New hormone-related markers of high risk to breast cancer.

New markers of increased risk to breast cancer are examined and related to established risk markers. The following new evidence is highlighted: (1) Increased testosterone secretion by the ovaries is currently the only major steroid abnormality shown to be associated with increased risk of both premenopausal and postmenopausal breast cancer. (2) Upper body-type obesity is a marker for both hyperandrogenaemia and hyperinsulinaemia and is associated with an increased risk of breast cancer. Upper body type obesity may already be recognised in early puberty in caucasian girls and is associated with a characteristic androgen/oestrogen profile. (3) Relative tallness in women is associated with an increased risk of breast cancer. A hypothesis is offered on the significance of these markers in the aetiology of mammary cancer in women, and also a means of testing the hypothesis. The hormonal promotion of mammary carcinogenesis is likely to be greatest between puberty and the first full term pregnancy. The presence of hyperinsulinaemia can increase the ovarian production of androgen, and the abnormal hormonal profile may stimulate proliferative activity in mammary epithelium. This may increase the risk of epithelial atypia and carcinogenesis.