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Pathways of Hormone Metabolism in Normal and Nonneoplastic Breast Tissue

The major pathway of steroid hormone biosynthesis from cholesterol is shown in FIGURE 1. This consists of the progressive removal of the carbon side chain of the D ring of C27 cholesterol to produce firstly C21 progestogens and then C19 androgens. The final step in the pathway is the removal of the carbon side chain between rings A and B resulting in C18 estrogens. This biosynthetic sequence was once considered to be unique to the gonads and placenta, but it is now realized that many of these transformations may also be performed by the breast. The evidence will therefore be reviewed that such biosynthesis and other interconversions within steroid classes occur in normal parenchyma, fibroadenomata, adipose tissue, and breast cysts/ fluids. Where appropriate, comparisons will be drawn with steroidogenesis in breast cancers which in general have been more extensively studied.