TABLE 1.

Summary of studies that have examined the impact of the vitamin D pathway in transgenic models of breast cancer.

Model	Study Description	Outcome	Reference
bLHβ-CTP mice: Mammary hyperplasia and spontaneous tumors develop in response to chronic, systemic LH production	Effect of short term treatment of tumor bearing mice with EB1089 on proliferation and tumor burden.	LH-driven tumors had high Vdr expression. EB1089 inhibited tumor cell proliferation and reduced tumor burden in ~50% of treated mice.	Milliken et al, 2002 (23)
MMTV-Neu mice: Mammary tumors develop in response to targeted expression of Neu oncogene (models HER2 positive human breast cancer)	MMTV-Neu mice were crossed with Vdr null mice. Ductal morphology, pre-neoplastic lesions and tumor burden were evaluated.	High expression of Vdr in MMTV-Neu tumors and lung metastatic foci. Abnormal ductal morphology in Vdr-null and Vdr-Het mice. . Increased tumor incidence in Vdr-Het vs. Vdr-WT mice on MMTV-Neu background.	Zinser et al, 2004 (26)
	MMTV-Neu mice were treated with VDR agonist BXL0124	BXL0124 decreased tumor weight, incidence and multiplicity and inhibited ErbB2, Erk and Akt signaling.	Lee et al, 2010 (24)
	MMTV-Neu mice were treated with BXL0124 ± CDDO-Im (synthetic triterpenoid) either before or after tumor onset.	In prevention protocol, both BXL0124 and CDDO-Im delayed tumor development but the combination was most effective. In the therapeutic protocol, administration of the combination did not reduce tumor burden.	So et al, 2013 (22)
MMTV-Ron mice: Metastatic mammary tumors develop in response to Ron oncogene expression.	MMTV-Ron mice were crossed with Vdr null mice. Hyperplasia, tumor burden and β-catenin signaling were evaluated.	Vdr deletion enhanced Ron-mediated mammary hyperplasia, tumor burden and metastasis to lungs and liver. β-catenin signaling was elevated in Vdr ablated tumors.	Johnson et al, 2015 (25)
MMTV-PyMT mice: Rapid onset mammary tumors that metastasize to lung. Develop in response to targeted expression of polyoma middle T antigen.	Tumorigenesis was evaluated in MMTV-PyMT mice fed low (25IU/kg) vs standard (1000IU/kg) vitamin D diets and in mice perfused with 25D or 1,25D. Tumor vitamin D metabolites were measured.	Low dietary vitamin D accelerated tumorigenesis relative to standard diet. Systemic perfusion with 25D or 1,25D delayed tumorigenesis and decreased lung metastasis. Both 25D and 1,25D were detected in tumors.	Rossdeutscher et al, 2015 (28)
	Tumor development was evaluated in MMTV-PyMT mice with mammary-specific deletion of Cyp27b1.	Targeted ablation of Cyp27b1 in MMTV-PyMT mice accelerated mammary hyperplasia and tumorigenesis. NfKB and JAK-STAT signaling were increased in Cyp27b1 ablated tumors. Cyp27b1 ablation reduced tumor 1,25D level.	Li et al, 2016 (27)