Imaging of estrogen receptors using F-18-fluoroestradiol (FES) positron emission tomography (PET) may predict the response of advanced breast cancer to endocrine therapy by measuring regional target expression. According to research done by Dr. David A. Mankoff, associate professor of radiology in the UW School of Medicine, and his colleagues, imaging is ideally suited to quantify estrogen receptor expression because it avoids several factors that can make biopsy assays misleading in advanced disease.
It is known that breast tumors with high estrogen receptor expression are the most likely to respond to hormonal therapy. While receptor expression can be readily assessed with biopsied material, sampling errors may occur when patients have large or multi-site tumors. Furthermore, expression may change over time; recurrent breast cancer may have low or no estrogen receptor expression, even if the original primary tumor had high expression. These problems can be overcome using PET imaging to measure estrogen receptor expression at multiple sites and multiple times, reducing the risk of sampling errors.
Previous research by investigators at Washington University in St. Louis and by Mankoff and colleagues at the UW has shown that quantitative FES PET results correlate with estrogen receptor levels measured by assay. The St. Louis group has shown that the level of FES uptake in tumors predicts response to primary tamoxifen treatment. Guided by these earlier results, Mankoff and colleagues investigated FES PET as a predictive test for patients with more advanced breast cancer treated by a variety of hormonal agents.
So far, the results for 34 patients with a history of estrogen receptor positive tumors and recurrent or metastatic breast cancer have been analyzed. Over half of the patients had received prior adjuvant tamoxifen therapy and all had discontinued tamoxifen more than two months prior to the PET study, to prevent antagonism with the imaging agent. The participants in the study underwent FES PET close to the initiation of their therapy and subsequently received hormonal therapy without cytotoxic drugs for at least six months, unless there was clear tumor progression. More than 80 percent of the study participants were treated with aromatase inhibitors, which are being increasingly used in this patient population. Response was measured using clinical follow-up, tumor markers and a variety of other imaging studies. The responses were categorized as objective response, stable disease or progressive disease.
Qualitative imaging analysis of the FES PET studies showed that about 15 percent of patients had one or more FES-negative sites, suggesting loss of receptor. Only one of these patients responded to hormonal therapy. Quantitative image analysis showed that the level of FES uptake predicted response, with a significant association between FES uptake and subsequent response to hormonal therapy. No patient with low FES uptake had an objective response.
Mankoff said that these early results show the promise of FES PET for selecting breast cancer patients for hormonal therapy. Up to now, PET imaging has been used largely to help define the extent of tumor spread. This study is an example of how PET imaging can be used to assess specific targets for cancer treatment, with immediate applications to drug therapy trials and to patient care.