Projection Description
This year alone, approximately 11,000 women will be diagnosed with Stage IV (metastatic) breast cancer. The median survival for these women is 2 to 3 years, with only 27% surviving to 5 years. Despite recent innovations including type and order of treatment, drug delivery methods and availability of targeted therapies, the ability to make the best choice for the patient who has already been treated with multiple regimens remains an extreme clinical challenge.

This decision is often empiric, based upon the treating physician's experience and their own personal bias of how the patient may tolerate the therapy, rather than based on scientific evidence. Unfortunately, as patients are treated with multiple chemo therapies the likelihood they will be resistant to current and future treatments increases. There is an urgent need for enhanced tools to guide and enable physicians to make more effective clinical decisions. In particular, physicians need rationalized measures to predict the probability of a patient's response to therapy much sooner than what current imaging scans and standard blood work can provide. We and others believe that this can be accomplished by measuring the genetic and molecular information from breast cancer cells that are circulating in the blood-stream of Stage IV breast cancer patients. These cancerous cells in the blood stream are called „Circulating Tumor Cells' (CTCs).

CTCs enter the blood stream when they break away from the primary breast tumor. They have the capability of surviving in the patient's bloodstream or bone marrow, avoiding detection by the immune system, and ultimately travel to distant organs or sites in the body (such as lung, bone, and brain) where they then exit the bloodstream and form a secondary tumor. This secondary tumor mass, commonly known as a metastatic tumor, kills the majority of Stage IV patients. Importantly, the CTCs are representative of the metastatic tumor mass and they can be extracted from the blood for examination. Technological advancements enabled by “Genomics” can identify information about cancer cells (including CTCs) that can empower oncologists to make the optimal therapeutic decision for each patient as they undergo active treatment. This project is a proof of principal or feasibility study that, if successful, would guide future development of a Phase I clinical trial.

The objective of this project is to isolate CTCs from the blood of Stage IV patients at regular intervals during treatment, and profile the DNA of these CTCs. Our goal is to determine whether this information can provide physicians with additional scientific evidence that may predict a more effective treatment plan for the patient. This approach has been shown in TGen-initiated studies to be effective when profiling the genetic information in tumor biopsies from advanced tumors. Importantly, advanced tumors often form in regions that are difficult, if not impossible to biopsy. This study avoids this problem by isolating advanced cancerous cells from a routine blood draw, which is an efficient and very low risk procedure for the patient.

CTCs are extremely rare cells surrounded by billions of normal red and white cells in the bloodstream. Due to the rarity of CTCs, enrichment steps are necessary to increase our ability to measure DNA alterations in cancerous CTCs, while avoiding the normal blood cells. Moreover, a minimal number of CTCs are required in order to obtain enough genetic information to successfully perform our analysis. We have recently determined the minimal number of CTCs that need to be extracted from a patient's blood to allow us to make accurate measurements of the tumor DNA using advanced genomic technologies. We have also optimized a way to make reliable copies of the DNA from isolated CTCs. This step is essential as it significantly amplifies our ability to identify the genetic alterations. These alterations are the link to deciding which drug will be optimal for each individual patient's tumor. This approach is a cutting-edge example of precision medicine. This study is currently focused on enhancing procedures for isolating as many CTCs as possible from an individual blood sample. This process involves a novel method to recognize and separate the cancer cells from the normal blood cells.

We are currently meeting our budget projections based on workflow timelines.

We will continue to optimize the procedure for isolating the highest number of CTCs as possible from blood samples. Thus far, our breast cancer cell recovery rate from blood is approximately 70%, which is equivalent to industry standards. The final phase of the project will apply the CTC isolation technology to blood donated by Stage IV breast cancer patients. We plan to enroll approximately 25 patients who have measurable CTCs in their blood to determine the accuracy of our methodology.

1) Optimization of the minimal number of CTCs required to perform high resolution DNA profiling has been successfully completed. 2) A method to extract CTCs from patient blood has been successfully developed. 2) Institutional Review Board (IRB) approval of a protocol to consent stage IV breast cancer patients to donate blood: We anticipate approval by mid January 2012. 3) Perform isolation of CTCs from the blood of 25 stage IV patients: We anticipate consenting 1-2 cases per week, thus blood collection will be completed approximately by May 2012. 4) Examine the DNA profile of patient CTCs at high resolution. Determine whether this information provides a rationale for optimal therapeutic strategies that would not have otherwise been selected. Profiling will be completed within 1 month of collection of all patient CTCs.