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Development of a clinically relevant breast cancer model using retro-orbital paclitaxel and subcutaneous estradiol
Egro FM, Johngrass M, Ejaz A, Camison L, Marra K, Kokai L, Rubin JP
University of Pittsburgh
2018-02-26
Presenter: Francesco M. Egro MBChB, MSc, MRCS
Affidavit:
Vu T. Nguyen
Director Name: Vu T. Nguyen
Author Category: Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: Breast (Aesthetic and Recon.)
Background: Approximately 1 in 8 U.S. women develop invasive breast cancer over the course of their lifetime. A reliable and relevant breast cancer animal model is needed to develop future therapies. This study developed a NOD-SCID mouse breast cancer model to study the effect of paclitaxel injection on MCF-7 human breast cancer cells origin tumor development.
Methods: An IACUC approved study was conducted at the University of Pittsburgh in 2017. An appropriate dose and frequency of paclitaxel demonstrating no lethality was assessed in 10 BALB/c mice by injecting 14 mg/kg weekly or biweekly over 8 weeks. Subsequently, 1 × 106 MCF-7 tumor cells suspended in matrigel were inoculated into four mammary fat pads of 15 NOD-SCID mice. Inoculated mice were divided into groups of five and were treated with either 0.18 mg/kg subcutaneous estradiol pellet (positive control for tumor development), 14 mg/kg retro-orbital paclitaxel (treatment group), or not treated at all. Mice were sacrificed at 8 weeks, and tumor size, volume and weight were calculated.
Results: BALB/c mice thrived demonstrating that weekly retro-orbital injections are a safe/effective delivery method of 14mg/kg paclitaxel dose. Treatment of NOD-SCID mice with paclitaxel resulted in a statistical significant reduction of tumor growth compared to no treatment and estrogen treated group, which demonstrated the largest tumor volume at 8 week timepoint (tumor & paclitaxel = 15.3 mm3, tumor alone = 81.4 mm3, tumor & estrogen = 115.8 mm3, p<0.001).
Conclusion: A reliable breast cancer animal model was established using retro-orbital paclitaxel and subcutaneous estradiol.
