Focal Radiation Enhances Paclitaxel Therapy In A Mouse Model Of Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) accounts for 15-20% of all breast cancers in the US. In general, patients have poorer prognosis and therapeutic intervention is more challenging due to insensitivity to hormonal and anti-HER2 therapies. Therapeutic options include chemotherapy and/or radiation (RT) treatment. In this work we utilized HCC70, a human TNBC cell line, grown subcutaneously in NSG mice. We investigated whether the combination of focal RT and paclitaxel would improve anti-tumor activity over paclitaxel alone. RT therapy has typically been delivered in low doses over long periods of time. More recently higher fractions of RT are being given in shorter time intervals. Utilizing the Small Animal Radiation Research Platform (SARRP; Xstrahl, Suwanee, GA) we compared a low dose (2.5Gy) fractionated regimen to a higher dose but less frequent regimen (8Gy, QDx3) either as monotherapy or in combination with paclitaxel (15mg/kg weekly). The total cumulative dose of radiation was 24-25Gy in both radiation regimens. Paclitaxel alone produced moderate activity with a 10 day tumor growth delay and no tumor regressions. Treatment with low dose RT resulted in tumor stasis for ≥68 days, but there were no tumor regressions or tumor free survivors (TFS). Treatment with 8Gy, produced a 75% incidence of confirmed partial regressions (PR) and a 25% incidence of complete regressions (CR) with no TFS. In this group we observed slightly more body weight loss (BWL), more frequent clinical signs, and more frequent need for food and water supplementation than with the fractionated RT regimen. Mean BWL was ~10% with a nadir around 8-10 days post first RT dose. BWL was recovered over the next 1-2 week period. The combination of low dose focal RT with paclitaxel produced activity similar to that with high dose radiation (50% PR, 40% CR, and 1 TFS). Treatment with paclitaxel plus 8Gy RT was highly efficacious, producing an 80% incidence of CRs, all of which remained tumor free at study day 108. The remaining mouse experienced tumor stasis in excess of 63 days. Thus, a higher dose of focal RT given in shorter intervals in combination with systemic paclitaxel resulted in the most efficacious therapeutic strategy but at the cost of increased BWL and clinical signs. Citation Format: Maryland Franklin, Thomas Dailey, Wilbur Leopold. Focal radiation enhances paclitaxel therapy in a mouse model of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5194. doi:10.1158/1538-7445.AM2017-5194