Accurate recurrence risk assessment in hormone receptor positive, HER2/neu negative breast cancer is critical to plan precise therapy. CanAssist Breast (CAB) assesses recurrence risk based on tumor biology using artificial intelligence-based approach. We report CAB risk assessment correlating with disease outcomes in multiple clinically high- and low-risk subgroups. In this retrospective cohort of 925 patients [median age-54 (22-86)] CAB had hazard ratio (HR) of 3 (1.83-5.21) and 2.5 (1.45-4.29), P = 0.0009) in univariate and multivariate analysis. CAB's HR in sub-groups with the other determinants of outcome, T2 (HR: 2.79 (1.49-5.25), P = 0.0001); age [< 50 (HR: 3.14 (1.39-7), P = 0.0008)]. Besides application in node-negative patients, CAB's HR was 2.45 (1.34-4.47), P = 0.0023) in node-positive patients. In clinically low-risk patients (N0 tumors up to 5 cms) (HR: 2.48 (0.79-7.8), P = 0.03) and with luminal-A characteristics (HR: 4.54 (1-19.75), P = 0.004), CAB identified >16% as high-risk with recurrence rates of up to 12%. In clinically high-risk patients (T2N1 tumors (HR: 2.65 (1.31-5.36), P = 0.003; low-risk DMFS: 92.66 ± 1.88) and in women with luminal-B characteristics (HR: 3.24; (1.69-6.22), P < 0.0001; low-risk DMFS: 93.34 ± 1.34)), CAB identified >64% as low-risk. Thus, CAB prognostication was significant in women with clinically low- and high-risk disease. The data imply the use of CAB for providing helpful information to stratify tumors based on biology incorporated with clinical features for Indian patients, which can be extrapolated to regions with similarly characterized patients, South-East Asia.

The aim of this study was to evaluate the incremental value of cocktail 18F-FDG/18F-NaF PET/CT over 18F-FDG PET/CT alone for detection of skeletal metastases in breast cancer patients. Seventy patients with locally advanced/recurrent breast cancer were prospectively included. All patients underwent whole-body 18F-FDG PET/CT and cocktail 18F-FDG/18F-NaF PET/CT within a span of 1 week. Both studies were evaluated to detect presence of skeletal/marrow metastases on PET/CT images by 2 nuclear medicine physicians. Clinical and radiological correlation/follow-up was used as criterion standard. Of 70 patients, 50 (71.0%) had locally advanced breast cancer, and 20 had recurrent breast cancer. On patient-wise analysis, both cocktail PET/CT and 18F-FDG PET/CT identified skeletal/marrow lesions in 23 (32.8%) of 70 patients. In 8 patients (11.4%), only cocktail PET/CT identified skeletal/marrow lesions, whereas 18F-FDG PET/CT was negative. In the rest of the 39 patients (55.8%), no skeletal/marrow lesion was identified on both scans. Good correlation was noted between cocktail PET/CT and 18F-FDG PET/CT results (r = 0.785, P < 0.0001). Cocktail PET/CT detected lesions in significantly more number of patients than 18F-FDG PET/CT alone (P = 0.007). On lesion-wise analysis, cocktail PET/CT detected more number of lesions in 20 patients as compared with 18F-FDG-PET/CT alone. Both scans detected same number of lesions in the rest of 11 patients with positive findings. A total of 32 additional lesions were identified on cocktail PET/CT imaging as compared with 18F PET/CT alone (P < 0.0001). Cocktail 18F-FDG and 18F-NaF PET/CT is superior to 18F-FDG PET/CT alone for the detection of skeletal/marrow metastases in breast cancer. It can be a better alternative to 18F-FDG PET/CT alone in facilities where both tracers are available.

PURPOSE The aim of the study was to radiolabel, characterize, and perform in vitro and in vivo assessment of Technetium-99m (Tc-99m) tamoxifen for screening ER expressing lesions in breast cancer patients. METHODS In this study, tamoxifen has been radiolabeled with Tc-99m via Tc-99m-tricarbonyl core. The characterization and quality control tests of Tc-99m-tamoxifen were performed. In vitro recep- tor binding and blocking studies were performed in both positive control (MCF-7) and negative control cell lines (MDA-MB-231). Normal biodistribution studies were performed in female Wistar albino rats. The pilot clinical studies were performed in 4 ER-expressing breast cancer patients. Of the 4 patients, 1 was on tamoxifen therapy. All 4 patients had also undergone Fluorine-18 fluorodeoxyglucose (F-18-FDG) positron emission tomography/computed tomography. RESULTS Tamoxifen was radiolabeled with Tc-99m via Tc-99m-tricarbonyl core with more than 95% radio- chemical yield. Mass spectra showed a peak corresponding to the molecular weight of Tc-99m- tricarbonyl and Tc-99m-tamoxifen. The site of binding of Tc-99m-tricarbonyl with tamoxifen was determined by proton nuclear magnetic resonance. The Tc-99m-tamoxifen showed 30% binding with MCF-7 and only 1%-2% receptor binding with MDA-MB-231 cell lines. Also, the percentage of receptor binding was drastically reduced (up to 72%) when ER was saturated with 50 times the excess molar ratio of unlabeled tamoxifen. In a pilot patient study, Tc-99m-tamoxifen uptake was observed in primary and metastatic lesions. However, no uptake was observed in a patient who was on tamoxifen therapy. The uptake of F-18-FDG was noted in all the patients. CONCLUSION Tamoxifen was radiolabeled with an in-house-synthesized Tc-99m-tricarbonyl core. The radio- labeled complex has been characterized and evaluated for receptor specificity in in vitro and in vivo studies. Also, this is the first clinical study using Tc-99m-tamoxifen for imaging ER. More patients need to be evaluated to further explore the role of Tc-99m-tamoxifen in ER-expressing lesions.