Grant: Project Grant

Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer but some DCIS will progress to invasive breast cancer. DCIS is not life-threatening but women with DCIS require treatment to lower their risk of developing invasive breast cancer. Most women with DCIS receive breast-conserving surgery and whole breast radiation treatment (RT) which is proven to lower the risk of recurrent disease including invasive breast cancer. Our inability to identify which women benefit from radiation results in unnecessary treatment of many women who will not benefit from radiation and inadequate treatment of women with aggressive but radiation-resistant DCIS who will develop recurrence despite receiving radiation. Genomic biomarkers that predict chemotherapy benefit have revolutionized the treatment of breast cancer, but predictors of radiation benefit are unknown. The goal of this study is to develop a biomarker assay that predicts RT benefit in DCIS. This will help reduce unnecessary RT in women who have a low risk of recurrence. However, it will also identify those with aggressive DCIS who will respond (benefit) from radiation and identify those who have radiation-resistant disease in whom alternate interventions are needed to lower their future risk of breast cancer. To accomplish this goal we have established 3 cohorts of DCIS. The Sunnybrook institutional cohort will be used for genomic profiling and assay (termed DCIS RT assay) development. The Ontario population-based DCIS cohort and the Swedish DCIS clinical trial cohort will be used as two independent cohorts for validation of the novel assay. We will also create a nomogram which will help provide women with more accurate estimates of the risks/benefits of RT. We have assembled an international team of experts with a proven track record who have the expertise to accomplish this goal and improvement the management of DCIS by reducing over-treatment and reducing the future burden of invasive cancer worldwide.