Early Reduction in Standardized Uptake Value After One Cycle of Neoadjuvant Chemotherapy Measured by Sequential FDG PET/CT is an Independent Predictor of Pathological Response of Primary Breast Cancer

To the Editor: F-fluorodeoxyglucose (FDG) levels on positron emission tomography (PET) reflect glucose metabolism in cancer cells (1). Currently, FDG PET combined with computed tomography (FDG PET ⁄ CT) has become employed as a non-invasive method for imaging glucose metabolism in tumors (2,3). The aim of the present study was to evaluate whether early metabolic changes after one cycle of neoadjuvant chemotherapy in FDG uptake evaluated by maximal standardized uptake value (SUVmax) could predict a pathological response of primary breast cancers. Thirty-two tumors in 30 patients having primary invasive breast cancer were investigated. All patients had received a standard neoadjuvant chemotherapy regimen comprising four cycles of epirubicine (90 mg ⁄ m) and cyclophosphamide (600 mg ⁄ m) on a triweekly basis and sequential use of 12 cycles of weekly paclitaxel (80 mg ⁄ m) (25 patients) or four cycles of triweekly docetaxel (60 mg ⁄ m) (five patients). The procedure of FDG PET ⁄ CT has been described (4). Sequential FDG PET ⁄ CT (Biograph LSO Emotion; 3D model, Siemens, Germany) was performed at the baseline (baseline PET ⁄ CT), after one cycle of chemotherapy (PET ⁄ CT2), after four cycles of chemotherapy (PET ⁄ CT3), and prior to surgery (PET ⁄ CT4). Tumors showing a 40% reduction or more in SUVmax on PET ⁄ CT2, when compared with the baseline PET ⁄ CT, were defined as metabolic responders and those showing a change of less than 40% in SUVmax were considered to be metabolic nonresponders (Fig. 1). Baseline characteristics of patients and tumors, determined by conventional modalities, are shown in Table 1. Baseline SUVmax was significantly higher in metabolic responders [10.2 ± 6.4 SD] than nonresponders (6.7 ± 3.1 SD) (p = 0.05). The percentage of tumors with nuclear grade 3 was significantly higher among the metabolic responders (71%) than among the nonresponders (16%) (p = 0.03). There were no significant differences between metabolic responders and nonresponders with regard to patient age, T-stage, nodal status, hormone receptor status, or HER2 status. The average degree of decrease in SUVmax at PET ⁄ CT2 in comparison with the baseline SUVmax was 57.9% (±11.7 SD) in metabolic responders and 10.3% (±15.7 SD) in metabolic nonresponders (p < 0.0001). Clinical response after completion of chemotherapy was measured using ultrasound or CT combined with FDG PET, and evaluated based on RECIST. On the basis of clinical response, five (71%) and two (29%) of the seven tumors with a metabolic response exhibited partial response (PR) and complete response (CR), respectively, while 18 (72%) of the 25 nonresponding tumors had PR. No nonresponding tumors showed CR. Metabolic responders showed a significantly excellent clinical response rate (100%) in terms of PR or CR in comparison with that (72%) for non-responding tumors (p = 0.001) (Table 2a). Histological criteria for assessment of therapeutic response were based on General Rules for Clinical and Pathological Recording of Breast Cancer 2008 (5). Among a total of 32 tumors, six (19%) and two (6%) were found to have grade 3, or pathological complete response (pCR), and to have grade 2b, or near pCR, where only a few residual invasive cancer cells were seen, respectively. Among the seven tumors with a metabolic response, three (43%) and two (29%) showed pCR and near pCR, respectively. Among the 25 tumors without metabolic response, Address corresopondence and reprint requests to: Hitoshi Tsuda, MD, PhD, Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan, or e-mail: hstsuda@ gmail.com.