Estrogen and Progesterone Receptors in Benign Breast Epithelium

Abstract

: Estrogen and progesterone are necessary for lobulo-alveolar development of the human breast, and there is an abundance of epidemiologic literature implicating estrogen and possibly progesterone exposure as promoters of breast malignancy. The investigation of estrogen receptor (ER) and progesterone receptor (PgR) distribution in normal and benign breast tissue may be a measure of susceptibility of the tissue to these hormones. Earlier data from radioligand binding assays showed that benign breast tissue expressed little or no ER; newer immunohistochemical (IHC) methods have led to the investigation of benign breast tissue from at least 1243 women in 12 studies in the last 9 years. These show that the level of expression of ER and PgR in normal breast epithelium is significantly lower than in receptor positive carcinomas. Immunostaining patterns for both receptors show a great deal of heterogeneity. There is general agreement that stromal and myoepithelial cells are negative for both ER and PgR. A growing body of evidence suggests that PgR is the dominant sex steroid receptor in the normal breast. Mean values for PgR positive cells in breast epithelium range from 24% to 29%; ER is positive by IHC in 3% to 15.6% of normal breast epithelial cells. No firm conclusions are possible as yet regarding overexpression in proliferative epithelium. There is agreement that the proportion of ER positive cells declines in the second half of the menstrual cycle, but there is no clear cut relationship between PgR positivity with the menstrual cycle. Oral contraceptive use appears to decrease the proportion of ER positive cells, and increase mammary epithelial proliferation. A recent case-control analysis of epithelial ER and PgR status reports an association of ER positive benign epithelium with the presence of cancer in the breast. Future research should include a systematic quantitative analysis of receptor expression in epithelial proliferative lesions, and the longitudinal follow-up of women who have had receptor testing on benign breast tissue.