Following initial regression, tumors of animals were growing by week. These mice were then assigned to the following three treatment groups: group continued on treatment with letrozole; group was given a secondline treatment with a higher dose of letrozole. The dose of tamoxifen used was chosen because in previous studies it caused optimal tumor growth suppression as firstline treatment. Tumors were measured weekly and tumor volumes were calculated.Linear mixedeffect models were used to estimate growth rate and average tumor volume and weight across treatment groups.Data on tumor volume were longitudinal and unbalanced.The duration of treatment varied across treatment groups.Mice receiving vehicle were sacrificed at week, receiving fulvestrant alone at week; animals in the remaining Thujone groups were treated until week. For tumor volume, diagnostic plots suggested that models of exponential growth were appropriate to the data.Therefore, linear mixedeffect models were fit to the natural logarithm of tumor volume over time.This approach allows the estimation of an exponential variable controlling the tumor growth rate for each treatment group.Responses from different animals were assumed to be statistically independent whereas those within an animal were correlated.Via model diagnostics, the firstorder autoregressive covariance structure was chosen as the most appropriate for the data.Weight of the multiple tumors per subject and uterine weight were obtained for each mouse after it was sacrificed.These animals were sacrificed at week due to large tumor size, and the estimated mean tumor weight was. Fulvestrant treated tumors were static for the first weeks of treatment.Thereafter, these tumors started to proliferate and had doubled after weeks of treatment. At week, tumor volumes were significantly larger in the group treated with fulvestrant alone compared with letrozole. Also, treatment with letrozole plus fulvestrant was superior to fulvestrant alone. Fulvestranttreated mice were sacrificed at week due to large tumor size.Mice receiving fulvestrant had significantly smaller uteri. These data indicate that fulvestrant can effectively block the uterotropic activity of estrogens produced by peripheral aromatization of androstenedione.In the present study, tumor volume was reduced by over the first weeks of treatment.These tumors slowly returned to their initial size after weeks and had doubled their initial volume after weeks of treatment. Treatment with the combination of letrozole plus fulvestrant also caused an initial regression of tumors, but was able to maintained tumor growth inhibition by over weeks of treatment or tamoxifen on tumors proliferating during letrozole treatment compared with the combination of letrozole plus fulvestrant.As the tumors started to proliferate during letrozole were assigned to three different groups so that there was no difference in total tumor volume across these groups.One group of mice continued on treatment with letrozole; another group received secondline treatment with a higher dose of letrozole. The tumor growth rate over weeks was compared across the following four groups: letrozole plus fulvestrant. The experiment was terminated at week when tumor volumes and weights, as well as uterine weights, were measured.Letrozole alone for weeks was less effective than letrozole plus fulvestrant in controlling tumor growth on week. Also, tumor volumes were statistically significantly larger in the letrozole treatment group than in the combination, was not effective after letrozole treatment.

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