Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments.
BACKGROUND
Women who have undergone a full-term pregnancy before the age of 20 have one-half the risk of developing breast cancer compared with women who have never gone through a full-term pregnancy. This protective effect is observed universally among women of all ethnic groups. Parity in rats and mice also protects them against chemically induced mammary carcinogenesis.


METHODS
Seven-week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the rats were treated with natural or synthetic estrogens and progestins for 7-21 days by subcutaneous implantation of silastic capsules.


RESULTS
In our current experiment, we demonstrate that short-term sustained exposure to natural or synthetic estrogens along with progestins is effective in preventing mammary carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for 3 weeks significantly reduced the incidence of mammary cancer. Short-term exposure to ethynyl estradiol plus megesterol acetate or norethindrone was effective in decreasing the incidence of mammary cancers. Tamoxifen plus progesterone treatment for 3 weeks was able to confer only a transient protection from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was effective in conferring protection against mammary cancers.


CONCLUSIONS
The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations.
Rajkumar
Lakshmanaswamy
L
Department of Molecular and Cell Biology and the Cancer Research Laboratory, University of California, Berkeley, California, USA. rajkumar@uclink4.berkeley.edu
Guzman
Raphael C
RC
Yang
Jason
J
Thordarson
Gudmundur
G
Talamantes
Frank
F
Nandi
Satyabrata
S
D000077584:2-Methoxyestradiol; D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004964:Estriol / Q000008:administration & dosage; D004967:Estrogens / Q000008:administration & dosage; D004997:Ethinyl Estradiol / Q000008:administration & dosage; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced / Q000517:prevention & control*; D019290:Megestrol Acetate / Q000008:administration & dosage; D008770:Methylnitrosourea / Q000633:toxicity; D009640:Norethindrone / Q000008:administration & dosage; D011374:Progesterone / Q000008:administration & dosage; D011372:Progestins / Q000008:administration & dosage; D051381:Rats; D011917:Rats, Inbred Lew; D013629:Tamoxifen / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
D000477:Alkylating Agents; D004967:Estrogens; D011372:Progestins; D013629:Tamoxifen; D004997:Ethinyl Estradiol; D011374:Progesterone; D004958:Estradiol; D008770:Methylnitrosourea; D000077584:2-Methoxyestradiol; C001390:2-hydroxyestradiol; D004964:Estriol; D009640:Norethindrone; D019290:Megestrol Acetate