Abstract P2-11-11: Clinical utility of a radiosensitivity molecular signature: Identification of breast cancer patients that benefit from RT boost dose

Abstract

Abstract Objective: In previous studies we developed a radiosensitivity molecular signature (RSI) that has been independently validated in multiple disease sites (n = 652) including breast cancer 1-3. Here, we test whether RSI can be utilized to identify sub-populations in breast cancer that benefit from RT dose intensification (boost). Methods: RSI was tested in two published breast cancer datasets (n = 342) 4. Patients were selected if they had experienced a local recurrence within the first 10 years after primary treatment or were free of local recurrence for a minimum of 10 years after treatment. Primary treatment was initial breast-conserving surgery plus whole breast RT with/without a boost (no boost, n = 94, low boost < = 66 Gy, n = 148, high boost >66 Gy, n = 100). Patients were treated between January 1984 and November 2002. RSI was generated as previously described 1-3. Time to local recurrence was used as the endpoint for the study. Results: Increased RT dose (>66 Gy vs. < = 66 Gy) resulted in a slight decrease in local recurrence risk that did not reach statistical significance (p = 0.11). As hypothesized, RSI-high patients (more radioresistant) were sensitive to increased RT dose (high RT-boost) which resulted in a decrease in local recurrence (HR = 0.3418, CI 0.1195-0.9777, p = 0.036). In contrast, RSI-low and intermediate patients had similar local recurrence risk independent of RT dose (RSI-low HR = 0.7687, CI 0.3404-1.736, p = 0.53, RSI-intermediate, HR = 0.9115, CI 0.5125-1.621, p = 0.75). Importantly, there were no statistical differences in the distribution of known prognostic variables between RSI-determined sub-populations (RSI-low, intermediate, high) including age, T-stage, margin status, nodal status, adjuvant chemotherapy, hormonal therapy, grade and molecular subtype. Conclusions: RSI identifies a sub-population of breast cancer patients that benefit from increased RT-dose. RSI may be utilized to support RT-based decisions (high boost vs. low boost vs. no boost) in breast cancer. 1. Eschrich S, Fulp WJ, Pawitan Y, et al: Validation of a Radiosensitivity Molecular Signature in Breast Cancer. Clin Cancer Res, 2012 2. Eschrich S, Zhang H, Zhao H, et al: Systems biology modeling of the radiation sensitivity network: a biomarker discovery platform. Int J Radiat Oncol Biol Phys 75:497-505, 2009 3. Eschrich SA, Pramana J, Zhang H, et al: A gene expression model of intrinsic tumor radiosensitivity: prediction of response and prognosis after chemoradiation. Int J Radiat Oncol Biol Phys 75:489-96, 2009 4. Servant N, Bollet MA, Halfwerk H, et al: Search for a gene expression signature of breast cancer local recurrence in young women. Clin Cancer Res 18:1704-15, 2012. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-11.