Accession Number : ADA550311


Title :   Chemoprevention of Breast Cancer by Mimicking the Protective Effect of Early First Birth


Descriptive Note : Final rept. 2 May 2005-2 May 2011


Corporate Author : UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES


Personal Author(s) : Pike, Malcolm


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a550311.pdf


Report Date : Jun 2011


Pagination or Media Count : 102


Abstract : We have shown in the rat that pregnancy, and also estradiol, estradiol plus progesterone, and beta-HCG are protective against mammary cancer; associated RNA expression changes have been identified. No definitive evidence was obtained of parity or hormonal prevention of mammary cancer in mice. Breast gene expression in parous and nulliparous women showed marked between-women differences but failed to distinguish parous from nulliparous women. ER and PR expression, and cell proliferation in the breast epithelium has been studied by immunohistochemistry in four protocols relating to chemoprevention: (1) parous and nulliparous women; (2) women in the first trimester of pregnancy; (3) women briefly exposed to high estrogen levels; and (4) women using oral contraceptives with markedly different progestin doses. Further studies are ongoing. Pregnancy reduced PRA expression and lower PRA distinguished parous from nulliparous women, but PRA was not affected by brief high level estrogen exposure. Reduced progestin failed to reduce breast proliferation. Stromal DNA methylation characterization of the parous and nulliparous samples has begun. Pregnancy reduces mammographic density and breast cancer risk. How these are related has been studied in a large autopsy series; results suggest that part of the protection may be the result of a reduction in breast epithelium; further studies of these samples are ongoing.


Descriptors :   *BIRTH , *BREAST CANCER , *CHEMOTHERAPY , *HORMONES , *PREVENTIVE MEDICINE , *RIBONUCLEIC ACIDS , AUTOPSY , CONTRACEPTION , DENSITY , EPITHELIUM , ESTROGENS , EXPOSURE(PHYSIOLOGY) , GENES , HISTOCHEMISTRY , IMMUNOCHEMISTRY , MAMMARY GLANDS , METHYLATION , MICE , ORAL INTAKE , RATS , RISK , SAMPLING , WOMEN


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE