Mammographic breast density and postmenopausal hormone therapy

Breast cancer is the most frequent malignancy among women in the western world. More than one million women are estimated to be diagnosed with the disease every year. The breast is a target organ for sex steroids and hormonal treatments have been found to increase the risk for breast cancer. Still basic knowledge about the effects of hormonal therapy on the normal postmenopausal breast is very poor. Mammographic breast density is a radiological phenomenon; the mammographic picture of the breast varies according to the relative amounts of fat, connective and epithelial tissues. Each type of breast tissue is different as regards its translucency for x-rays. Increased mammographic breast density has been established as a strong and independent risk factor for breast cancer. The biologic characteristics of dense breast tissue have not yet been defined. The aims of this work were to compare the effects on breast density of different estrogen/progestogen regimens and to evaluate alternative treatments in postmenopausal women. Furthermore to investigate the expression of Syndecan-1 and estrogen receptor subtypes in dense and non-dense breast tissue. Mammographic breast density was found to be markedly increased in 30-50% of women using continuous combined estrogen/progestogen treatment. In contrast, unopposed systemic estrogen, low dose estrogen, tibolone and a low dose intrauterine progestogen system in combination with oral estrogen had only little impact on breast density. Possibly a further reduction of the progestogen dose could develop into an alternative with a minimal or even neutral effect on the breast. There was a high correlation between data based digitized quantification of mammographic breast density and the traditional visual classifications. Mammographic density should be regarded as a continuous variable and the digitized method allows a more sensitive measurement. The increase in mammographic density when it occurs is a rapid event and is fully established already during the first few months of therapy. Thereafter density remains stable during prolonged treatment with the same regimen. An increase in density may be associated with subjective symptoms of discomfort and pain. The major component of breast tissue is stroma. Epithelial proliferation can not explain the physical and dynamic features of breast density. In surgical specimens of radiologically dense and histologically normal breast tissue there was an increased expression of the proteoglycan Syndecan-1 in all tissue compartments. The interaction between epithelium and stroma in response to hormones is of major importance both for normal breast development as well as in carcinogenesis and tumor progression. An increase of Syndecan-1 and possibly other stromal proteoglycans may be a characteristic feature of dense breast tissue. An increase in mammographic breast density and breast cell proliferation should be regarded as an unwanted and potentially hazardous side-effect during hormonal therapy. Efforts should be made to define treatment regimens for postmenopausal women that have a minimum of effects on the breast but still maintain the many advantages of conventional hormone therapy. In the future information regarding breast density should be a part of clinical management in women receiving hormonal treatment