Dynamic Response of Disseminated Tumor Cells and Circulating Tumor Markers to Targeted Adjuvant Therapy
Technical Report,30 Sep 2017,29 Sep 2018
The Trustees of the University of Pennsylvania Philadelphia United States
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A significant proportion of patients who receive adjuvant therapy for breast cancer recur, usually with distant metastatic disease. Since recurrent breast cancer is typically incurable, the propensity of breast cancers to recur following treatment is the most important determinant of clinical outcome. Breast cancer recurrences arise from the pool of local and disseminated residual tumor cells DTCs that survive in their host in a presumed dormant state following treatment of the primary breast cancer. Consistent with this, DTCs present in the bone marrow, and circulating tumor cells CTCs present in the bloodstream, after treatment are strongly associated with an increased risk of recurrence. At present, however, the underlying biology that enables residual tumor cells to remain dormant, often for years, evade therapy and ultimately recur is poorly understood. Moreover, the molecular properties of DTCs and CTCs, as well as their biological relationship and comparative utility for evaluating risk and response to therapy are as yet undefined. This lack of understanding, along with the lack of therapeutic approaches specifically targeting these cells as a means to prevent recurrence, constitute major obstacles to the successful treatment of breast cancer patients. Our findings to date advance new approaches for detecting and characterizing minimal residual disease.
- Medicine and Medical Research