This revised proposal evaluates the utility of PET scanning, in particular PET scanning using 2-deoxy-2-[F-18]-fluoro-d-glucose (FDG), in the diagnosis, staging and monitoring of the therapy of patients with breast cancer. In initial studies, large primary breast carcinomas will be imaged to assess blood flow (using 0-15 water) and glucose utilization (using FDG) at time points before, during and at the conclusion of combined chemo-hormonotherapy. These studies are expected to demonstrate that alterations in tumor glucose metabolism and blood flow occur well before tumor shrinkage in effective therapy, and thus may serve as early predictors of the effectiveness or ineffectiveness of tumor therapy. The studies should also allow us to correlate the extent of FDG uptake with the degree of aggressiveness of the tumor as measured by DNA ploidy, morphology, protooncogene protein expression and time from diagnosis until recurrence. We also will sequentially examine tumor blood flow and FDG uptake kinetics in metastatic foci of breast cancer in patients undergoing chemotherapy or hormonal therapy to determine if PET scans can serve as an accurate early predictor of the ultimate tumor response. FDG uptake kinetics, in tumors with biopsy-proven estrogen receptor status will be assessed during single-agent estrogen or anti-estrogen treatment regimens, to determine if FDG uptake correlates with receptor status and response to treatment. FDG uptake kinetics into known and suspected newly-diagnosed skeletal metastases that are visible on bone scan as well as into boney metastases undergoing treatment will be studied in an effort to determine if FDG can improve upon the accuracy of Tc99m MDP bone scanning technique for earlier and more specific detection of treatment-induced responses in boney metastases. Biopsy proof of scan findings will be obtained whenever possible. We will also begin to study the accuracy of the """"""""PET FDG mammogram"""""""" in detecting tumor foci in breasts, particularly those breasts that have equivocal physical exam and mammographic findings (or which are difficult to examine mammographically due to their density-either due to glandular tissue, scar, or radioopaque prostheses), and which are scheduled for biopsy. We also will explore the accuracy of FDG PET scanning in the assessment of the metastatic cancer involvement in the axillary lymph nodes in patients with newly-diagnosed breast carcinoma who are scheduled for surgical axillary dissections. Through these studies we expect to determine if 1) treatment-induced changes in FDG uptake or tumor blood flow can serve as early predictors of the success or failure of tumor therapy and 2) if PET scanning can better detect, stage and monitor breast cancer than other methods.
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