Tamoxifen suppresses histologic progression to atypia and DCIS in MCFIOAT xenografts, a model of early human breast cancer

We evaluated the effects of tamoxifen on the growth and progression of MCFI OAT xenografts, an estrogen responsive model of human breast tumor progress ion, 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 analogo us to human breast tumor progression, graded as simple hyperplasia, complex hyperplasia, atypical hyperplasia, ductal carcinoma in situ and invasive c arcinoma. Three out of five xenografts in (endocrine intact) control animal s progressed to atypical hyperplasia, one progressed to ductal carcinoma in situ and one to invasive carcinoma. The latter two control grafts also con tained 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 du ctal carcinoma in situ and only one contained atypical hyperplasia. Most gr afts in tamoxifen supplemented animals (10/17, including all four with carc inomas) showed complex hyperplasia, which typically dominated the graft. We conclude that tamoxifen selectively inhibits the appearance or growth of p reinvasive index lesions. Development of malignancy in the absence of such precursors, though, implies selection for alternative histogenetic pathways as a result of endocrine manipulation.