Grant: Project Grant

Ductal carcinoma in situ (DCIS) is a non-invasive type of breast cancer. Treatment of DCIS is recommended as some DCIS tumors can develop into invasive breast cancer. Most women are treated with breast-conserving surgery followed by breast radiation (RT) which is shown to lower the risk of developing recurrent disease (DCIS or invasive) in the same breast, called Local Recurrence (LR). We are currently unable to identity which women will benefit from RT (ie RT will prevent the LR) from those that will derive no benefit because they develop a LR despite receiving RT. Genomic biomarkers that predict radiation benefit do not exist. With prior funding from CIHR, we worked extensively to meet the challenges of sequencing ~400 DCIS tumors, and discovered a novel genomic biomarker that predicts RT benefit. We call the new assay the Radiation Benefit Score (RBS). The RBS contains 100 genes that predicts RT benefit in individuals diagnosed with DCIS. We found that DCIS tumors with a low RBS had no benefit from RT (i.e. LR developed despite receiving RT) whereas those with a high RBS score had a significant benefit from RT with almost no LRs. In the proposed study, we plan to build on this work by evaluating the RBS assay in an additional 3300 individuals with a DCIS diagnosis in a platform that is suitable for clinical translation (nCounter NanoString Inc). We will first evaluate the RBS in 900 individuals to refine and finalize the RBS assay and then test the final RBS assay in another 1658 cases (external validation). Performing these essential two steps will optimize the timeliness and cost efficiency and will substantially increase the success of discovering a novel assay that will have clinical utility. This will enable clinicians to accurately predict in which individuals RT will reduce the risk LR from those that will not benefit from RT who can be spared side effects of RT and be recommended alternate treatments to lower the risk of LR, especially invasive cancer.