Primary objective: To determine the utility of pre-treatment (16 alpha\[18-F\]-fluoroestradiol) FES-PET and routine (\[18-F\]-fluorodeoxy-D-glucose) FDG-PET in the prediction of response to hormone therapy using standard response criteria (RECIST) as gold standard in 100 primary tumor hormone positive (ER+) women with metastatic carcinoma of the breast.
We will measure standardized uptake ratio (SUV) for FDG and FES at baseline and correlate same to FDG/FES SUV ratio at disease relapse. We predict increased FDG/FES ratio at relapse and using the Pearson correlation coefficient will examine the regression equation slope as a measure of the changing ratio.
Twenty - forty patients will have core biopsy of accessible FDG positive and FES negative metastasis. Metastatic lesion immunohistochemistry (IHC) for ER will be compared to pretherapy FES result for concordance. With 80% agreement level for negative FES and negative core biopsy ER IHC 95% confidence limits (DI) are 56-94% for 20 and 64-90% for 40 patients respectively.
Proliferative index and tumor aggressiveness using IHC for Ki-67 and HER-2 respectively will be measured on primary tumor and biopsied metastatic lesion and correlated with metastatic disease response (RECIST).
Secondary objectives regarding HER-2 and Ki-67 IHC and response will be evaluated using Fisher's exact test for 2 X 2 tables for the 100 women and the 20-40 having core biopsy.
From the sensitivity and specificity determinations, calculated observed agreement between pretherapy FDG FES-PET ratio and RECIST will be 86% (95% CI 78-92%).
Assuming 40% response rate for 100 women receiving first, second or third line hormonal therapy and RECIST response as gold standard, we chose 80% sensitivity (95% CI 64-91%) and 90% specificity (95% CI 80-96%) as giving sufficiently robust data to warrant further studies.
