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An estimated one third of all American and United Kingdom women take hormone therapy. In sharp contrast to these numbers, as many as one half of women diagnosed with breast cancer have taken hormones. Little additional information is available regarding the risk of breast cancer and even less is known about the association between hormone therapy and fibrocystic (FCD) disease or atypia of the breast. Three hundred women between 30 and 50 years of age were enrolled in this study, including 120 taking hormone replacement (HRT) therapy and 180 women who had never taken hormone therapy. These women were divided into four categories including those with normal breast tissue, those with FCD disease, those with cellular atypia, and those with breast cancer. Another group of women were also identified who had breast implants. Using breast enhanced scintigraphy (BEST) imaging, changes in breast tissue were determined and compared according to the use of HRT. Forty percent (122 of 300) had "normal" breasts, of whom 68.8% (84 of 122) did not take HRT. This accounted for 46.7% (84 of 180) of the women not taking hormone therapy, while only 31.7% (38 of 120) of the women taking HRT had normal breasts. This difference was statistically (p.001) significant. There was a greater incidence of breast abnormality in women taking HRT and a lower incidence in pathology among women not taking HRT when cumulatively analyzed for FCD, cellular atypia, and breast cancer. This difference was statistically significant (p.001) for women with breast cancer where 62.5% (10 of 16) were women taking HRT. Although the study was relatively small, it is the first such study to compare a continuum of changes in breast tissue according to the use of HRT. The study suggests that the initial empirical observations regarding higher incidence of HRT among women with breast cancer, may have a relationship to underlying changes in breast tissue that are associated with differences in mitochondrial content and activity. Further investigation is needed. [ABSTRACT FROM AUTHOR]