Breast cancer (BC) is the leading
cancer in women worldwide.
Metastasis occurs in stage IV BC with bone and lung being common metastatic sites. Here we evaluate the effects of the
aromatase inhibitor letrozole on BC micro-metastatic
tumor growth in bone and lung
metastasis in intact and ovariectomized (OVX) mice with murine
estrogen receptor negative (ER-) BC cells inoculated in tibia. Forty-eight BALB/c mice were randomly assigned to one of four groups: OVX, OVX + Letrozole, Intact, and Intact + Letrozole, and injected with 4T1 cells intra-tibially.
Letrozole was subcutaneously injected daily for 23 days at a dose of 1.75 µg/g
body weight.
Tumor progression was monitored by bioluminescence imaging (BLI). Following necropsy, inoculated tibiae were scanned via µCT and bone response to
tumor was scored from 0 (no ectopic mineralization/
osteolysis) to 5 (extensive ectopic mineralization/
osteolysis). OVX mice had higher tibial pathology scores indicative of more extensive bone destruction than intact mice, irrespective of
letrozole treatment.
Letrozole decreased serum
estradiol levels and reduced lung surface
tumor numbers in intact animals. Furthermore, mice receiving
letrozole had significantly fewer
tumor colonies and fewer proliferative cells in the lung than OVX and intact controls based on H&E and Ki-67 staining, respectively. In conclusion, BC-inoculated OVX animals had higher tibia pathology scores than BC-inoculated intact animals and
letrozole reduced BC
metastases to lungs. These findings suggest that, by lowering systemic
estrogen level and/or by interacting with the host organ, the
aromatase inhibitor letrozole has the potential to reduce ER- BC
metastasis to lung.