Abstract P1-13-04: Efficacy of adjuvant 5-Fluorouracil in residual HER2-negative breast cancer following neoadjuvant chemotherapy

Abstract

Abstract Background: Patients with residual disease following neoadjuvant chemotherapy have an increased risk of relapse. Recently the CREATE-X trial demonstrated that adjuvant capecitabine (oral prodrug of 5'deoxy-5-fluorouridine), prolonged disease-free survival and overall survival among patients with HER2-negative breast cancer who had residual invasive disease after neoadjuvant chemotherapy containing anthracycline, taxane, or both. Therefore, we sought to evaluate the antitumor efficacy of 5-fluorouracil (5-FU) in patient-derived xenografts (PDXs) from residual tumors resistant to neoadjuvant chemotherapy. Methods: Antitumor efficacy of 5-FU was assessed in vivo in three PDXs varying in hormone receptor status (0, 4% and 11% respectively), generated from residual tumors of primary breast cancer patients treated with neoadjuvant chemotherapy containing anthracycline, and taxanes. In addition, significance of timing of therapy was also assessed, comparing efficacy of initiating treatment upon implantation (immediate start cohort; mimicking treating residual disease with adjuvant therapy), with initiating treatment upon establishment of PDX (standard start cohort). Results: 5-FU was efficacious in established PDX models that are triple negative (0% ER; p< 0.0001), low ER positive (4% ER, p=0.0213) and ER-positive (11% ER; p= 0.0390), decreasing growth compared to the cohort. However, there was no statistically significant difference between the immediate start cohort and standard start cohort. Western blot analysis of the treatment-naïve derived mouse tumors recognized RB as a predictive biomarker for 5-FU response. Conclusion: 5-FU has anti-tumor activity in residual HER2-negative PDX models resistant to taxanes, and anthracyclines in the neoadjuvant setting. Citation Format: Owusu-Brackett N, Scott S, Yuca E, Evans KW, Tapia C, Meric-Bernstam F. Efficacy of adjuvant 5-Fluorouracil in residual HER2-negative breast cancer following neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-13-04.