Quantifying the Effects of Combination Trastuzumab and Radiation Therapy in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer

Simple Summary In vitro, combination trastuzumab and single-dose radiotherapy induces an additive effect. In vivo, combination trastuzumab and single-dose radiotherapy induces greater tumor kill than a higher single dose of radiotherapy, suggesting that combination therapy can be considered to achieve a similar reduction in tumor burden as traditional radiotherapy, with fewer adverse effects. Background: Trastuzumab induces cell cycle arrest in HER2-overexpressing cells and demonstrates potential in radiosensitizing cancer cells. The purpose of this study is to quantify combination trastuzumab and radiotherapy to determine their synergy. Methods: In vitro, HER2+ cancer cells were treated with trastuzumab, radiation, or their combination, and imaged to evaluate treatment kinetics. In vivo, HER2+ tumor-bearing mice were treated with trastuzumab and radiation, and assessed longitudinally. An additional cohort was treated and sacrificed to quantify CD45, CD31, alpha-SMA, and hypoxia. Results: The interaction index revealed the additive effects of trastuzumab and radiation in vitro in HER2+ cell lines. Furthermore, the results revealed significant differences in tumor response when treated with radiation (p < 0.001); however, no difference was seen in the combination groups when trastuzumab was added to radiotherapy (p = 0.56). Histology revealed increases in CD45 staining in tumors receiving trastuzumab (p < 0.05), indicating potential increases in immune infiltration. Conclusions: The in vitro results showed the additive effect of combination trastuzumab and radiotherapy. The in vivo results showed the potential to achieve similar efficacy of radiotherapy with a reduced dose when combined with trastuzumab. If trastuzumab and low-dose radiotherapy induce greater tumor kill than a higher dose of radiotherapy, combination therapy can achieve a similar reduction in tumor burden.

Automated summary

In vitro and in vivo studies have shown that combination trastuzumab and radiotherapy have an additive effect and can achieve similar efficacy as higher dose radiotherapy with fewer adverse effects. The combination therapy also showed potential in increasing immune infiltration.