Abstract P1-15-12: Single Nucleotide Polymorphism (SNP) Bayesian networks (BNs) Predict Risk of Chemotherapy-Induced Side Effects in Patients with Breast Cancer Receiving Dose Dense (DD) Doxorubicin/Cyclophosphamide Plus Paclitaxel (AC+T)

Background: Despite advances in supportive care, patients undergoing standard chemotherapy for breast cancer are at significant, but unequal, risk for the development of treatment-induced side effects. Current methods for predicting risk are inconsistent and unreliable. Because the pathobiology of many side effects is regulated by the synergistic interaction of simultaneously expressed genes, we reasoned that a novel approach to risk prediction could be achieved by the development of clusters of SNPs defined by BNs. The present study was designed to assess the feasibility of identifying BNs that were associated with regimen-related diarrhea, oral mucositis, nausea and vomiting, fatigue, cognitive dysfunction, and neuropathy in patients with breast cancer treated with dose-dense AC+T. The primary end point was an area under the receiver operating characteristic curve (aROC) >0.80. Methods: After informed consent, 78 patients with breast cancer who had received at least 3 cycles of (DD) AC+T were enrolled and saliva samples were collected. Salivary DNA was isolated and analyzed on Illumina Omni microarrays (2.5x10 6 SNPs). Standard supportive therapy for prevention and management of side effects was provided. The frequency and severity of diarrhea, oral mucositis, fatigue, cognitive dysfunction, neuropathy, and nausea and vomiting were determined using Patient Care Monitor © , a validated patient-reported symptom assessment instrument. BNs were developed for each of the 6 side effects using Bayesian methods including 10-fold internal cross-validation. Results: The incidence of clinically significant side effects was higher than anticipated by the literature and is reported in Table 1 along with the accuracy and aROC. Conclusions: We identified SNP-BNs associated with moderate to severe common side effects of AC+T regimens used to treat breast cancer. These BNs, sourced from salivary SNPs, should provide clinicians with accurate actionable information that predicts side effect risk for patients who are scheduled to receive DD AC+T for the treatment of breast cancer. • Despite current supportive care options, the risk of side effects among patients with breast cancer receiving the most common forms of therapy, including chemotherapy, is significant. • There is no current precise method to predict risk of side effects clinically. Consequently, providers and patients are limited to using commercially available agents for those side effects identified by clinical criteria as high risk; whereas, other side effects are dealt with on a manage-as-they-emerge basis. The ability to understand risk prospectively has the potential to modify choices relative to treatment regimens and aggressiveness of care. • The biological basis of many side effects is continuing to be described, but it is clear that genetics plays a significant role in determining individual patient risk. • It seems most likely that the genetic impact on risk is a result of ‘teams’ of genes functioning