A Window Into the Future of Cancer Monitoring

Maurie Markman, MD


April 24, 2013

Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer

Dawson SJ, Tsui DW, Murtaza M, et al
N Engl J Med. 2013;368:1199-1209


In an effort to determine whether it might be possible to improve upon current methods to monitor the course of metastatic breast cancer in patients treated with antineoplastic therapy, investigators developed personalized assays that could measure circulating cell-free tumor DNA using somatic mutations specific to each individual patient. Within the overall cohort of 30 patients, investigators were successfully able to identify and assess individualized tumor DNA biomarkers in 97% of patients (29 of 30), along with CA 15-3 tumor antigen in 78% of patients and circulating tumor cells in 87% of patients. Changes in the level of cell-free tumor DNA were found to be an earlier indicator of response to antineoplastic therapy and showed a superior correlation with the overall tumor burden vs the other 2 parameters evaluated.


Although this is only a preliminary report of a small group of patients and requires confirmation by others, this study provides a provocative view of the future of cancer monitoring.

For several reasons, there has been considerable interest among both researchers and clinical oncologists in a potential role for some form of a circulating tumor DNA marker. First, as suggested in this small series in the management of metastatic breast cancer, it has been hoped that such testing would be more sensitive as a marker of overall tumor burden rather than simply indicating the presence of the cancer.

Second, there is a desire to establish indication of an earlier response to treatment compared with currently employed methodology, such as radiographic imaging demonstrating a decrease in the size of a measurable mass, or a decrease in the level of a nonspecific tumor marker such as CA 15-3. This type of information would be quite useful in the decision to continue a particular antineoplastic strategy despite the development of side effects and could help to justify the costs associated with a regimen.

Third, in the absence of a response (or evidence of progression), alternative strategies could be implemented earlier, avoiding both the toxicities and costs associated with continuing an ineffective program.

Finally, and perhaps most important, a particularly attractive feature of circulating tumor DNA would be the opportunity to examine changes in the somatic genomic profile of the tumor itself, which might provide vitally important molecular information related to the mechanism of tumor resistance within that individual cancer.

With our increasing understanding of the mechanisms of resistance, the genetic events that underlie the success of tumors to escape the inhibitory effects of targeted drugs, and the availability of novel agents designed to effectively affect particular molecular targets, knowledge of the unique mechanism in an individual tumor type is essential to the development of the most rational strategy to overcome developing resistance. Rebiopsying a solid tumor is often difficult (if not impossible in many settings), potentially quite risky, and certainly expensive, particularly if it is to be done on several occasions. However, an ability to find unique patterns of circulating tumor-specific DNA related to specific mutations may provide critical assistance in future disease management.

The current report offers a potential window into this issue, which will hopefully be a focus of future research.