ϭ fatty with scattered fibroglandular tissue, 3 ϭ hetero- geneously dense, and 4 ϭ extremely dense (13). Increased radio- logic density was documented for patients with scores of 3 or 4. TABLE 1 Masked Interpretation of SM Age-Standardized Annual Incidence Rates of Breast The SM films were read by 2 independent, experienced nuclear Cancer in Participating Countries medicine physicians who were unaware of the clinical status of the patient, physical examination findings, mammography findings, Country Incidence and histopathologic results. Initial and delayed images were scored China 11.77 separately by the readers, who did not know whether the images Tanzania 13.61 were from the same patient.