Prophylactic cranial irradiation reduces the incidence of brain metastasis in a mouse model of metastatic, HER2-positive breast cancer
Daniel L. Smith1,3, Bisrat G. Debeb1,3, Parmeswaran Diagaradjane1, Richard Larson1,3, Swaminathan Kumar1,3,4, Jing Ning2, Lara Lacerda1,3, Li Li1,3, Wendy A. Woodward1,3
1Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
2 Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
3 ScMorgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, TX, USA
4 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA
Correspondence:
Wendy A. Woodward, email:[email protected]
Keywords: prophylactic cranial irradiation; brain metastasis; breast cancer; PCI
Received: November 11, 2020 Accepted: January 21, 2021 Published: March 13, 2021
Abstract
Prophylactic cranial irradiation (PCI) can reduce the incidence of brain metastasis and improve overall survival in some patients with acute lymphoblastic leukemia or small-cell lung cancer. We examined the potential effects of PCI in a mouse model of breast cancer brain metastasis. The HER2+ inflammatory breast cancer cell line MDA-IBC3 was labeled with green fluorescent protein and injected via tail-vein into female SCID/Beige mice. Mice were then given 0 Gy or 4 Gy of whole-brain irradiation 2 days before tumor-cell injection or 5 days, 3 weeks, or 6 weeks after tumor-cell injection. Mice were sacrificed 4-weeks or 8-weeks after injection and brain tissues were examined for metastasis by fluorescent stereomicroscopy. In the unirradiated control group, brain metastases were present in 77% of mice at 4 weeks and in 90% of mice at 8 weeks; by comparison, rates for the group given PCI at 5 days after tumor-cell injection were 20% at 4 weeks (p=0.01) and 30% at 8 weeks (p=0.02). The PCI group also had fewer brain metastases per mouse at 4 weeks (p=0.03) and 8 weeks (p=0.006) versus the unirradiated control as well as a lower metastatic burden (p=0.01). Irradiation given either before tumor-cell injection or 3-6 weeks afterward had no significant effect on brain metastases compared to the unirradiated control. These results underscore the importance of timing for irradiating subclinical disease. Clinical whole brain strategies to target subclinical brain disease as safely as possible may warrant further study.
