Characterization of Circulating Tumor Cells (CTC) From Patients With Metastatic Breast Cancer Using the CTC-Endocrine Therapy Index

Patients with estrogen receptor (ER) positive metastatic breast cancer (MBC) starting their first line of endocrine therapy (ET) only have a 30-50% chance of receiving clinical benefit. For the other 50-70% of patients, ET is ineffective and these patients should probably be treated with chemotherapy, as is done for ER negative patients. More importantly, in nearly every clinical trial of ET in ER positive, MBC patients, between 15-30% of enrolled patients progress in the first 2-3 months, regardless of whether they are receiving first or later lines of ET. Currently there is no validated method to identify which ER positive MBC patients will be refractory to ET. Therefore, almost all ER positive patients are treated with serial endocrine therapies before switching to chemotherapy. The investigators propose that a subset of these patients would be better served with chemotherapy, in spite of its increased toxicity profile, rather than delaying chemotherapy during a several month trial of ineffective, albeit less toxic, ET. To try and predict benefit from or resistance to ET, an index (the CTC-ETI) has been created that takes into account the number of CTC (which is prognostic) as well as the phenotype of the CTC, based on the hypothesis that relative levels of ER and Bcl-2 (high=benefit) and HER2 and Ki67 (high=resistance) are predictive of ET responsiveness or resistance. Although the preliminary data demonstrate the ability to detect, enumerate, and characterize CTC utilizing the CellSearch® System, the purpose of the current study is to establish proof of principle that these 4 markers can be used to generate a CTC-ETI which can be performed at baseline from patients enrolled at different centers, and that baseline CTC-ETI predicts relative outcome for patients with ER positive MBC starting a new ET, and can be monitored in such patients during ET. Successful completion of this study will set the stage for a larger, definitive study designed to demonstrate the clinical utility of a "refined" CTC-ETI in patients with ER positive, HER2 negative MBC.