Hormone-Induced Protection of Mammary Tumorigenesisin Genetically Engineered Mouse Models - Genetic Engineering: Recent Developments in Applications - page 267

Results
In the p53-null mammary transplant model, a 2-week exposure to estrogen
and progesterone during the immediate post-pubertal stage (2 to 4 weeks after
transplantation) of mammary development decreased mammary tumorigene-
sis by 70 to 88%. At 45 weeks after transplantation, analysis of whole mounts
of the mammary outgrowths demonstrated the presence of premalignant hy-
perplasias in both control and hormone-treated glands, indicating that the
hormone treatment strongly affects the rate of premalignant progression. One
possible mechanism for the decrease in mammary tumorigenesis may be an al-
tered proliferation activity as the bromodeoxyuridine labeling index was de-
creased by 85% in the mammary glands of hormone-treated mice. The same
short-term exposure administered to mature mice at a time of premalignant
development also decreased mammary tumorigenesis by 60%. A role for stro-
ma and/or systemic mediated changes induced by the short-term hormone (es-
trogen/progesterone) treatment was demonstrated by an experiment in which
the p53-null mammary epithelial cells were transplanted into the cleared
mammary fat pads of previously treated mice. In such mice, the tumor-pro-
ducing capabilities of the mammary cells were also decreased by 60% com-
pared with the same cells transplanted into unexposed mice. In the second set
of experiments using the activated Her-2/neu transgenic mouse model, short-
term estradiol or estradiol plus progesterone treatment decreased mamma-
ry tumor incidence by 67% and 63%, and tumor multiplicity by 91% and
88%, respectively. The growth rate of tumors arising in the hormone-treated
activated Her-2/neu mice was significantly lower than tumors arising in non-
hormone treated mice.
Conclusion
Because these experiments were performed in model systems that mimic many
essential elements of human breast cancer, the results strengthen the rationale
for translating this prevention strategy to humans at high risk for developing
breast cancer.
introduction
It has long been recognized that hormones have an intimate and decisive role in
the development and progression of mammary tumorigenesis. The earliest treat-
ment for prevention of breast tumor recurrence in humans (published in 1896)
was removal of the ovaries, the source of the reproductive hormones estrogen and
progesterone [1]. The most efficacious treatment for the prevention of recurrence
in modern therapy for breast cancer is treatment with drugs that target the estrogen