Abstract 2775: Her2 expression level is positively correlated with paclitaxel response in human breast cancer xenograft mouse model
Authors: Lu Yun , Massicano Adriana I. , Lapi Suzanne E. , Li Meng , Song Patrick N. , Sorace Anna G. 
Published: September 2020

Introduction: The overall goal of this study is to quantify amount and heterogeneity of Her2 expression and determine if its expression affects its response to chemotherapy in breast cancer. Paclitaxel (PTX) is one of the most commonly used first-line drugs in the treatment of breast cancer. However, it is reported that overall PTX response rate is 30%-60%, as first-line treatment of metastatic breast cancer, and the main treatment failure is PTX resistance. Thus, novel discoveries of molecular mechanisms that account for ineffective response or resistance to chemotherapy is critical in breast cancer treatment. This study evaluates whether Her2 expression level is correlated with PTX treatment efficacy in a controlled pre-clinical mouse model.

Experimental Design: BT474 (1 × 107) or MDA-MB-231 (2 × 106) cells were subcutaneously injected into athymic nude mice (n = 10). Mice were enrolled in the study once they achieved tumor volume of 200 mm3. Tumor size were measured with caliper weekly or every 3 days after experiment started. In vivo Her2 expression level was determined by [89Zr]-Pertuzumab (Her2 antibody) positron emission tomography/computed tomography (PET/CT) imaging at one week prior to initiation of treatment. PTX (15 mg/kg) was administrated via i.v. at day 0 and day 3. In vivo tumor metabolism was quantified by 2-deoxy-2-[fluorine-18]fluoro- D-glucose ([18F]-FDG) PET/CT imaging at day 0, day 3 and day 6. Mean, standard deviation, and frequency histogram of standard uptake value (SUV) was quantified. Tumors were harvested at day 6 for histological analysis. Pearson's correlation test was used as statistical analysis.

Results: BT474 (Her2+) tumors had significantly increased [89Zr]-Pertuzumab uptake compared to MDA-MB-231 (Her2-) tumors, which indicated the specificity and accuracy of [89Zr]-Pertuzumab PET/CT imaging. [89Zr]-Pertuzumab SUV varies within BT474 tumors, and tumor growth rate was positively correlated with mean Her2 expression (R2=0.9011, p=0.001). During PTX treatment, tumor volumes did not reveal significant changes. However, [18F]-FDG SUV concentration, normalized to percent changes from day 0 to day 3, was negatively correlated with initial [89Zr]-pertuzumab SUV concentration (R2=0.3654, p=0.05).

Conclusion: Preliminary results show Her2 expression level is positively correlated with chemotherapy response in mouse models of human breast cancer. This discovery will help studies of PTX resistance in breast cancer and potentially guide clinical administration of combined therapies. [89Zr]-Pertuzumab PET/CT imaging quantitively measured Her2 expression level in vivo, and [18F]-FDG PET/CT imaging revealed the early signals of drug treatment efficacy.

Citation Format: Yun Lu, Adriana I. Massicano, Suzanne E. Lapi, Meng Li, Patrick N. Song, Anna G. Sorace. Her2 expression level is positively correlated with paclitaxel response in human breast cancer xenograft mouse model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2775.