EDRN Breast and Ovary Cancer CVC, Study 1: Preliminary validation of breast cancer early detection biomarker candidates from our WHI discovery project
No involved investigator sites defined.
There is an urgent need for breast cancer early detection biomarkers given that none are currently available and given the considerable public health importance of breast cancer. An estimated 192,370 women were diagnosed with breast cancer in the United States in 2009, accounting for 27% of all cancers diagnosed among U.S. women. With respect to mortality, 40,170 women will die of breast cancer in 2009, accounting for 15% of all cancer related deaths among U.S. women. Breast cancer mortality rates have declined over the past decade in the U.S. primarily as a result of the implementation of population-based screening programs and advances in breast cancer treatment. Despite these changes, breast cancer is still associated with significant morbidity (recurrence, anxiety, and treatment side effects) and mortality. Continued improvements in our ability to detect breast cancer early offer the promise of further reducing the burden of this disease, as breast cancer detected at an earlier stage is much more curable than is metastatic disease. The current 5-year survival rate for localized breast cancer in the U.S. is 98%, but is only 27% for metastatic disease. We recently completed a unique large scale study aimed at discovering breast cancer early detection biomarkers. Our validation of EGFR as a potential breast cancer early detection biomarker in the described preliminary Phase 3 validation study provides important evidence that there may indeed be breast cancer early detection biomarkers detectable in plasma, that our discovery platforms were able to identify viable candidates, and that more comprehensive validation of our discovered candidates, especially those much higher ranked, in a follow-up study is warranted. Our overall goal is to reduce suffering and death due to breast cancer by validating plasma biomarkers that can be used to detect breast cancer early, when it is most treatable, by completing the following aims: 1. Conduct a second screen of the most promising breast cancer early detection biomarkers to identify the candidates most suitable for validation: We have identified a lengthy list of promising biomarkers, however, due to the inherent false discovery rate of this work, this list needs to be culled. 2. Validate the top 50 novel early detection biomarkers in an independent sample for breast cancer overall and for several breast cancer subtypes: We will validate the 50 most promising biomarkers identified following Aim #1 in a sample of women completely independent from those used for biomarker discovery using a multi-tiered approach. This includes validating markers in two independent sets, and evaluating them within the same individuals using plasma from two time points. Of these 50 promising biomarkers we expect that only a few will indeed be validated, or that a panel of the top markers will be required to reach useful sensitivity and specificity. However, as there are currently no available biomarkers for breast cancer, even the identification of one would be an important discovery. For each specific aim we will consider both breast cancer as a whole and clinically relevant subtypes of breast cancer based on histology and tumor marker expression. Analyses will also be conducted that consider various patient characteristics that are known or suspected to influence the plasma proteome, such as use of menopausal hormone therapy. Given the biological heterogeneity of breast cancer, we expect that there will be markers unique to different clinically and molecularly defined breast cancer subtypes.
There are currently no biomarkers annotated for this protocol.
No datasets are currently associated with this protocol.