Triple negative breast cancers (TNBC), comprise 15-20% of breast cancers, and are associated with later stage at diagnosis, increased mortality, and occur more frequently in younger women where mammographic screening is less reliable. TNBCs are more likely to be diagnosed by physical exam than by mammographic screening. There is an unmet clinical need for biomarkers for the early detection of TNBC. Here, we are proposing the development of a plasma-based biomarker panel for the routine screening of women over the age of 40 for TNBC that can be used to identify women for further imaging.
The overall study design involves the identification of three distinct types of blood-based biomarkers:
1. Autoantibodies (Anderson/LaBaer) 2. Protein antigens (Li/Lampe; Zangar). 3. miRNA
(Huebner/Croce). These biomarkers will be validated in a step-wise fashion using samples provided by the CEVCs and multi-institutional cohorts, with study design and evaluation by the DMCC.
Aim 1. Verification of novel biomarkers for TNBC
Aim 2. Validate the top biomarkers for TNBC using a diagnostic set of plasma.
Aim 3. Determine the sensitivity, specificity, and positive predictive value of the top marker
combinations found in aim 2 to distinguish TNBC from benign breast disease, and for the detection of ER+ and Her2+ breast cancer, using the EDRN Reference Set.
Aim 4. Develop a phase III validation plan for testing the top biomarkers and biomarker combination for TNBC detection using prediagnostic sera from WHI, ROCA, and PLCO.
We will systematically compare existing TNBC biomarkers that have been identified from multiple laboratories, targeting protein antigens, autoantibodies, and miRNAs. These biomarkers will be validated in a step-wise fashion using samples provided by the CEVCs and multi institutional cohorts, with study design and evaluation by the DMCC. The individual and composite sensitivities and specificities of these biomarkers for the detection of TNBC and non-TNBC breast cancers will be evaluated. These studies will lead to the development of a phase III validation plan for testing the top biomarkers and biomarker combination for TNBC detection using prediagnostic sera from WHI, ROCA, and PLCO.