The ultimate goal of all CBCP research projects is to generate new knowledge that will benefit breast cancer patient treatment. The large volume of molecular data from CBCP patients, integrated with the clinicopathologic data including the highly valuable treatment and outcome information, provides a gold data mining opportunity for CBCP scientists to generate new hypotheses for study and validate new experimental findings. This opportunity is even more enriched by the availability of large-scale high-quality datasets such as those from TCGA across multiple cancer types. Such raw data, combined with public annotation databases on genes, proteins, pathways, and human diseases, will enable derivation of new knowledge for breast cancer patient treatment.

The project is centered around two human use clinical trials/protocols:

1. Tissue and Blood Library establishment for Molecular, Biochemical and Histologic Study of Breast Disease
2. Creation of a Blood Library for the Analysis of Blood for Molecular Changes Associated with Breast Disease and Breast Cancer Development

Objectives for the above human use clinical trials are:

1. Acquisition and banking of breast tissue, lymph nodes, and/or blood from informed and consenting donors
2. Experimental analysis of DNA, RNA and/or proteins isolated from donor tissues for molecular, biochemical, and/or histopathological analysis
3. Establishment of an integrated and relational database for tissue/serum and patient clinical characteristics that will provide the resources necessary to achieve the following future goals
4. Establishing a repository of high quality breast tissue and related (lymph nodal, blood) specimens for research on breast cancer and associated breast diseases
5. Permitting the establishment of a single relational database with accurate and comprehensive biologically and clinically relevant information on breast diseases.

** If interested in Breast Cancer Research or enrolling in a study, please contact our Senior Research Protocol Coordinator at sara.d.sakura.ctr@mail.mil or 301-295-8556.**

There are two themes for CBCP research. Theme 1 focuses on breast cancer mechanistic studies of clinically important questions, and Theme 2 focuses on therapy-relevant molecular studies of breast cancers.

For Theme 1 studies, one important topic is integrative profiling of breast cancers. The current 4 major breast cancer subtypes—termed “intrinsic subtypes”—were based on gene expression profiling. IHC-based subtyping using ER, PR, Ki67 and HER2 are available and are of clinical significance, although such subtyping is sometimes referred to as surrogate for intrinsic subtyping. Information on a broader panel of proteins and their post-translational modifications as well as their subcellular location information is needed for a more comprehensive understanding of breast cancer stratification which is important for cancer treatment. Thus such studies are important not only for Theme 1 but also for Theme 2, for example, the identification of protein markers for endocrine resistance.

For Theme 1 studies, the CBCP provides a good research environment on young breast cancer patients and African American patients. Young age at breast cancer diagnosis and being African American are considered risk factors for poor outcomes of breast cancer patients. CBCP has enrolled a high percentage of AA patients, and there is also a good size of young breast cancer patients enrolled due to the demographics of the active-duty military population. Using these resources CBCP scientists have conducted molecular studies, and have proposed additional molecular, epidemiologic, and comparative survival analysis using both CBCP data and the data in the public domain.

The topic of tumor heterogeneity is not only important to the understanding of breast cancer development (Theme 1), but also of therapeutic significance (Theme 2). Tumor heterogeneity refers to the cellular heterogeneity of tumor development environment, where there are cancer cells, stromal cells, lymphocytes, etc., and the Murtha Cancer Center has chosen “Inflammation, Infection, Immunity, and Stroma (I3S) as one of the focuses for research. Tumor heterogeneity also refers to the fact that one physical tumor could contain multiple lineages of tumors that are not necessarily of the same molecular subtype. When only one subtype was diagnosed and treated, the other subtypes could be left untreated which could lead to detrimental outcome of the patient.

Additional topics are proposed to be studied on mechanistic understanding of breast cancer development. These include genetic dispositions, exposure to environmental risks, access to healthcare and treatment disparities, and impact of certain life style factors as well as comorbidities.

For Theme 2 studies, profiling of human biospecimens alone is important but insufficient; biospecimens are no longer alive after excision from the human body, and in order to study the impact of drugs or the response to drugs of a mutated gene, a live model system is needed. CBCP scientists has developed tissue culture systems for both 2D and 3D model systems of breast cancer cell lines, with a focus on the triple-negative subtype that are currently difficult to treat. Findings from such studies are validated or sometimes guided by bioinformatics analysis of the data on human tissues.