metastatic breast cancer continues to be almost uniformly fatal ; however , improvements in survival in developed countries have been documented . this improvement can be attributed to better therapeutic and diagnostic tools for disease management . yet , there is a limited array of tools for a noninvasive assessment of metastatic breast cancer , which includes imaging [ computed tomography ( ct ) scans , bone scintigraphy , positron emission tomography ( pet ) , and magnetic resonance imaging ] and measurement of serum tumor marker concentration in the peripheral blood . one challenge to the introduction of new clinical tools is to determine their best use in clinical decision making . in other words , facilitating the integration of clinical information from these new assessments into the clinical workflow and decision making is critical . circulating tumor cells ( ctcs ) are useful as an indicator of prognosis both initially and after therapy . multiple studies have shown that patients with 5 ctcs/7.5 ml of peripheral blood have a worse prognosis for survival than patients with < 5/7.5 ml . the concentration of ctcs shed by solid tumors and detected in the peripheral circulation correlates with relapse and survival in multiple types of cancer [ 3 , 4 , 5 , 6 , 7 , 8 ] . a system for measuring ctc concentration in peripheral blood to monitor metastatic breast , colon , and prostate cancer has been cleared by the united states food and drug administration and is now commercially available for clinical use ( cellsearch , janssen diagnostics , llc ) . however , how to best integrate this new information on disease status with existing measurements of disease prognosis and progression in clinical decision making remains empiric . here we present a case of metastatic breast cancer in which ctc information was used to help resolve discrepancies between more conventional assessments to improve patient care . pathology demonstrated estrogen - receptor - positive and progesterone - receptor - positive disease . at that time , she was treated with breast - conserving surgery , followed by radiation therapy . , the patient was diagnosed with distant recurrence of her disease localized to the right femur . after an initial response , the chemotherapy was discontinued and the patient was placed on maintenance letrozole and pamidronate . the patient was diagnosed with progressive disease based on imaging done in november 2006 . her therapy was switched to fulvestrant plus zoledronic acid based on the imaging study ( table 1 ) . an initial ctc measurement using the cellsearch system resulted in a determination of 1/7.5 ml ( fig . 1 ) . a repeat ctc measurement in february 2007 again returned a value of 1/7.5 ml . in april 2007 , pet / ct imaging revealed metastatic deposits in the liver and bone , suggesting progressive disease ; however , based on the low ctc count in february the decision was made to not change treatment . repeat imaging in july 2007 showed a partial response ( pr ) in the liver and bone lesions ( fig . thus , although the patient 's ctc count had risen to 6/7.5 ml and initial tumor marker measurements were elevated ( 497 u / ml for ca 27.29 and 58 ng / ml for cea ) , therapy with fulvestrant plus zoledronic acid was continued based on a lack of changes in imaging studies and continued good performance status ( table 1 ) . in october 2007 , the patient 's ctc count remained at 6/7.5 ml , while her ca 27.29 had risen to 520 u / ml . in december 2007 , the ctc count had declined to 0 and tumor marker levels were stable . pet / ct imaging demonstrated improvement in the liver lesions and a mixed response in the bone lesions ( fig . radiation therapy was given to the metastatic sites identified as active by increased standardized uptake values from the pet / ct imaging in december 2007 . the following february , ctc levels remained below 5/7.5 ml and tumor markers were elevated and stable . ctcs were absent from the patient 's peripheral blood in a measurement in april 2008 . in may 2008 , her ctc level had risen from 0 in april to 9/7.5 ml , and ca 27.29 had risen to 1,371 u / ml , confirming progressive disease ( fig . the patient 's therapy was switched to abraxane plus bevacizumab ( table 1 ) . in july 2008 , after two rounds of chemotherapy with the new agents , her ctc level had again dropped to 0 . repeat pet / ct imaging at the end of july confirmed a pr to therapy . over the summer , the patient experienced significant bevacizumab toxicity . based on the positive response observed with imaging and ctc levels , the decision was made to discontinue treatment with the bevacizumab component of her treatment regimen . her ctc level remained at 0 upon repeat measurement in september 2008 . based on pr on imaging and negative ctc counts , in september the decision was made to discontinue all chemotherapy due to progressive toxicity experienced by the patient , including new onset neuropathy ( table 1 ) . assessment of tumor activity in this case was difficult using conventional tumor markers and pet / ct imaging due to a lack of concordance between these assessments , which ordinarily would diminish confidence in treatment decisions . the use of ctc enumeration information to support clinical decision making in a setting of conflicting assessments has been suggested previously . the specificity and responsiveness of the serum tumor markers , cea and ca 27.29 , are reported to be fairly low . radiographic assessment may have interreader variability and may not reflect changes in disease status in a timely manner . ctc concentration has been reported to be specific for cancer and to respond to changes in disease state promptly [ 11 , 12 ] and so may compliment other assessments . after the initiation of fulvestrant plus pamidronic acid therapy in november 2006 , the patient 's ctc count rose to 6/7.5 ml , then stabilized . although the ctc count had risen , imaging studies showed response to treatment and the patient 's performance status was good , so therapy was continued . by december 2007 , the ctc count had reached 0 , which brought it into agreement with the pet / ct imaging studies . based on the imaging studies in july and december showing response to therapy and the absence of ctcs , the decision was made to continue therapy with fulvestrant and pamidronic acid . in this example , ctcs may have been more reflective of disease state than the serum tumor markers . at the may 2008 visit , both ctc and ca 27.29 levels the decision was made to start a new line of therapy with abraxane plus bevacizumab . the patient responded to this change in therapy as assessed by ctc concentration in july 2008 , which decreased to 0 . although ctc count often responds to changes in disease state fairly quickly , in some instances , changes may not be seen in the first measurement [ unpubl . , the ctc count increased in the first half of 2007 following initiation of fulvestrant plus zoledronic acid therapy , while imaging suggested a pr . the ctc count stabilized at 6/7.5 ml from the july and october measurements , then decreased by the third measurement in december 2007 . in our experience , ctc count responses following hormonal therapy in breast cancer may require 34 months or more to show a significant change . in contrast , the decrease in ctc concentration observed in the first measurement following change in therapy to abraxane plus bevacizumab in july 2008 closely tracked the pr determined by imaging , which is typical in our experience for response of ctc counts to chemotherapy . despite the differences in time to response , in both of these examples from this case the ctc count was ultimately concordant with imaging . the specificity of ctcs for breast cancer   was important in considering the use of ctc enumeration information in this case . the patient experienced adverse effects attributed to bevacizumab   in the summer of 2008 , and the decision to discontinue bevacizumab was supported by the favorable imaging results and negative ctc levels following the change in therapy . subsequent negative tests for ctcs in july 2008 and september 2008 gave us additional confidence that a discontinuation of paclitaxel therapy could be allowed so that the patient could recover from its adverse effects , using ctc tests as an option to monitor for disease progression . the use of ctc information in this context is consistent with recommendations to limit the use of imaging to monitor for cancer recurrence . in addition , the type of therapy may influence the time to see a ctc response in breast cancer , with hormonal therapy often taking longer than chemotherapy . finally , in this instance , we found ctc measurement a useful adjunct to imaging for monitoring for disease recurrence to give the patient a needed drug holiday .
management of metastatic breast cancer is critical to maximizing survival with good quality of life . 
 circulating tumor cell ( ctc ) levels in the peripheral blood hold promise for enabling improved patient care . 
 we describe a case of a 47-year - old female with infiltrating ductal carcinoma who developed metastatic disease . 
 serum tumor markers were discordant with imaging studies at several time points . 
 ctc levels were used to support decision making in light of the discordant data . 
 the use of this tool enabled prompt changes in therapy with progressive disease and supported suspending therapy to enable recovery from treatment adverse effects when a significant response was detected by imaging and ctcs were absent from the peripheral circulation . 
 the additional information provided by ctc enumeration helped clarify disease status and provided support for treatment decisions .