Study
PLCO
(Learn more about this study)
Project ID
2014-0002
Initial CDAS Request Approval
Apr 4, 2014
Title
A Simple System for the Early Detection of Breast Cancer
Summary
A diagnostic for early detection of breast cancer could be important in the eradication of the disease. Ideally such a diagnostic would be simple, inexpensive and highly specific. We believe that the immunosignature diagnostic technology may be able to fulfill these specifications. We propose to use the PLCO breast cancer sera samples to test this. Immunosignatures are generated by applying diluted blood samples to peptide arrays. The peptides (350,000) are designed to evenly represent non-natural sequence space. The same array is used for diagnosis of any condition. Essentially only antibodies bind to the array and on detection with secondary antibodies reveal a pattern of binding that correlates with health status. The arrays are manufactured using the photolithography system used in the electronics industry making them amenable to scaling up in volume and down in cost. We have demonstrated that immunosignatures can distinguish sera from people diagnosed with a particular disease from non-disease individuals for over 30 different conditions, including breast cancer. From mouse transgenic models it is clear that the signature of early mammary cancer is distinct from late disease. Therefore we propose to use the samples taken in the PLCO study before diagnosis to determine if an early immunosignature of breast cancer can be distinguished and if so how early. A training and test set of samples will be sequentially analyzed starting at year 0-1 and proceeding back in collection time, one year at a time, until a diagnosis cannot be made. We have the following specific aims: 1) Can an early immunosignature diagnostic be established and if so how early, 2) What is the correspondence between stage at diagnosis and receptor type with immunosignatures and 3) Does real time before diagnosis correspond to “tumor time” and 4) Is there more diversity in signatures early than late in progression.
Aims
We propose that the immunosignatures of individual breast tumors may have high diversity early and then coalesce as the tumors mature. Therefore, the characterization of the signatures should be done by characterizing signatures going back in time from the point of initial diagnosis. Our aims will be: 1. Determine the immunosignature of case versus controls in a training set then evaluate in test set, doing so for each one year cohort of less than 1yr, 1-2yr, 2-3yr and 3-4yr before diagnosis. 2. Determine if there is a stratification in the signatures relative to stage or receptor status at diagnosis. 3. Determine to what extent tumor signatures group in real time or not. 4. Determine if the hypothesis of increased heterogeneity in early signatures is correct.
Collaborators
