For Women With Estrogen Positive Metastatic Breast Cancer Discordance of Pre-treatment FDG-PET and FES-PET in Addition to Presence of Ki-67 and Human Epidermal Growth Factor 2 (HER-2) Overexpression Will Predict for Hormone Refractory Disease When Compared to Standard Response Criteria
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
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
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
Time Perspective: Prospective
K. Tonkin, MD
Alberta Health Services
Canada: Health Canada