Identifying treatment options for triple negative breast cancer patients using RNA-sequencing.

31 Background: In the context of diagnostics, RNA is proxy for proteins and proteins are typically targets for drugs; e.g. breast cancer is typically driven by over-expression of various hormone receptors and Her2. In the current standard-of-care setting there is no measurement of mutations. Furthermore, all the markers for response to the new immune therapies are expressed as mRNA. Approximately 15% of the breast cancer patients are triple negative. Due to the poor outcome of chemo, standard-of-care guidelines (NCCN) suggests doctors encourage the patient to enroll in clinical trials. However, with more than 2000 ongoing trials in breast, which trial could potentially benefit the patient? Methods: Using the RNA-seq data from the TCGA study, we analyzed more than 120 triple negative datasets. Results: We found at least one over-expressed checkpoint inhibitor target in almost all the patients, suggesting that if you analyzed for all of the checkpoint targets, it would be possible to find a clinical study for these patients. Furthermore, when we analyzed over-expressed tumor antigens, we realized that it would be possible to design sophisticated combination trials with this information. In addition, we identified patients that were BRCAwt with an impaired DNA repair pathway; e.g. some had BRCA silencing and could potentially benefit from PARP inhibitors. Finally, a small number of patients overexpressed the androgen receptor for which there is a drug approved for prostate cancer. Conclusions: Compared to DNA analysis, tumor RNA profiling has the potential to guide a much broader set of drugs and treatment approaches including immunotherapy and chemotherapy. Messenger RNA (mRNA) analysis can reveal tumor antigens and drug targets expressed by cancer cells, as well as the vital status of the tumor microenvironment including immune response, the integrity of DNA repair mechanisms, and the engagement of angiogenesis and other cancer-related pathways.