The observation that chemically induced
breast cancer is prevented when the mammary gland is completely differentiated by a full term pregnancy prior to exposure to a
carcinogen, led us to test the hypothesis that synthetic ovarian
hormones commonly used for the purpose of
contraception might drive mammary gland differentiation enough to be protective from
carcinogen--induced neoplastic transformation. This hypothesis was only partially proven, due to the unexpected finding that a high dose of the
progestagenic agent medroxyprogesterone acetate (MPA), increased
tumor incidence, whereas a similar dose of the mostly estrogenic
norethynodrel--
mestranol (NM) was protective. An additional finding was the fact that these two agents exerted a different action on thoracic than on abdominal mammary glands. MPA inhibited differentiation of TEBs in the former, but stimulated lobule development in the latter. This difference in response seemed to be associated to the asynchronous development of the mammary glands located in different topographic regions. These observations indicated that the response of the mammary gland epithelium with either differentiation or cell proliferation is in great part modulated by the condition of the target organ. Although the concept of
hormone prevention of
breast cancer promises to be an achievable goal, there are still basic fundamental questions that need to be answered. First, how do
estrogens and
progesterone act on the mammary epithelium, second, what is the sequence in which they act on the mammary gland in order to induce differentiation of the organ, third, why the same homonal milieu in a single animal results in asynchronous development of glands located in thoracic versus those in the abdominal region.