TY - JOUR
T1 - Tamoxifen suppresses histologic progression to atypia and DCIS in MCFIOAT xenografts, a model of early human breast cancer
AU - Visscher, D. W.
AU - Nanjia-Makker, P.
AU - Heppner, G.
AU - Shekhar, P. V.M.
N1 - Funding Information:
Supported by grants from the US Army Medical Research and Material Command (DAMD17-94-J-4427, PVMS), the National Institute of Health (CA 60881, PVMS; CA 22453, Cancer Center Support Grant).
PY - 2001
Y1 - 2001
N2 - We evaluated the effects of tamoxifen on the growth and progression of MCFIOAT xenografts, an estrogen responsive model of human breast tumor progression, in which cells are injected orthotopically into the mammary fat pad of female nude mice. At 10 weeks following implantation, histologic sections of each graft were evaluated microscopically for histologic lesions analogous to human breast tumor progression, graded as simple hyperplasia, complex hyperplasia, atypical hyperplasia, ductal carcinoma in situ and invasive carcinoma. Three out of five xenografts in (endocrine intact) control animals progressed to atypical hyperplasia, one progressed to ductal carcinoma in situ and one to invasive carcinoma. The latter two control grafts also contained foci of putative precursor lesions (i.e. atypical hyperplasia and in situ carcinoma, respectively). Tamoxifen supplemented xenografts (N = 17) were uniformly smaller than controls, but contained invasive carcinoma in a similar proportion (4/17, 24%). However, none of these grafts exhibited ductal carcinoma in situ and only one contained atypical hyperplasia. Most grafts in tamoxifen supplemented animals (10/17, including all four with carcinomas) showed complex hyperplasia, which typically dominated the graft. We conclude that tamoxifen selectively inhibits the appearance or growth of preinvasive index lesions. Development of malignancy in the absence of such precursors, though, implies selection for alternative histogenetic pathways as a result of endocrine manipulation.
AB - We evaluated the effects of tamoxifen on the growth and progression of MCFIOAT xenografts, an estrogen responsive model of human breast tumor progression, in which cells are injected orthotopically into the mammary fat pad of female nude mice. At 10 weeks following implantation, histologic sections of each graft were evaluated microscopically for histologic lesions analogous to human breast tumor progression, graded as simple hyperplasia, complex hyperplasia, atypical hyperplasia, ductal carcinoma in situ and invasive carcinoma. Three out of five xenografts in (endocrine intact) control animals progressed to atypical hyperplasia, one progressed to ductal carcinoma in situ and one to invasive carcinoma. The latter two control grafts also contained foci of putative precursor lesions (i.e. atypical hyperplasia and in situ carcinoma, respectively). Tamoxifen supplemented xenografts (N = 17) were uniformly smaller than controls, but contained invasive carcinoma in a similar proportion (4/17, 24%). However, none of these grafts exhibited ductal carcinoma in situ and only one contained atypical hyperplasia. Most grafts in tamoxifen supplemented animals (10/17, including all four with carcinomas) showed complex hyperplasia, which typically dominated the graft. We conclude that tamoxifen selectively inhibits the appearance or growth of preinvasive index lesions. Development of malignancy in the absence of such precursors, though, implies selection for alternative histogenetic pathways as a result of endocrine manipulation.
KW - Atypical hyperplasia
KW - Breast carcinoma
KW - Fibrocystic change
KW - Tamoxifen
KW - Xenograft model
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U2 - 10.1023/A:1006490000659
DO - 10.1023/A:1006490000659
M3 - Article
C2 - 11245338
AN - SCOPUS:0035116008
SN - 0167-6806
VL - 65
SP - 41
EP - 47
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -