Expression of sex steroid receptors and IGF-1 mRNA in breast tissue - effects of hormonal treatment

The mechanisms behind increased breast tissue proliferation and a possibly increased breast cancer risk in women using hormonal contraception (HC) and hormonal replacement therapy (HRT) are incompletely understood. We analyze d breast tissue from 20 premenopausal and seven postmenopausal women underg oing reduction mammoplasties for estrogen receptor (ER) and progesterone re ceptor (PR) content as well as mRNA levels for ER, PR and insulin-like grow th factor-1 (IGF-1). The receptor values were correlated to IGF-1 mRNA conc entrations and levels of steroid and peptide hormones and SHBG. In women us ing HC, we found significantly lower ER values (p = 0.02) but non-significa ntly lower ER mRNA levels compared to those in naturally cycling women. PR and PR mRNA were no different. Women on HC displayed a higher breast tissue proliferation (p = 0.05) expressed as Ki-67, MIB-1 positivity, which was c orrelated with IGF-I mRNA (r(s)=0.82, p = 0.04). Since the concentration of sex steroid receptors in breast tissue is comparatively low and steroid re ceptors are down-regulated during hormonal treatment, mechanisms other than direct sex steroid receptor action are likely to be present. Our results s uggest a role for IGF-1 in the proliferative response of breast tissue duri ng exogenous hormonal treatment. (C) 1999 Elsevier Science Ltd. All rights reserved.