Abstract

Introduction: Patients with locally advanced, triple-negative breast cancer (TNBC) typically receive neoadjuvant systemic therapy (NAST). However, the response of TNBC to NAST is varied and a prognostic marker is still lacking. Since angiogenesis plays an important role in cancer progression, the quantification of changes in the tumor vasculature during treatment has the potential to provide useful information for characterizing the treatment response. We have recently developed a method to quantify changes in tumor-associated vasculature through a novel analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). In this study, we investigated its ability to monitor the response of TNBC to NAST. Methods: Dynamic contrast-enhanced (DCE) MRI was acquired in TNBC patients (N = 50; 25 pathological complete response (pCR), 25 non-pCR) before, after 2 and 4 cycles of Adriamycin/Cyclophosphamide (A/C), as part of the ARTEMIS trial (NCT02276433). Using DCE-MRI, we identified the tumor-associated vessels via a breast vasculature analysis. Specifically, the difference between pre- and post-contrast DCE-MRI images was enhanced by a histogram-based intensity transfer function. The 3D vasculature in the breast was then segmented by applying a Hessian filter. Given the vasculature segmented by the algorithms and the tumor masks segmented by radiologists, a lowest-cost tracking algorithm was used to automatically detect the vessels that are most likely to contact the tumor. These vessels are defined as tumor-associated vessels (TAV). The number of TAVs per patient was tabulated and the Wilcoxon rank sum test compared the TAV values before (V1), after 2 cycles (V2), and after 4 cycles of NAST (V3). Additionally, we compared the percent change of TAV from V1 to V3 between the pCR patients and non-pCR patients. Statistical significance was defined as P < 0.05. Results: A significant decrease in the number of TAVs was observed during the NAST. In particular, the number of TAVs has a median (interquartile range) of 15 (7 - 24), 7 (3 - 14), and 2 (0 - 8) at V1, V2, V3, respectively, which are (pair-wise) significantly different (P < 0.01). Moreover, pCR patients showed a significantly greater decrease in the number of TAVs as compared to non-pCR patients. The percent changes in the number of TAVs from V1 to V3 have a median (range) of -88.89% (-100.00% - -60.00%) and -66.67% (-87.85% - -40.88%) in the pCR and non-pCR patients, respectively (P < 0.05). Conclusion: These preliminary results demonstrate that tumor-associated vasculature may be a valuable imaging biomarker for monitoring the response of TNBC to NAST. Ongoing efforts include additional investigation of the TAVs beyond their number, as well as applying the analysis to more patients. Citation Format: Chengyue Wu, Casey E. Stowers, Zhan Xu, Ernesto A. B. F. Lima, Clinton Yam, Jong Bum Son, Jingfei Ma, Gaiane M. Rauch, Thomas E. Yankeelov. Quantification of tumor-associated vasculature as an imaging biomarker for monitoring the response of triple-negative breast cancer to neoadjuvant chemotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5569.