PURPOSE: The aromatase inhibitors @entity4672 and @entity13558 have been approvedrecently as first-line treatment options for hormone-dependent @entity0 . Although it is established that a proportion of @entity1 who relapse on first-line @entity440 therapy show additional responses to aromatase inhibitors, it has not been determined whether @entity5 that acquire resistance to aromatase inhibitors in the first line remain sensitive to second-line therapy with antiestrogens. The aim of this study was to determine whether aromatase-transfected and hormone-dependent MCF-7Ca @entity1 @entity0 cells remain sensitive to antiestrogens after: (a) long-term growth in @entity134 -depleted medium in vitro; and (b) long-term treatment with the aromatase inhibitor @entity4672 in vivo. METHODS: In the first approach, a variant of the MCF-7Ca @entity1 @entity0 cell line was selected that had acquired the ability to grow in @entity172 -depleted medium after 6-8 months of culture. @entity134 -deprived UMB-1Ca cells were analyzed for aromatase activity levels, @entity5282 levels, and sensitivity to @entity172 and antiestrogens in vitro and in vivo. In the second approach, established MCF-7Ca @entity0 xenografts were treated with @entity4672 10 microg/day for 12 weeks followed by 100 microg/day for 25 weeks until @entity5 acquired the ability to proliferate in the presence of the drug. Long-term @entity4672 -treated @entity5 were then transplanted into new @entity19 , and the effects of antiestrogens and aromatase inhibitors on @entity5 growth were determined. RESULTS: @entity134 -deprived UMB-1Ca @entity0 cells continued to express aromatase activity at levels comparable with the parental cell line. However, compared with MCF-7Ca cells, UMB-1Ca cells expressed elevated levels of functionally active @entity172 receptor. The growth of UMB-1Ca cells in vitro was inhibited by the antiestrogens @entity440 and faslodex and @entity5 growth in vivo was inhibited by @entity440 . In the second approach, the time for MCF-7Ca @entity5 xenografts to approximately double in volume after being treated sequentially with the increasing doses of @entity4672 was thirty-seven weeks. Long-term @entity4672 -treated @entity5 continued to express functionally active aromatase. When transplanted into new @entity19 , growth of the long-term @entity4672 -treated @entity5 was slowed by @entity440 and inhibited more effectively by faslodex. @entity5 growth was refractory to the aromatase inhibitors @entity13558 and @entity19836 but, surprisingly, showed sensitivity to @entity4672 . CONCLUSIONS: @entity134 -deprived UMB-1Ca @entity1 @entity0 cells selected in vitro and long-term @entity4672 -treated MCF-7Ca @entity0 xenografts remain sensitive to second-line therapy with antiestrogens and, in particular, to faslodex. This finding is associated with increased expression of functionally active @entity172 receptor after @entity134 -deprivation of MCF-7Ca @entity1 @entity0 cells in vitro.

The effect of second-line antiestrogen therapy on @entity0 growth after first-line treatment with the aromatase inhibitor XXXX : long-term studies using the intratumoral aromatase postmenopausal @entity0 model.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity172 :: ('MESH:D004967', 'Chemical') :: ['estrogen', 'estrogens'] @entity4672 :: ('MESH:C067431', 'Chemical') :: ['letrozole'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer', 'breast tumor', 'advanced breast cancer'] @entity440 :: ('MESH:D013629', 'Chemical') :: ['tamoxifen'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Tumor', 'tumors'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity134 :: ('CHEBI:35341', 'Chemical') :: ['Steroid', 'steroid'] @entity19836 :: ('MESH:C014594', 'Chemical') :: ['formestane'] @entity13558 :: ('MESH:C090450', 'Chemical') :: ['anastrozole'] @entity5282 :: ('3164', 'Gene') :: ['hormone receptor']
@entity4672 :: (MESH:C067431,Chemical) :: ['letrozole']
